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2004 PROGRAM

Friday & Saturday May 7 – 8, 2004

The Hyatt Hotel Sacramento, California

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Board Members

President Marian Sigman, PhD University of California, Los Angeles Vice President Sally Rogers, PhD University of California, Davis MIND Institute Treasurer Edwin Cook, MD University of Chicago Secretary Diane Chugani, PhD Wayne State University Program Chair Nancy Minshew, MD University of Pittsburgh Medical Center Membership Chair Robert Schultz, PhD Yale University Nominations Chair Joseph Piven, MD University of North Carolina Chapel Hill Publications Chair David Amaral, PhD University of California, Davis MIND Institute Member at Large Ricki Robinson, MD Descanso Medical Center for Development and Learning

Program Committee David Amaral University of California, Davis MIND Institute Anthony Bailey Oxford University Grace Baranek University of North Carolina at Chapel Hill Simon Baron-Cohen Cambridge University Marlene Behrmann Carnegie Mellon University Susan Bookheimer University of California, Los Angeles Dermot Bowler City University Marie Bristol-Power Jacob Burak McGill University Tony Charman University College London Diane Chugani Wayne State University/ Children’s Hospital of Michigan Edwin Cook University of Chicago Christina Corsello University of Michigan

Linda Daly Petrus de Vries Cambridge University Glen Dunlap University of South Florida Deborah Fein University of Connecticut Eric Fombonne McGill University Christopher Gillberg Hill Goldsmith University of Wisconsin Robin Hansen University of California, Davis Sandra Harris Rutgers University Robert Hendren University of California, Davis Susan Hyman University of Rochester Bob Joseph Boston University School of Medicine Marcel Just Carnegie Mellon University Connie Kasari University of California, Los Angeles

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Chantal Kemner University Medical Centre, The Netherlands Ami Klin Yale University Patricia Krantz Princeton Child Development Institute Nick Lange Harvard University Ian Lipkin Columbia University Eric London National Alliance for Autism Research (NAAR) Cathy Lord University of Michigan Luna Beatrice University Pittsburgh Medical Center William McMahon The University of Utah Nancy Minshew University of Pittsburgh School of Medicine Laurent Mottron Clinique Specialisee de L’autisme Peter Mundy University of Miami Sam Odom Indiana University

Sally Ozonoff University of California, Davis Issac Pessah University of California, Davis Jane Pickett Autism Tissue Program ~The Gift Joseph Piven University of North Carolina Ricki Robinson Keck School of Medicine of USC Sally Rogers University of California, Davis MIND Institute Laura Schreibman University of California, San Diego Robert Schulz Yale Child Study Center Andy Shih National Alliance for Autism Research (NAAR) Marian Sigman University of California, Los Angeles Tristram Smith University of Rochester Medical Center Anne Spence University of California, Irvine Wendy Stone Vanderbilt Children’s Hospital

Helen Tager-Flusberg Boston University Fred Volkmar Yale Child Study Center Steven Warren University of Kansas Hary Wright University of S.Carolina School of Medicine Marshalyn Yeargin-Allsopp National Center on Birth Defects and Developmental Disabilities

Nurit Yirmiya The Hebrew University of Jerusalem Paul Yoder Vanderbilt University

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Program Agenda

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8:00am Registration Check-In and Coffee Foyer 8:00-11:00am Brain Symposium Regency ABC A. Brain Volume Chair Diane Chugani Speakers Eric Courchesne Steve Dager

“ Longitudinal Brain Developmental Changes in Young Children with Autism”

Joseph Pi ven

“Longitudinal MRI Study of 18-35 Month Olds with Autism“

B. Brain Development Chair & Speaker Pat Levitt “Interneurons, Development, and Neurodevelopmental Disorders” Speakers Sam Pleasure

“Regulation of Cortical and Diencephalic Development by Wnt Signaling” Kim McAllister

"Rules for the Recruitment of Proteins to New Synapses: a Possible Substrate for Autism?"

8:00-4:00pm Poster Session I Foyer P1.1 Functional Brain Imaging P1.2 Face Processing P1.3 Early Detection, Screening, Diagnosis and Intervention P1.4 Language and Communication P1.5 Psychopharmacology P1.6 Diagnosis and Screening Instruments for Autism Research 11:00-11:15 am Coffee Break Foyer 11:15-12:15pm Keynote Speaker Mark Lewis Regency ABC “Repetitive Behavior in Autism” 12:15-1:15pm Box Lunch 1:15-3:15pm Slide Session I S1.1 Structural and Functional Imaging Regency D Moderator: Blythe Corbett S1.2 Autism and Memory Regency E Moderator: Dermott Bowler

M a y 7, 2 0 0 4

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S1.3 Genetics I Regency F Moderator: Allison Ashley-Koch S1.4 The Gut, Toxins and Nutrients and Autism Golden State AB Moderator: Susan Levy S1.5 Epidemiology Risk Factors & Biomedical Associations Big Sur AB Moderator: Tony Charman S1.6 Special Symposium Autism, Genes and Environment Carmel AB Funded by NIEHS Chairs Isaac Pessah Irva Hertz-Picciotto 3:15-3:30pm Coffee Break Foyer 4:00pm-9:00am Poster Session II Foyer P2.1 Genetics P2.2 Epidemiology P2.3 Structural Brain Imaging P2.4 Intervention P2.5 Perception and Cognition in Early Development 3:30-5:30pm Slide Session II S2.1 Face Processing I Regency D Moderator: Richard Davidson S2.2 Language Processing Regency E Moderator: Shiri Pearlman-Avnion S2.3 Genetics II Regency F Moderator: Allison Ashley-Koch S2.4 Early Intervention Golden State AB Moderator: Jennifer Kuhn S2.5 Early Indicators in Autism Spectrum Disorder Big Sur AB Moderator: Ami Klin S2.6 Special Symposium Autism, Genes and Environment Carmel AB Funded by NIEHS Chairs Issac Pessah Irva Hertz-Picciotto 5:30-6:30pm Reception with Hors D’oeuvres Foyer 6:30-6:45pm 2004 IMFAR Dissertation Award Presentation Regency ABC - Thayne Sweeten 6:45-7:30pm Lifetime Achievement Award Presentation Regency ABC - Marie Bristol-Powers

M a y 7, 2 0 0 4

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8:00am Registration Check-in and Coffee Foyer 8:00-10:00am Slide Session III S3.1 Face Processing II Regency D Moderator: Sara Webb S3.2 Neuropsychological Processes Regency E Moderator: Katherine Loveland S3.3 Genetics III Regency F Moderator: Hill Goldsmith S3.4 School Age Intervention Golden State AB Moderator: Steven Gutstein S3.5 Biological Aspects in Early Development Big Sur AB Moderator: John Lewis S3.6 Development of Young Siblings Carmel AB of Children with Autism Moderator: Nurit Yirmiya 9:00am-5:00pm Poster Session III Foyer P3.1 Biological Markers in Early Development P3.2 Joint Attention, Play and Social Development P3.3 Microbiology and Immunology of Autism Spectrum Disorder P3.4 Perception, Attention, Learning and Memory P3.5 Neuropathology and Basic Studies P3.6 Descriptive and Diagnostic P3.7 Families 10:00-10:15am Coffee Break Foyer 10:15-12:15pm Slide Session IV S4.1 Theory of Mind Regency D Moderator: Peter Hobson S4.2 Cognitive Processes Regency E Moderator: Laurent Mottorn S4.3 Genetics IV Regency F Moderator: Sarika Peters S4.4 Descriptive Diagnostic Golden State AB Moderator: Ina Van Berckelaer-Onnes S4.5 Microbiology and Immunology of Autism Disorder Big Sur AB Moderator: Paul Ashwood 12:15-1:15pm International Society for Autism Research Presidential Address 2004 - Marian Sigman, Ph.D., University of California, Los Angeles

M a y 8, 2 0 0 4

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Program Agenda

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1:15-3:35pm Current Research and Hypotheses About the Regency ABC

Face Processing Abilities of Individuals with Autis m Chair & Speaker Mark Strauss

“Facial Expertise: The Perception and Recognition of Faces by Infants, Preschoolers, and Adults with Autism”

Speakers Nouchine Hadjikhani “Beyond the FFA - Perspectives on Face Perception Deficits in Autism”

Robert Joseph “Are Gaze Processing Deficits Central to the Face Processing Deficits in Autism?” Robert Schultz

"Task Design & Patient Characteristics that Influence Degree of FFA Activation to Faces"

Jane Webb “Two Faced: Dual Theories of Face Processing Deficits in Autism” 3:35-4:00pm Coffee Break Foyer 4:00-5:00pm Keynote Speaker Marcel Just Regency ABC

“Cortical Underconnectivity in High-Functioning Autism: Brain Activation and Brain Synchronization in Cognitive Tasks”

5:30-6:30pm IMFAR Business Meeting Regency AB

M a y 8, 2 0 0 4

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Thematic Guide

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Title Type Session Day Time Room Autism and Memory Slide S1.2 Friday 1:15pm-3:15pm Regency E Autism, Genes and Environment

Slide S1.6 Friday 1:15pm-3:15pm Carmel AB

Autism, Genes and Environment

Slide S2.6 Friday 3:30pm-5:30pm Carmel AB

Biological Aspects in Early Development

Slide S3.5 Saturday 8:00-10:00am Big Sur AB

Biological Markers in Early Development

Poster P3.1 Saturday 9:00am-5:00pm Foyer

Cognitive Processes Slide S4.2 Saturday 10:15am-12:15pm

Regency E

Descriptive and Diagnostic Poster P3.6 Saturday 9:00am-5:00pm Foyer

Descriptive Diagnostic Slide S4.4 Saturday 10:15am-12:15pm

Golden State AB

Diagnosis and Screening Instruments for Autism Research

Poster P1.6 Friday 8:00am-4:00pm Foyer

Early Detection, Screening, Diagnosis and Intervention

Poster P1.3 Friday 8:00am-4:00pm Foyer

Early Indicators in Autism Spectrum Disorder

Slide S2.5 Friday 3:30pm-5:30pm Big Sur AB

Early Intervention Slide S2.4 Friday 3:30pm-5:30pm Golden State AB

Epidemiology Poster P2.2 Friday 4:00pm-9:00am Foyer Epidemiology Risk Factors & Biomedical Associations Slide S1.5 Friday 1:15pm-3:15pm Big Sur AB

Face Processing Poster P1.2 Friday 8:00am-4:00pm Foyer Face Processing I Slide S2.1 Friday 3:30pm-5:30pm Regency D Face Processing II Slide S3.1 Saturday 8:00-10:00am Regency D Families Poster P3.7 Saturday 9:00am-5:00pm Foyer Functional Brain Imaging Poster P1.1 Friday 8:00am-4:00pm Foyer Genetics Poster P2.1 Friday 4:00pm-9:00am Foyer Genetics I Slide S1.3 Friday 1:15pm-3:15pm Regency F Genetics II Slide S2.3 Friday 3:30pm-5:30pm Regency F Genetics III Slide S3.3 Saturday 8:00-10:00am Regency F

Genetics IV Slide S4.3 Saturday 10:15am-12:15pm

Regency F

Intervention Poster P2.4 Friday 4:00pm-9:00am Foyer Joint Attention, Play and Poster P3.2 Saturday 9:00am-5:00pm Foyer

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Thematic Guide

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Social Development Language and Communication

Poster P1.4 Friday 8:00am-4:00pm Foyer

Language Processing Slide S2.2 Friday 3:30pm-5:30pm Regency E Microbiology and Immunology of Autism Disorder

Slide S4.5 Saturday 10:15am-12:15pm Big Sur AB

Microbiology and Immunology of Autism Spectrum Disorder

Poster P3.3 Saturday 9:00am-5:00pm Foyer

Neuropathology and Basic Studies

Poster P3.5 Saturday 9:00am-5:00pm Foyer

Neuropsychological Processes

Slide S3.2 Saturday 8:00-10:00am Regency E

Perception, Attention, Learning and Memory

Poster P3.4 Saturday 9:00am-5:00pm Foyer

Perception and Cognition in Early Development

Poster P2.5 Friday 4:00pm-9:00am Foyer

Psychopharmacology Poster P1.5 Friday 8:00am-4:00pm Foyer

School Age Intervention Slide S3.4 Saturday 8:00-10:00am Golden State AB

Structural and Functional Imaging

Slide S1.1 Friday 1:15pm-3:15pm Regency D

Structural Brain Imaging Poster P2.3 Friday 4:00pm-9:00am Foyer The Gut, Toxins and Nutrients and Autism

Slide S.14 Friday 1:15pm-3:15pm Golden State AB

Theory of Mind Slide S4.1 Saturday 10:15am-12:15pm

Regency D

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Chronological Guide

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Title Type Session Day Time Room Functional Brain Imaging Poster P1.1 Friday 8:00am-4:00pm Foyer Face Processing Poster P1.2 Friday 8:00am-4:00pm Foyer Early Detection, Screening, Diagnosis and Intervention

Poster P1.3 Friday 8:00am-4:00pm Foyer

Language and Communication

Poster P1.4 Friday 8:00am-4:00pm Foyer

Psychopharmacology Poster P1.5 Friday 8:00am-4:00pm Foyer Diagnosis and Screening Instruments for Autism Research

Poster P1.6 Friday 8:00am-4:00pm Foyer

Structural and Functional Imaging

Slide S1.1 Friday 1:15pm-3:15pm Regency D

Autism and Memory Slide S1.2 Friday 1:15pm-3:15pm Regency E Genetics I Slide S1.3 Friday 1:15pm-3:15pm Regency F The Gut, Toxins and Nutrients and Autism

Slide S.14 Friday 1:15pm-3:15pm Golden State AB

Epidemiology Risk Factors & Biomedical Associations

Slide S1.5 Friday 1:15pm-3:15pm Big Sur AB

Autism, Genes and Environment

Slide S1.6 Friday 1:15pm-3:15pm Carmel AB

Genetics Poster P2.1 Friday 4:00pm-9:00am Foyer Epidemiology Poster P2.2 Friday 4:00pm-9:00am Foyer Structural Brain Imaging Poster P2.3 Friday 4:00pm-9:00am Foyer Intervention Poster P2.4 Friday 4:00pm-9:00am Foyer Perception and Cognition in Early Development

Poster P2.5 Friday 4:00pm-9:00am Foyer

Face Processing I Slide S2.1 Friday 3:30pm-5:30pm Regency D Language Processing Slide S2.2 Friday 3:30pm-5:30pm Regency E Genetics II Slide S2.3 Friday 3:30pm-5:30pm Regency F

Early Intervention Slide S2.4 Friday 3:30pm-5:30pm Golden State AB

Early Indicators in Autism Spectrum Disorder

Slide S2.5 Friday 3:30pm-5:30pm Big Sur AB

Autism, Genes and Environment

Slide S2.6 Friday 3:30pm-5:30pm Carmel AB

Face Processing II Slide S3.1 Saturday 8:00-10:00am Regency D Neuropsychological Processes

Slide S3.2 Saturday 8:00-10:00am Regency E

Genetics III Slide S3.3 Saturday 8:00-10:00am Regency F

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Chronological Guide

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School Age Intervention Slide S3.4 Saturday 8:00-10:00am Golden State AB

Biological Aspects in Early Development

Slide S3.5 Saturday 8:00-10:00am Big Sur AB

Biological Markers in Early Development

Poster P3.1 Saturday 9:00am-5:00pm Foyer

Joint Attention, Play and Social Development

Poster P3.2 Saturday 9:00am-5:00pm Foyer

Microbiology and Immunology of Autism Spectrum Disorder

Poster P3.3 Saturday 9:00am-5:00pm Foyer

Perception, Attention, Learning and Memory

Poster P3.4 Saturday 9:00am-5:00pm Foyer

Neuropathology and Basic Studies

Poster P3.5 Saturday 9:00am-5:00pm Foyer

Descriptive and Diagnostic Poster P3.6 Saturday 9:00am-5:00pm Foyer Families Poster P3.7 Saturday 9:00am-5:00pm Foyer

Theory of Mind Slide S4.1 Saturday 10:15am-12:15pm

Regency D

Cognitive Processes Slide S4.2 Saturday 10:15am-12:15pm

Regency E

Genetics IV Slide S4.3 Saturday 10:15am-12:15pm

Regency F

Descriptive Diagnostic Slide S4.4 Saturday 10:15am-12:15pm

Golden State AB

Microbiology and Immunology of Autism Disorder

Slide S4.5 Saturday 10:15am-12:15pm Big Sur AB

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Session Listings

13

M a y 7, 2 0 0 4

Poster Session 1: Topic 1: Functional Brain

Imaging P1.1.1 EEG ASYMMETRY AND SUBTYPES IN AUTISM. P.C. Mundy*, C. Burnette and S.K. Sutton. Department of Psychology, University of Miami, Coral Gables, FL, 33146 P1.1.2 DIFFERENCES IN BRAIN ACTIVATION IN CHILDREN WITH AUTISM INDEPENDENT OF BEHAVIORAL PERFORMANCE. S.M. Rivera*, B. Mikaelian and M.L. Henry. U.C. Davis Dept. of Pschology, Davis, CA 95616 P1.1.3 DIGIT SPAN IN ADULTS WITH ASPERGER'S SYNDROME. M. Poirier, S.B. Gaigg and D.M. Bowler. Department of Psychology, City University, London EC1V 0HB, UK P1.1.4 COGNITION, EMOTION, AND THE RESTING STATE: AN fMRI STUDY OF NEUROFUNCTIONAL ABNORMALITIES IN AUTISM. D.P. Kennedy, E. Redcay and E. Courchesne. Department of Neurosciences, UCSD, Department of Psychology, UCSD, Center for Autism Research, Children's Hospital, San Diego, La Jolla, CA 92037. P1.1.5 A SPECIFIC DEFICIT OF GESTURAL IMITATION IN AUTISTIC SPECTRUM DISORDER. O. Perra, J.H.G. Williams* and A. Whiten. Child Health Dept., Univ. of Aberdeen, Aberdeen, UK, AB25 2ZD; School of Psychology, Univ. of St. Andrews, St. Andrews, UK, KY16 9JP. P1.1.6 UNIQUE BRAIN ACTIVATIONS TO INTEGRATION OF AUDIO-VISUAL EMOTIONAL CUES. D.L. Robins*, E.T. Hunyadi and R.T. Schultz. Yale University Child Study Center, New Haven, CT 06520

P1.1.7 AUDITORY CHANGE DETECTION IN AUTISM: AN fMRI STUDY. M. Gomot, M. Belmonte, C. Ashwin and S. Baron-Cohen. Autism Research Centre, University of Cambridge, Department of Psychiatry, Douglas House, 18b Trumpington Road Cambridge CB2 2AH, UK. P1.1.8 ATYPICAL LATERALITY PATTERNS ASSOCIATED WITH EFFICIENCY OF VISUOMOTOR LEARNING IN AUTISTIC ADULTS. C. Cauich and R-A. Müller*. Dept. of Psychology, San Diego State University; Dept. of Cognitive Science, University of California; San Diego, CA 92120. P1.1.9 BOLD SIGNAL COVARIANCE SUGGESTS MOSTLY INTACT THALAMOCORTICAL FUNCTIONAL CONNECTIVITY IN AUTISM. A. Mizuno, B.C. Dahl, M.E. Villalobos and R-A. Müller *. Brain Development Imaging Lab, San Diego State University, San Diego, CA 92120. P1.1.10 BRAIN SEROTONERGIC ABNORMALITIES IN AUTISTIC CHILDREN. S. Chandana, M. Behen, R. Rothermel, C. Juhasz, O. Muzik, H.T. Chugani and D.C. Chugani. Wayne State Univ., Children’s Hosp. of Mich., Detroit, MI 48201 P1.1.11 ABNORMAL PROCESSING OF HIGH AND LOW SPATIAL FREQUENCIES IN AUTISTIC CHILDREN. M.A. Boeschoten, C. Kemner, J.L. Kenemans and H. van Engeland. Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, 3508 GA, The Netherlands. The Netherlands Organisation for Scientific Research*. P1.1.12 FEAR POTENTIATED STARTLE AND AUTISM. R. Bernier, G. Dawson* and H. Panagiotidas. University of Washington, Box 357920, Seattle WA, 98195.

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Session Listings

14

M a y 7, 2 0 0 4

P1.1.13 WHITE AND GRAY MATTER DIFFERENCES IN AUTISM USING VOXEL-BASED MORPHOMETRY. E.D. Bigler, S.L. Provencal, W. McMahon and J.E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. Poster Session I: Topic 2: Face Processing P1.2.1 BRAIN FUNCTION AND GAZE AVERSION IN INDIVIDUALS WITH AUTISM: EFFECTS OF FAMILIARITY. K.M. Dalton, B.M. Nacewicz, A.L. Alexander, M.A. Gernsbacher, H.H. Goldsmith and R.J. Davidson. Waisman Center, Keck Lab, Univ. of Wisconsin, Madison, WI. 53706. P1.2.2 REDUCED AFFECTIVE SALIENCE OF SOCIAL STIMULI IN AUTISM. J.L. Wilbarger, D.N. McIntosh* and P. Winkielman. Emotion and Cognition Lab, Department of Psychology, University of Denver, Denver, CO 80208. P1.2.3 AUTISM SEVERITY CORRELATED WITH REDUCED BRAIN ACTIVATION DURING A FACE PROCESSING TASK. J.N. Lee, E.D. Bigler, S.L. Provencal, W. McMahon and J. E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. P1.2.4 GAZE AT EYES AND ADI-R. C.Y. Trepagnier*, M.M. Sebrechts, R. Ramloll, M. Coleman, A. Finkelmeyer, L. Barker, M. Paxton Jones, W. Stewart and K. Gleeson. Psychology Department, The Catholic University of America, Washington, DC 20064

P1.2.5 EXPERTISE IN THE ATTRIBUTION OF EMOTION FROM DYNAMIC FACES IN HIGH FUCTIONING INDIVIDUALS WITH SOCIAL UNDERSTANDING DIFFICULTIES. J. Piggot, A. Reiss and J. Hallmayer. Department of Psychiatry and Behavioral Sciences, University of Stanford, CA 94305. P1.2.6 FACE RECOGNITION STRATEGIES USED BY INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS. L. Kopelioff*, V.E. Stone and C.L. Reed. U of Denver and U of Queensland, Dept. of Psychology,U of Denver,Denver,CO,80208 P1.2.7 A STUDY OF PERCEPTIVE HIERARCHIZATION OF FACES IN AUTISM. A. Lahaie, L. Mottron*, M. Arguin, C. Berthiaume, B. Jemel and D. Saumier. Perv. Dev. Disord.Spec. Clin., Riviere-des-Prairies hosp., Montreal, Qc, Can., H1E 1A4. P1.2.8 FAMILIAR FACE RECOGNITION IN CHILDREN WITH AUTISM. R. Wilson*, O. Pascalis and M. Blades. Department of Psychology, University of Sheffield, Sheffield, Yorkshire, S10 2TP, U.K. P1.2.9 AMYGDALA VOLUME AND FUNCTION DURING RECOGNITION OF EMOTIONAL FACIAL EXPRESSIONS. B.M. Nacewicz,* K.M. Dalton, A. Alexander, M. Gernsbacher, H. Goldsmith and R.J. Davidson. Waisman Center, Univ. of Wisconsin, Madison, WI. 53706. P1.2.10 NEURAL MECHANISMS INVOLVED IN LEARNING FROM FACIAL EXPRESSIONS. C.I. Hooker, L.T. Germine, E. Owen, R.T. Knight and M. D’Esposito. Helen Wills Neuroscience Institute & Psychology Department, University of California, Berkeley

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Session Listings

15

M a y 7, 2 0 0 4

Poster session 1: Topic 3: Early Detection,

Screening, Diagnosis and Intervention

P1.3.1 DEVELOPMENT OF VERBAL OPERANTS DURING PIVOTAL RESPONSE TRAINING. D. Rausch-Harris, S. Dufek and L. Schreibman*. University Of California, San Diego 92093-0109 P1.3.2 PREDICTION TO ONE YEAR FOLLOW-UP FROM TARGETED JOINT ATTENTION AND PLAY INTERVENTIONS. C. Kasari, S.F. Freeman and T. Paparella. University of California, Los Angeles*, LA, California, 90024. P1.3.3 DIFFERENTIATING BETWEEN AUTISM SPECTRUM DISORDERS AND OTHER DEVELOPMENTAL DISABILITIES USING THE MODIFIED CHECKLIST FOR AUTISM IN TODDLERS (M-CHAT). P. Dixon, J. Kleinman, J. Pandey, L. Wilson, H. Boorstein, E. Esser, S. Lanz, M. Barton, S. Allen, J. Green, T. Dumont-Mathieu, G. Marshia, D. Robins and D. Fein*. University of Connecticut Psychology Department, Storrs, CT 06269 P1.3.4 SCREENING FOR AUTISM IN PEDIATRIC PRIMARY CARE: RESULTS OF A PILOT STUDY. J.A. Pinto-Martin*, M. Souders, S. Wightman-Hertz, E. Giarelli, S. Levy and PA-CADDRE. Univ.of Penn., Phila., PA 19104 P1.3.5 DEVELOPMENT OF AUTISTIC TRAITS IN YOUNG INFANTS (0-4 YEARS OF AGE) WITH AUTISM AND OTHER SOCIAL DEVELOPMENTAL DISORDERS. F. Naber, S.H.N. Willemsen-Swinkels, E. van Daalen, J.K. Buitelaar, H. van Engeland. Department of Child and Adolescent Psychiatry, University Medical Center Utrecht-The Netherlands, P.O. Box 85500 3508 GA Utrecht.

P1.3.6 EARLY REGRESSION IN SOCIAL COMMUNICATION IN AUTISTIC SPECTRUM DISORDERS. R. Luyster, J. Richler, S. Risi, W. Hsu, C. Lord* and Collaborative Programs for Excellence in Autism (CPEA). University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109. P1.3.7 A POPULATION BASED STUDY ON EARLY DETECTION OF AUTISM SPECTRUM DISORDERS. S. Schjolberg. University of Oslo, Institute of Psychology, Oslo, Norway. Poster Session 1: Topic 4: Language and

Communication P1.4.1 SPONTANEOUS VOCALIZATIONS IN TWO NON-VERBAL CHILDREN WITH AUTISM. M. Boner and B. Gordon. Cognitive Neurology/ Neuropsychology, Johns Hopkins Medical Institutions, Baltimore, MD 21231. P1.4.2 PRAGMATIC RATING SCALES AND ASPERGER SYNDROME: TOWARDS A MATHMATICAL MODEL. J. Harpur, M. Lawlor, K. Ashton and M. Deunk. Health Research Board.* Computer Science, NUIM, Maynooth, Ireland. Child and Family Centre, Drogheda. Trinity College. Department of Psychiatry, Dublin. P1.4.3 IDENTIFYING INDICATORS FOR AUTISM RISK: DEVELOPMENTAL TRAJECTORIES IN JOINT ATTENTION. A. Mastergeorge, M. Lombardo, E. Amini and M. Awad. Early Development and Interaction Laboratory, M.I.N.D. Institute, UC Davis, UCDMC, Sacramento, California 95817 P1.4.4 TRAINING ORAL SPEECH IN NON-VERBAL AUTISM: A CASE STUDY. J. O’Grady, J. Juska, O. Pullara, L. Bejoian and B. Gordon. Johns Hopkins Medical Institutions, Baltimore, MD 21287.

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Session Listings

16

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P1.4.5 VOWELS AND CONSONANTS ARE PROCESSED DIFFERENTLY IN CHILDREN WITH AUTISM: AN ERP STUDY. E.W. Pang*, M.D. Bomba, W.J. Logan and W. Roberts. Division of Neurology, Hospital for Sick Children, Toronto, Canada, M5G 1X8. P1.4.6 TEXT CHAT AS A TOOL FOR REFERENTIAL QUESTIONING IN ASPERGER SYNDROME. G. Rajendran* and P. Mitchell. Sch. of Psy., Univ. of Notts. UK. P1.4.7 SOCIAL AND COMMUNICATION ABILITIES AND DISABILITIES IN HIGHER FUNCTIONING AUTISM, ASPERGER SYNDROME, AND PDD-NOS: THE VINELAND AND THE ADOS. C.A. Saulnier, A. Klin, S.S. Sparrow, D.V. Cicchetti and F.R. Volkmar. Yale Child Study Center, Yale University School of Medicine, New Haven, CT 06520. P1.4.8 A CPEA STUDY OF LANGUAGE HISTORY AND LANGUAGE OUTCOMES IN AUTISM SPECTRUM DISORDERS. H. Tager-Flusberg*, L. McGrath, E.H. Cook, G. Dawson, M. Dunn, S. Hyman, C. Lord, P. Rodier, W. McMahon, N. Minshew, M. Sigman, A. Spence, D. Williams and F.R. Volkmar. *Lab of Developmental Cognitive Neuroscience, Boston University School of Medicine., Boston, MA, 02118-2526. P1.4.9 EARLY PREDICTORS OF LANGUAGE GROWTH IN YOUNG CHILDREN WITH AUTISM: JOINT ATTENTION, IMITATION, AND TOY PLAY. K. Toth, G. Dawson*, A. Meltzoff and J. Munson. University of Washington, Seattle, WA 98195. P1.4.10 MAKING SENSE OF A CONVERSATION: NEURAL CORRELATES OF SYNTAX, SEMANTICS, AND DISCOURSE MONITORING IN CHILDREN WITH AUTISM. A.T. Wang, M. Dapretto, R. Caplan and M. Sigman. UCLA, Los Angeles, CA 90024

P1.4.11 VARIABLE PRESENTATION OF COMPLEX LANGUAGE SKILLS IN HIGH-FUNCTIONING CHILDREN AND ADOLESCENTS WITH AUTISM. D.L. Williams and N. Minshew. University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. P1.4.12 CONVERSATIONAL BREAKDOWN AND REPAIR IN SPEAKERS WITH AUTISM SPECTRUM DISORDER. J. Volden*, Speech Pathology and Audiology, University of Alberta, Edmonton, Alberta, Canada, T6G 2G4. Poster Session 1: Topic 5: Psychopharmacology P1.5.1 EFFICACY AND TOLERABILITY OF METHYLPHENIDATE IN CHILDREN WITH PERVASIVE DEVELOPMENTAL DISORDERS. A. Di Martino and A. Zuddas. Child Psychiatry, Dept of Neuroscience, Cagliari University, Cagliari, Italy P1.5.2 PHARMACOLOGICAL MODULATION OF EMOTION MEMORY IN AUTISM SPECTRUM DISORDERS. A. Hillier, J.S. Chu, R.F. Miller, J. Kitzmiller and D.Q. Beversdorf. The Ohio State University, Columbus, OH 43210. P1.5.3 AN OPEN TRIAL OF GALANTAMINE IN CHILDREN AND ADOLESCENTS WITH AUTISM. R. Nicolson and J. Smith. The University of Western Ontario, London, Ontario, Canada. P1.5.4 SERUM FERRITIN AND RESPONSE TO IRON SUPPLEMENTATION IN AUTISM. W. Roberts*, C. Dosman, I. Drmic, M. Harford, W. Sharieff, R. Smith, H. Moldofsky, S. Zlotkin and J. Brian. Hospital for Sick Children/University of Toronto & Centre for Sleep and Chronobiology Disorders, Toronto, ON, Canada.

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P1.5.5 PSYCHOTROPIC MEDICATION AND BEHAVIORAL THERAPY USE IN CHILDREN WITH AUTISM. K.C. Thomas, J.P. Morrissey* and A. Brewster. Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3386. P1.5.6 ADHD SYMPTOMATOLOGY IN AUTISM: PATTERNS OF PSYCHIATRIC COMORBIDITY AND PSYCHOTROPIC MEDICATION USE. D.A. Pearson and K.A. Loveland. Dept. of Psychiatry, Univ. of TX Med. Sch., Houston, TX 77030. Poster Session 1: Topic 6: Diagnosis and

Screening Instruments for Autism Research

P1.6.1 ANOTHER LOOK AT THE SOCIAL COMMUNICATION QUESTIONNAIRE AND ITS RELATIONSHIP TO THE AUTISM DIAGNOSTIC INTERVIEW. C. Corsello, D. Anderson, S. Qiu, S. Risi and C. Lord*. The University of Michigan Autism and Communication Disorders Center, Ann Arbor, Michigan, 48109. P1.6.2 REPETITIVE BEHAVIORS IN AUTISM SPECTURM DISORDERS: RELATIONSHIPS WITH ASSOCIATED CLINICAL FEATURES. R.L. Gabriels*, M. Cuccaro, L.G. Ogden, D.E. Hill and B. Ivers. University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 P1.6.3 PARENT REPORT OF SYMPTOMATOLOGY IN AUTISM SPECTRUM DISORDERS: CHANGE BETWEEN INITIAL AND FOLLOW-UP EVALUATIONS. L. Gilotty, P. Lee, G. Wallace, M.C. Gibbs, D. Black and L. Kenworthy*. Center for Autism Spectrum Disorders, Children’s National Medical Center, Washington, DC 20010.

P1.6.4 DIAGNOSTIC STABILITY OVER A 2-YEAR TIME PERIOD IN PRESCHOOLERS WITH AUTISM SPECTRUM DISORDERS. J. Kleinman, J. Pandey, P. Dixon, L. Wilson, H. Boorstein, E. Esser, M. Barton, S. Allen, J. Green, G. Marshia, D. Robins and D. Fein*. University of Connecticut Psychology Department, Storrs, CT 06269; P1.6.5 LIPIDOMICS IN AUTISM: ALTERATIONS IN WHITE MATTER PHOSPHOLIPIDS. O. Koul, B. Evans and J. Evans. Department of Biochemistry and Molecular Pharmacology, and Shriver Center, 200 Trapelo Road, Waltham, MA 02452 P1.6.6 FAMILY RESOURCES PREDICT AGE AT DIAGNOSIS BEYOND THE COHORT EFFECT. A.S. Carter* and J.C. Kuhn*. Department of Psychology, University of Massachusetts Boston, Boston, MA 02125. P1.6.7 DEVELOPMENT OF THE COMFOR. I.L.J. Noens and I.A. Van Berckelaer-Onnes. Leiden University, The Netherlands. P1.6.8 THE MODIFIED CHECKLIST FOR AUTISM IN TODDLERS: AN UPDATE. J. Pandey, J. Kleinman, P. Dixon, L. Wilson, H. Boorstein, E. Esser, S. Lanz, M. Barton, S. Allen, T. Dumont-Mathieu, J. Green, G. Marshia, D. Robins and D. Fein*. University of Connecticut Psychology Department, Storrs, CT 06269; Yale University Child Study Center, New Haven, CT 06520. P1.6.9 AUTISM-SCREENING QUESTIONNAIRE DISCRIMINATES BETWEEN CHILDREN WITH AUTISM, NON-SIBLING CONTROLS AND SIBLINGS. S.M. Stephens-Groff, R.C. Bay and R.D. Melmed. Assist. Prof. in Clin. Ped., Univ. of Az, Sch. of Med.; Adjunct Prof., Az. State Univ., respectively. P1.6.10 IDENTIFICATION OF PERVASIVE DEVELOPMENTAL DISORDERS IN CHILDREN AND ADULTS WITH MENTAL RETARDATION. M. Thys and H. Roeyers. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium, B-9000

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P1.6.11 VALIDITY OF THE PDQ-1 AND ABC AS AUTISM SCREENERS. W. Zahorodny, M. Brimacombe, V. Rodriguez, J. Vidal and M. Goldfarb. New Jersey Medical School, Newark, NJ. Slide Session 1: Topic 1: Structural and

Functional Imaging S1.1.1 fMRI OF EVENT-RELATED RESPONSE TO VISUAL DISTRACTORS IN AUTISM. M.K. Belmonte* and S. Baron-Cohen. Autism Research Centre, Departments of Psychiatry and Experimental Psychology, University of Cambridge, CB2 2AH, UK S1.1.2 PROTON SPECTROSCOPY IN DEVELOPMENTALLY DELAYED YOUNG CHILDREN WITH AND WITHOUT AUTISM SPECTRUM DISORDERS. M. Zeegers, J. van der Grond, E. van Daalen, S.H.N. Willemsen-Swinkels, H. van Engeland and J.K. Buitelaar. Department of Child and Adolescent Psychiatry, University Medical Centre Utrecht, The Netherlands. S1.1.3 AN MRI STUDY OF THE ORBITOFRONTAL CORTEX IN AUTISM. A.Y. Hardan*, A. Lacerda, O. Yorbik, M.S. Keshavan and N. Minshew. University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. S1.1.4 NEUROANATOMY IN YOUNG GIRLS WITH AUTISM: A PRELIMINARY STUDY. C.S. Bloss and E. Courchesne.* The Center for Autism Research, University of California, San Diego and Children’s Hospital Research Center. San Diego, CA 92037. S1.1.5 AUTISM SPECTRUM DISORDERS AND MACROCEPHALY. E. van Daalen, S.H.N. Willemsen-Swinkels, J.K. Buitelaar and H. van Engeland. University Medical Center of Utrecht, P.O. box 85500, 3508 GA Utrecht, The Netherlands.

S.1.1.6 CORTISOL DYSREGULATION IN CHILDREN WITH AUTISM . B.A. Corbett,* M. Abdullah, S. Mendoza and S. Levine. UC Davis Department of Psychiatry and Behavioral Sciences. Psychology Department and M.I.N.D. Institute, Sacramento CA, 95817. Slide Session 1: Topic 2: Autism and Memory S1.2.1 POOR SEMANTIC ACTIVATION AND INTERFERENCE IN AUTISM. K. Boser, H. Haarmann and M. Knobel. Johns Hopkins Univ., Baltimore, MD., 21287 Univ. of MD, College Park, MD 20742. S1.2.2 EFFECTS OF RELATED AND UNRELATED CONTEXT ON MEMORY IN ASPERGER'S SYNDROME. D.M. Bowler, J.M. Gardiner and S.B. Gaigg. Department of Psychology, City University, London EC1V 0HB, UK S1.2.3 A PROFILE OF MEMORY FUNCTION IN CHILDREN WITH AUTISM. G. Goldstein, D.L. Williams and N. Minshew. Univ. of Pittsburgh Sch. of Med., Pittsburgh, PA 15213. S1.2.4 A FURTHER CHARACTERIZATION OF COMPLEX COGNITIVE ABILITIES IN HIGH FUNCTIONING AUTISM. N. Minshew, D.L. Williams and G. Goldstein, Univ. of Pittsburgh Sch. of Med., Pittsburgh, PA 15213. S1.2.5 RELATIONAL AND ITEM-SPECIFIC ENCODING IN FREE RECALL IN ASPERGER'S SYNDROME. S.B. Gaigg, D.M. Bowler and J.M. Gardiner. Department of Psychology, City University, London EC1V 0HB, UK

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Slide Session 1: Topic 3: Genetics I S1.3.1 FAMILY HISTORY MAY PLAY A ROLE IN THE ASSOCIATION OF SEROTONIN TRANSPORTER GENE (SLC6A4) POLYMORPHISMS IN AUTISM. R. Rabionet (1), A. Konidari (1), C.M. Wolpert (1), S.L. Donnelly (1), R.K. Abramson (2), H.H. Wright (2), M. Cuccaro (1), J.R. Gilbert (1) and M.A. Pericak-Vance*(1). (1) Dept of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710 (2) WS Hall Psychiatric Institute, University of South Carolina, Columbia, SC 29208 S1.3.2 LINKAGE AND ASSOCIATION OF AN ASPARTATE/GLUTAMATE CARRIER WITH AUTISM: GENETIC VARIANTS ARE ASSOCIATED WITH A SEVERAL-FOLD INCREASED RISK. J.D. Buxbaum*, N. Ramoz, C.J. Smith, J.M. Silverman and I. Bespalova. Lab of Molecular Neuropsychiatry, Department of Psychiatry, Mt Sinai School of Medicine, New York, NY10029 S1.3.3 POSITIVE ASSOCIATION OF THE GENE CNTNAP2 TO AUTISM-RELATED TRAITS. M. Alarcón, R.M. Cantor, J.L. Stone, S.F. Nelson, AGRE Consortium and D.H. Geschwind*. UCLA Human Genetics and Neurology departments, Los Angeles, CA 90095. S1.3.4 GLYOXALASE I AS AN AUTISM SUSCEPTIBILITY GENE. M.A. Junaid*, D. Kowal, M. Barua, P.S. Pullarkat and R.K. Pullarkat. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314.

S1.3.5 NOVEL MUTATIONS OF CANDIDATE GENES IN AUTISM POPULATION. T. Yamagata, M. Mori, K. Suwa, H. Li and M.Y. Momoi*. Department of Pediatrics, Jichi Medical School, Tochigi, 329-0498, Japan S1.3.6 THE PLATELET HYPERSEROTONEMIA OF AUTISM: INVESTIGATING THE PHENOTYPE AND THE GENETIC DETERMINANTS. E.J. Mulder, G.M. Anderson*, J.A. den Boer, I.P. Kema and R. Minderaa. Child & Adolescent Psychiatry Center, PO Box 660, 9700 AR Groningen, the Netherlands. Slide Session 1: Topic 4: The Gut, Toxins, &

Nutrients & Autism S1.4.1 NUTRIENT, TOXIN AND ENZYME PROFILE OF AUTISTIC CHILDREN. T. Audhya. Vitamin Diagnostics Laboratory*, Rt. 35 & Industrial Drive, Cliffwood Beach NJ 07735. W.R. McGinnis, 944 Pinecrest Terrace, Ashland OR 97520. S1.4.2 GASTROINTESTINAL ABNORMALITIES IN CHILDREN WITH AUTISTIC SPECTRUM DISORDER. S. Levy, M. Souders, R. Ittenbach, J. Pinto-Martin and the PA-CADDRE. Children's Hospital of Philadelphia 3405 Civic Center Boulevard Philadelphia, PA 19104 S1.4.3 TREATMENT OF CHILDREN WITH AUTISM WITH LOW DOSE COD LIVER OIL. M.N. Megson, M.D. F.A.A.P. Pediatric and Adolescent Ability Center 7229 Forest Aveune, Suite 211 Richmond, Virginia 23226 S1.4.4 TOXIC AND ESSENTIAL METALS IN BABY HAIR OF CHILDREN WITH AUTISM. J.B. Adams and J. Romdalvik. Arizona State University, Tempe, AZ 85287-6006

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Slide Session 1: Topic 5: Epidemiology Risk

Factors and Biomedical Associations

S1.5.1 MATERNAL AUTOIMMUNE AND ALLERGIC DISEASES AND CHILDHOOD AUTISM. L.A. Croen*, C.K. Yoshida, R. Odouli and J.K. Grether. Kaiser Permanente Division of Research, Oakland, CA, 94612. S1.5.2 HEAD CIRCUMFERENCE IN AUTISM SPECTRUM DISORDERS: A CPEA NETWORK STUDY. J.E. Lainhart, E. Dinh, H. Coon, E.D. Bigler, W. McMahon, The University of Utah, Salt Lake City, UT 84103 and the NICHD CPEA Network. S1.5.3 PERVASIVE DEVELOPMENTAL DISORDERS IN CANADA - POPULATION COMPARISON ACROSS TWO CANADIAN PROVINCES. H. Ouellette-Kuntz*, H. Coo, C.T. Yu, A.E. Chudley, A. Noonan, M. Breitenbach, N. Ramji, T. Prosick, A. Bedard and J.J.A. Holden. The ASD-CARC Epidemiology Project Team. *Department of Community Health and Epidemiology, Queen’s University, Kingston, Ontario, Canada, K7M 8A6 S1.5.4 THE CO-OCCURRENCE OF AUTISM AND BIRTH DEFECTS. D. Schendel, R. Wines, C. Moore and T. Karapurkar. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-86, Atlanta, GA 30333. S1.5.5 AGE AT FIRST MMR VACCINATION AMONG CHILDREN WITH AUTISM AND SCHOOL-MATCHED CONTROLS IN METROPOLITAN ATLANTA. W. Thompson*, T. Karapurkar, F. DeStefano, M. Yeargin-Allsopp and C. Boyle. CDC, Atlanta, GA 30333.

Slide Session 1: Topic 6: Special Symposium: Autism, Genes, and Environment Funded by NIEHS Chair: Isaac Pessah, Ph.D., Dept. of Molecular Biological Sciences, University of California, Davis S1.6.1 CHILDREN’S ENVIRONMENTAL HEALTH: ISSUES AND CHALLENGES. E.K. Silbergeld. Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore MD 21205. S1.6.2 EXPOSURES TO METALS AND NEURODEVELOPMENTAL DISORDERS IN CHILDREN. D.C. Bellinger. Harvard Medical School Children’s Hospital Boston S1.6.3 EPIDEMIOLOGIC EVALUATION OF GENE-ENVIRONMENT INTERACTION IN CAUSATION OF AUTISM. J.K. Grether. California Center for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) S1.6.4 IMPACT OF ENVIRONMENTAL CHEMICALS ON NEUROPSYCHOLOGICAL DEVELOPMENT OF CHILDREN: WHAT CAN WE LEARN FROM ANIMAL MODELS? S.L. Schantz. Department of Veterinary Biosciences and Neuroscience Program, University of Illinois at Urbana-Champaign. Poster Session 2: Topic 1: Genetics P2.1.1 THE ROLE OF MeCP2 IN GENE EXPRESSION REGULATION DURING NEURONAL DIFFERENTIATION. S. Peddada and J.M. LaSalle*. Med Micro& Immuno, UC Davis Sch.of Med., Davis, CA 95616

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P2.1.2 INSISTENCE ON SAMENESS AND BLOOD SEROTONIN IN INDIVIDUALS WITH AUTISTIC DISORDER . R.K. Abramson, A.V. Hall, S.A. Ravan, M. Cuccaro, E.H. Cook and H.H. Wright.* Dept Neuropsychiatry, Univ S Carolina Sch Med, Columbia, SC 29203. P2.1.3 DBH POLYMORPHISMS AND SERUM ACTIVITY IN AN FAMILY BASED IRISH POPULATION SUFFERING AUTISM. J. Conroy, N. Murphy, E. Meally , G. Kearney, M. Fitzgearld, G. Anderson, M. Gill and L. Gallagher. Smurfit Institute, Dept.s of Genetics and Psychiatry, Trinity College Dublin, Ireland and Child Study Center, New Haven, CT 06516, USA. P2.1.4 MUTATION SCREENING AND EXPRESSION ANALYSIS OF A CANDIDATE GENE FOR AUTISM. J.A. Duvall 1, J. Simon 4, K. Wilkes 2, J.L. Stone 1, S.F. Nelson 1, E.H. Cook 3, D.H. Ledbetter 3,5, C.L. Martin 3 and D.H. Geschwind 2*. 1)Depts. of Human Genetics, and 2)Neurology, UCLA Sch. of Med., LA, CA 90095; 3)Dept. of Human Genetics, Univ. of Chicago, Chicago, IL 60637; 4)Schering-Plough Research Inst., Kenilworth, NJ 07033; 5)Dept. of Human Genetics, Emory Univ., Atlanta, GA 30322 . P2.1.5 CHROMOSOME X-WIDE ASSOCIATION STUDY IN AUTISM. J. Gauthier, R. Joober, J. St-Onge, A. Bonnel, D. Gariépy, H. Lacasse, D. Verlaan, R. Najafee, É. Fombonne, L. Mottron and G.A. Rouleau.Research Institute of the McGill University Health Center, 1650 Cedar Ave, Montreal, H3G1A4, Canada P2.1.6 BIOMARKER DISCOVERY THROUGH GENOMIC-ARRAY PROFILING OF AUTISM. J. Gregg*, W. Zhang, C. Baron and D. Milliken. M.I.N.D. Institute, Departments of Pathology.

P2.1.7 DETAILED PHENOTYPING AND GENOTYPING OF MULTIPLEX AND SIMPLEX FAMILIES WITH AUTISM SPECTRUM DISORDERS. J.J.A. Holden* and the Autism Spectrum Disorders Canadian-American Research Consortium. Dept. Psychiatry & Physiology, Queens University, Kingston, Ontario. P2.1.8 EXAMINATION OF PARENT OF ORIGIN EFFECTS AT AUTISM SUSCEPTIBILITY LOCI ON CHROMOSOMES 2, 7 AND 15. J. Jaworski, A.E. Ashley-Koch, M. Cuccaro, J.R. Gilbert and M.A. Pericak-Vance*. Duke University Medical Center, Durham, NC 27710. P2.1.9 THE AUTISM GENETIC RESOURCE EXCHANGE: A NOVEL COLLABORATIVE RESOURCE FOR THE STUDY OF AUTISM GENETICS. C.M. Lajonchere*, S.J. Spence, T. Brown, T.C. Gilliam, P. Iversen, C.L. Martin and D. Geschwind. Cure Autism Now, Los Angeles, CA, 90036. P2.1.10 INCREASED INCIDENCE OF MATERNAL HLA-DR4 IN SINGLE-BIRTH, BUT NOT MULTIPLEX FAMILIES WITH AUTISM. L-C. Lee, A. Zachary, S. Leffell, C. Newschaffer, K. Matteson, J. Tyler and A. Zimmerman. Johns Hopkins Univ. Sch of Public Health, Ctr for Autism & Developmental Disabilities Epidemiology, Sch of Med, & Kennedy Krieger Institute, Baltimore, MD 21205; Univ. of Tenn, Knoxville, TN 37920. P2.1.11 ORDERED SUBSETS LINKAGE ANALYSIS ON SAVANT SKILLS OF AUTISTIC DISORDER IN 15Q11-Q13. D. Ma, J. Jaworski, M. Menold, S. Donnelly, R.K. Abramson, H.H. Wright, J.R. Gilbert, M.A. Pericak-Vance* and M. Cuccaro. Duke University Medical Center, Durham NC, 27710 P2.1.12 BUCCAL BRUSHING FOR DNA COLLECTION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. P. Manning-Courtney, C.A. Molloy, A.L. Morrow, G. Radloff and S.M. Davies. Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.

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P2.1.13 INCREASED LIPID PEROXIDATION IN CHILDREN WITH AUTISM. X. Ming*, T.P. Stein, M. Brimacombe, T. Ticinetti, M.L.A. Daniels, W.G. Johnson and G. Lambert. The Autism Center, UMDNJ-New Jersey Medical School, Newark, NJ 07103 P2.1.14 IDENTIFICATION OF POSSIBLE EPISTATIC GENES INVOLVED IN DEVELOPMENT OF AUTISM WITH FRAGILE X SYNDROME. S.T. Nowicki, L. Li, S. Jacquemont, J.P. Gregg, R.J. Hagerman, D.M. Rocke and P.J. Hagerman*. M.I.N.D. Institute, Departments of Pediatrics, Pathology, Biological Chemistry, School of Medicine, and Department of Applied Science, Division of Biostatistics, University of California, Davis, CA, 95616. P2.1.15 BEHAVIOR ANALYSIS OF SECRETIN RECEPTOR DEFICIENT MICE AS MODEL ANIMALS FOR AUTISM. I. Nishijima 1, T. Yamagata 4, C.M. Spencer 2, O. Alekseyenko 2, E. Weeber 3, J.D. Sweatt 3, M.Y. Momoi 4, R. Paylor 2, D.L. Nelson 2and A. Bradley 2. 1Department of Pediatrics, The Ohio State University, Columbus, OH 43205. 2Department of Molecular and Human Genetics, 3Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030. 4Department of Pediatrics, Jichi Medical School, Tochigi, Japan. P2.1.16 MICROARRAY ANALYSES OF LYMPHOID CELLS FOR AUTISM SUSCEPTIBILITY GENES. R.K. Pullarkat*, D. Kowal, P.S. Pullarkat and M.A. Junaid. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 P2.1.17 DEVELOPMENT AND VALIDATION OF A CHROMOSOME 15 DNA MICROARRAY FOR COMPARATIVE GENOMIC HYBRIDIZATION AND APPLICATION TO AUTISM. T. Sahoo, W. Yu, C. Shaw and A. Beaudet. Baylor College of Medicine, Houston, TX.

P2.1.18 EFFECT OF MECP2 MUTATION ON EXPRESSION OF TWO CONDITIONALLY IMPRINTED GENES ON CHROMOSOME 15. R.C. Samaco, T.L. Simcox, A. Hogart, D. Braunschweig and J.M. LaSalle*. Med Micro and Immuno, Rowe Program in Human Genetics, School of Medicine, UC Davis, CA 95616 P2.1.19 MECP2 EXPRESSION CHANGES DURING NEURONAL DIFFERENTIATION. Y.M. Rao and J.M. LaSalle*. Med. Micro. and Immuno., Rowe Pr. in Hum. Genet., UC Davis, CA 95616 P2.1.20 ANALYSIS OF EPIMUTATION IN THE 15q11-13 IMPRINTED DOMAIN IN AUTISM. M. Shinawi, R. Wagle, T. Sahoo, R.J. Schroer, R. Stevenson and A.L. Beaudet. Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas,USA. Greenwood Genetic Center, South Carolina 29646, USA P2.1.21 CHROMOSOME 7 BREAKPOINTS CORRESPOND TO LINKAGE PEAKS AND INDICATE CANDIDATE GENES FOR AUTISM SUSCEPTIBILITY. D.A. Skaar(1), L. Christ(2), M. Cuccaro(1), J.R. Gilbert(1), S. Schwartz(2) and M.A. Pericak-Vance*(1). (1)Center for Human Genetics, Duke University Medical Center, Durham, NC; 2) Dept. of Genetics, Case Western Reserve University, Cleveland, OH P2.1.22 HOMOLOGOUS PAIRING OF 15Q11-13 IMPRINTED DOMAINS IN BRAIN IS DEVELOPMENTALLY REGULATED BUT DEFICIENT IN RETT AND AUTISM SAMPLES. K.N. Thatcher, D. Braunschweig, R.C. Samaco, J.M. LaSalle*. Medical Microbiology & Immunology, UC Davis Sch. Med., Davis, CA 95616.

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P2.1.23 A REVIEW OF CYTOGENETIC ABNORMALITIES IN AUTISM: IMPLICATIONS FOR GENETIC STUDIES. J.A.S. Vorstman, W.G. Staal, E. van Daalen and H. van Engeland. Department of Child and Adolescent Psychiatry Heidelberglaan 100 3584 CX Utrecht, The Netherlands P2.1.24 RH AND ABO MATERNAL-FETAL INCOMPATIBILITY AND RISK OF AUTISM. P.P. Zandi, M.D. Fallin, D. Avramopoulos, Y. Huo and C.J. Newschaffer. Departments of Mental Health and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. P2.1.25 BLOOD SEROTONIN AND YALE BROWN OBSESSIVE COMPULSIVE BEHAVIOR SCALE SCORES IN PARENTS OF PROBANDS WITH AUTISTIC DISORDER. H.H. Wright,* R.K. Abramson, A.V. Hall, S.A. Ravan, E.H. Cook and M. Cuccaro. Dept. Neuropsychiatry, Univ S Carolina Sch Med, Columbia, SC 29203 Poster Session 2: Topic 2: Epidemiology P2.2.1 BIRTH & FAMILY HISTORY RELATED RISK FACTORS IN A COHORT OF AUTISTIC PATIENTS. M. Brimacombe, M. Lamendola, A. Parikh, M.L.A. Daniels and X. Ming*. New Jersey Medical School, Newark NJ 07101-1709. P2.2.2 WISC PROFILES IN CHILDREN WITH AUTISM AND PDD. S. Chandler, T. Loucas, G. Baird, T. Charman and E. Simonoff. A. Pickles. School of Medicine and Biomedical Sciences, King’s College London, SE1 3SS. United Kingdom. Susie.Chandler@kcl.ac.uk P2.2.3 NEW JERSEY ANSWERS FOR AUTISM SURVEY. F. Desposito, W. Zahorodny and M. Brimacombe. New Jersey Medical School, Newark, NJ 07103.

P2.2.4 MERITS AND DEMERITS OF EARLY SCREENING FOR AUTISM SPECTRUM DISORDERS. C. Dietz, S.H.N. Willemsen-Swinkels, E. van Daalen, J.K. Buitelaar and H. van Engeland. UMC-Utrecht, Department of Child and Adolescent Psychiatry, Post box 85500, 3508 GA, Utrecht, The Netherlands. P2.2.5 CHARACTERISTICS OF YOUTH WITH ASPERGER’S DISORDER REFERRED FOR PSYCHIATRIC SERVICES. D. Edgell*, R. Lampard and S.A. Johnson. Queen Alexandra Centre for Children’s Health, Child, Youth & Family Mental Health Services, Vancouver Island Health Authority, Victoria BC, V8N 1V7. P2.2.6 AUTISM PREVALENCE BY BIRTH COHORT FROM US SPECIAL EDUCATION DATA. M.D. Falb, J.G. Gurney* and C.J. Newschaffer. Center for Autism and Developmental Disabilities Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; *Univ. of MN, Minneapolis, MN 55455. P2.2.7 EPIDEMIOLOGY OF AUTISM AMONG CALIFORNIA-BORN TWINS. J.K. Grether*, M. Anderson, B. Hopkins, L.A. Croen, P. Choate and R. Huff. California Department of Health Services, Oakland, CA 94612 P2.2.8 CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT. R.L. Hansen*, I. Hertz-Picciotto, L.A. Croen, M. Sigman, G.G. Hughes, A. Harley, C. Beck and A. French. M.I.N.D. Institute, UCDavis, Sacramento, CA; and UCLA, Los Angeles, CA; P2.2.9 WHY SEARCH FOR ENVIRONMENTAL FACTORS IN AUTISM? I. Hertz-Picciotto, L.A. Croen and R.L. Hansen. M.I.N.D. Institute and Departments of Epidemiology and Preventive Medicine, and of Pediatrics, University of California Davis; Kaiser Permanente Division of Research .

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P2.2.10 MEDICAID EXPENDITURES FOR CHILDREN WITH AUTISM: 1994 THROUGH 1999. R.F. Ittenbach, J. Cao, D.S. Mandell, S.E. Levy, J. Pinto-Martin*. University of Pennsylvania CADDRE, School of Nursing, The University of Pennsylvania, Philadelphia, PA 19104. P2.2.11 CHARACTERISTICS OF CHILDREN WITH AUTISTIC SPECTRUM DISORDERS SERVED IN COMMUNITY MENTAL HEALTH SETTINGS, AND CORRELATES OF PHYSICAL AND SEXUAL ABUSE. D.S. Mandell*, C.M. Walrath, B. Manteuffel, G. Sgro, J.A. Pinto-Martin and PA-CADDRE. University of Pennsylvania School of Medicine, Philadelphia, PA 19104. P2.2.12 INVESTIGATING DEVELOPMENTAL DELAYS STUDY: COMPARISON OF SCQ AND PDDST. C.J. Newschaffer, L-C. Lee, A.B. David and N.L. Lee. Center for Autism and Developmental Disabilities Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. P2.2.13 ENVIRONMENTAL TOXINS AND DEVELOPMENTAL DISORDERS: A U.S. ECOLOGICAL STUDY. R. Palmer*. University of Texas Health Science Center San Antonio, Dept of Family and Community Medicine, San Antonio Texas, 78232 P2.2.14 AUTISM IN CALIFORNIA: EPIDEMIC OR ILLUSION? D. Pyles. Dept. of Education, CSU Dominguez Hills, Carson, CA 90747 P2.2.15 POPULATION-BASED MONITORING OF THE AUTISM SPECTRUM DISORDERS VIA RECORD REVIEW: OPERATIONALIZING THE DSM-IV TR CRITERIA. C. Rice*1, G. McGee 2, M. Morrier 2, C. Lord 3, J Baio 1 and L. Wiggins 1. 1Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-86, Atlanta, GA 30333; 2Emory University; 3University of Michigan.

P2.2.16 ARE CHILDREN WITH AUTISM MORE LIKELY TO REPORT ALLERGIC DISORDERS COMPARED TO HEALTHY CONTROLS? T. Webb*, J. Meinzen-Derr, S. Wilson and M. Wess. University of Cincinnati, Cincinnati, OH 45267 P2.2.17 A COLLABORATIVE NETWORK FOR MONITORING THE AUTISM SPECTRUM DISORDERS IN THE UNITED STATES. J. Wojcik* and ADDM CADDRE Network. CDC, 1600 Clifton Road, MS E-86, Atlanta, GA 30333. P2.2.18 EARLY HEAD GROWTH IN AUTISM. C.K. Yoshida*, L.A. Croen, R. Odouli, M. Wier, R.L. Hansen, J.K. Grether and K.B. Nelson. Kaiser Permanente Division of Research, Oakland, CA, 94612. P2.2.19 NEW JERSEY ANSWERS FOR AUTISM SURVEY. M. Brimacombe, W. Zahorodny and F. Desposito. New Jersey Medical School, Newark, NJ 07103. Poster Session 2: Topic 3: Structural Brain

Imaging P2.3.1 MRI VOLUMETRIC ANALYSES OF THE MEDIAL TEMPORAL LOBE IN AUTISM AND ASPERGER SYNDROME. C.M. Schumann*, J. Hamstra, B.L. Goodlin-Jones, M.H. Buonocore, C.R. Lammers and D.G. Amaral. The M.I.N.D. Institute, UC Davis, Sacramento, CA 95817. P2.3.2 SUPERIOR TEMPORAL GYRUS ABNORMALITIES IN CHILDREN WITH AUTISM. A.Y. Hardan*, M. Vitale, S. Muddasani, M.S. Keshavan and N. Minshew. Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA 15213.

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P2.3.3 BRAIN VOLUMES IN BIOLOGICAL NON-AFFECTED PARENTS OF AUTISTIC PROBANDS. S. Palmen 1, H. Hulshoff Pol 2, C. Kemner 1, H. Schnack 2, R. Kahn 2 and H. van Engeland 1. Departments of Child and Adolescent Psychiatry1 and Psychiatry2, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. P2.3.4 REPETITIVE BEHAVIOR IN AUTISM SPECTRUM DISORDER: THE RELATIONSHIP BETWEEN BRAIN AND BEHAVIOR. K. Dominick, R. Killiany, G.J. Harris and H. Tager-Flusberg*. Lab of Developmental Cognitive Neuroscience, Boston Univ. School of Med., Boston, MA 02118. P2.3.5 BRAIN GROWTH DIFFERENCES IN AUTISM FROM BIRTH TO 46 YEARS: A META-ANALYSIS. E. Redcay* 1 and E. Courchesne 2. Departments of Psychology1, Neurosciences2, UCSD, San Diego, CA 92037. P2.3.6 TRANSVERSE RELAXATION TIME ABNORMALITIES OF FRONTAL-SUBCORTICAL CIRCUITS IN AUTISM. J. Hendry, T. DeVito, N. Gelman, N. Rajakumar, P. Williamson, W. Pavlosky, D.J. Drost and R. Nicolson. University of Western Ontario, London, Ontario, Canada P2.3.7 MRI-BASED PARCELLATION OF THE CEREBELLUM IN AUTISM AND SLI. S.M. Hodge, N. Makris, G.J. Harris*, L. McGrath, S. Steele, D.N. Kennedy, V.S. Caviness Jr., J. Frazier and H. Tager-Flusberg. Mass. General Hospital, Charlestown, MA 02114 and Boston University School of Medicine, Boston, MA 02118. P2.3.8 STRUCTURAL MAGNETIC RESONANCE IMAGING OF THE CEREBELLUM IN AUTISM SPECTRUM DISORDER. J. Hamstra*, C.M. Schumann, B.L. Goodlin-Jones, M.H. Buonocore, C.R. Lammers and D.G. Amaral. The M.I.N.D. Institute UC Davis, Sacramento, CA 95817.

P2.3.9 WHITE AND GRAY MATTER DIFFERENCES IN AUTISM USING VOXEL-BASED MORPHOMETRY. E.D. Bigler, S.L. Provencal, W. McMahon and J.E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. Poster Session 2: Topic 4: Intervention P2.4.1 IMPROVING EMOTION RECOGNITION USING VIDEO MODELING IN A CHILD WITH AUTISM. M. Abdullah and B.A. Corbett*. UC Davis Department of Psychiatry and Behavioral Sciences and M.I.N.D. Institute, Sacramento CA, 95817. P2.4.2 VIDEO DOCUMENTATION OF FUNCTIONAL DEVELOPMENT IN A PRESCHOOLER WITH AUTISM IN RESPONSE TO EARLY INTERVENTION USING THE DIR APPROACH (DEVELOPMENTAL, INDIVIDUAL DIFFERENCE, RELATIONSHIP-BASED APPROACH). C.J. Claflin*. Northwest Missouri State University, Maryville, MO 64468. P2.4.3 A NURSING INTERVENTION FOR PARENTS AFTER A CHILD IS DIAGNOSED WITH AUTISM SPECTRUM DISORDER: RESULTS OF A PILOT STUDY. E. Giarelli, M. Souders, R. Ittenbach, J. Pinto-Martin* and PA-CADDRE. University of Pennsylvania, Philadelphia, PA 19104. P2.4.4 PEER-MEDIATED SOCIAL SKILLS TRAINING FOR CHILDREN WITH HIGH-FUNCTIONING AUTISM. K.M. Chung, S. Reavis, M. Mosconi*, J. Drewry, T. Matthews and M. Tasse. Center for Development and Learning, University of North Carolina - Chapel Hill, Department of Psychology, Chapel Hill, NC 27599.

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P2.4.5 PRACTICE PATTERNS IN COMMUNITY EARLY INTERVENTION PROGRAMS FOR CHILDREN WITH AUTISM: PRELIMINARY FINDINGS FROM THE FIELD. A. Stahmer.* Child and Adolescent Services Research Center, Children’s Hospital, San Diego, CA 92123 P2.4.6 ECOBEHAVIORAL ASSESMENT OF INCLUSIVE PRESCHOOL CLASSES INVOLV ING CHILDREN WITH AUTISM. S.L. Odom, L. Tsao and K. Hume. School of Education, Indiana University, Bloomington, IN 47405-1006 P2.4.7 THE EFFECTS OF PLAY GROUPS ON SYMBOLIC AND SOCIAL PLAY FOR PRESCHOOL CHILDREN WITH AUTISM IN TAIWAN. T.R. Yang*. The Department of Special Education, National Taipei Teachers College, Taipei, Taiwan. 134 Sec. 2 Ho-Ping E. Rd. Taipei 112, Taiwan Poster Session 2: Topic 5: Perception and

Cognition in Early Development

P2.5.1 INFLEXIBLE THINKING OR INFLEXIBLE RESPONDING? ANALYSIS OF ERRORS COMMITTED BY CHILDREN WITH AUTISM ON THE FLEXIBLE ITEM SELECTION TASK. O. Landry, S. Jacques and J.A. Burack*. Dept. of Educ. Psych., McGill Univ., Montreal, QC, Canada H3A 1Y2 P2.5.2 EXECUTIVE FUNCTIONS IN CHILDREN WITH ASPERGER SYNDROME. V.N. Salimpoor and M.E. Desrocher. Autism Society of Ontario*, York University, Toronto, Ontario, M3J-1P3

P2.5.3 COGNITIVE ASSESSMENT OF YOUNG CHILDREN WITH ASD: ATTENTION AND INHIBITORY CONTROL. V. Grindell, C. Bloss and N. Akshoomoff*. Center for Autism Research, Children’s Hospital San Diego, University of California San Diego, San Diego, CA 92037. P2.5.4 EARLY SOCIAL COMMUNICATION, LANGUAGE, AND THEORY OF MIND IN CHILDREN WITH AUTISM SPECTRUM DISORDER. P. Warreyn and H. Roeyers. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium, B-9000 Slide Session 2: Topic 1: Face Processing I S2.1.1 FACE AND GAZE PROCESSING IN CHILDREN WITH AUTISM. R.M. Joseph, K. Ehrman, C. Connolly and H. Tager-Flusberg. Boston University School of Medicine, Boston, MA, 02118. S2.1.2 CAN PEOPLE WITH AUTISM FIND A FACE IN THE CROWD? C. Ashwin, S. Wheelwright and S. Baron-Cohen*. Autism Research Centre, Depts. of Experimental Psychology and Psychiatry, University of Cambridge, Cambridge UK CB2 2AH. S2.1.3 STRAIGHT GAZE ACCELERATES DETECTION, BUT DIRECT GAZE DOES NOT: THE CASE OF AUTISM. A. Senju, Y. Kunihira, T. Hasegawa and Y. Tojo. Dept. of Cognitive and Behavioral Science, Univ. of Tokyo, Tokyo, 153-8902, Japan. S2.1.4 PHENOTYPIC SUBTYPING OF INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS BASED ON PHYSIOLOGICAL INDICES OF AROUSAL PILOT DATA REPORT. S.S. Cohen, H.B. Perry, R.J. Hagerman* and D. Hessl*. M.I.N.D. Institute, University of California, Davis Medical Center, Sacramento, CA, 95817

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S2.1.5 ACTIVATION OF THE FUSIFORM GYRUS WHEN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER VIEW FACES. N. Hadjikhani, R.M. Joseph, C. Chabris, J. Clark, S. Steele, L. McGrath, M. Vangel, J. Snyder, I. Aharon, E. Feczko, G.J. Harris and H. Tager-Flusberg*. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. S2.1.6 FUNCTIONAL AND STRUCTURAL SUBSTRATES OF AFFECTIVE PROCESSING IN AUTISM: REFRAMING THE ORIGINS OF FUSIFORM HYPOACTIVATION. R.J. Davidson*, K.M. Dalton, B.M. Nacewicz, A.L. Alexander, M.A. Gernsbacher and H.H. Goldsmith. W.M. Keck Laboratory for Functional Brain Imaging and Behavior, Waisman Center, University of Wisconsin-Madison, 53705 Slide Session 2: Topic 2: Language Processing S2.2.1 FACIAL SPEECH PROCESSING IN CHILDREN WITH AUTISM. K. Condouris, R.M. Joseph, K. Ehrman, C. Connolly and H. Tager-Flusberg. Lab of Developmental Cognitive Neuroscience, Boston University School Of Medicine, Boston, MA, 02118-2526. S2.2.2 LIMITED EFFECTS OF LABELING ON COGNITIVE FLEXIBILITY IN CHILDREN WITH AUTISM. S. Jacques, N. Russo, T. Flanagan, O. Landry, D. Berringer and J.A. Burack. Dept. of Educ. Psych., McGill Univ., Montreal, QC, Canada H3A 1Y2. S2.2.3 LANGUAGE PROFILES IN HIGH-FUNCTIONING CHILDREN WITH ASD. T. Loucas, S. Chandler, G. Baird, T. Charman and E. Simonoff. A. Pickles. School of Medicine & Biomedical Sciences, King's College London, London SE1 3SS, United Kingdom.

S2.2.4 INTONATION AND CONTENT IN SARCASM UNDERSTANDING BY PARTICIPANTS WITH AUTISM, WITH AND WITHOUT LANGUAGE IMPAIRMENT. S. Pearlman-Avnion*; K. Condouris; L. Evancie, K. Ehrman and H. Tager-Flusberg. Lab of Developmental Cognitive Neuroscience, Boston Univ. Sch. Of Med., Boston, MA, 02118-2526. S2.2.5 EARLY LANGUAGE COMPREHENSION VIA PREFERENTIAL LOOKING. L. Swensen, E. Kelley, J. Latz, D. Fein and L. Naigles. Univ. of Conn., Storrs, CT 06269. Slide Session 2: Topic 3: Genetics II S2.3.1 DETECTION OF ALLELIC INTERACTION IN ASSOCIATION TO AUTISM: APPLICATION TO THE 15q12 GABAA RECEPTOR SUBUNIT REGION. J.L. McCauley, L.W. Hahn, E.R. Martin, J.H. Moore and J.S. Sutcliffe*. Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232 and Center for Human Genetics, Duke University, Durham, NC 27710. S2.3.2 INVESTIGATION OF GENE-GENE INTERACTIONS IN AUTISTIC DISORDER. A.E. Ashley-Koch, H. Mei, J. Jaworski, E.R. Martin, M.M. Menold, M. Cuccaro, J.R. Gilbert and M.A. Pericak-Vance *. Duke University Medical Center, Durham, NC, 27710. S2.3.3 A GENOMIC SCREEN AND EVIDENCE FOR GENE-GENE INTERACTION IN AUTISM. J.S. Sutcliffe*, L.M. Olson, S.E. Folstein, J.L. Haines and J.L. McCauley. Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232.

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S2.3.4 EVIDENCE SUPPORTING THE MULTIFACTORIAL THRESHOLD MODEL IN AUTISM. C. Wolpert 1, J. Grubber 1, S. Donnelly 1, H. Wright 2, J.R. Gilbert 1, M. Cuccaro 1, M.A. Pericak-Vance 1. 1 Center for Human Genetics, DUMC, Durham, NC 27710. 2 USC, Columbia, SC 29202 Slide Session 2: Topic 4: Early Intervention S2.4.1 INTERVENTION FOR INFANTS WITH AUTISTIC FEATURES: IMPLEMENTATION ISSUES. J. Brian 1*, S. Bryson 2, W. Roberts 1, P. Szatmari 3 and L. Zwaigenbaum 3. 1 Hospital for Sick Children/University of Toronto, ON, M5G 1X8; 2 Dalhousie/IWK, NS; 3 Hamilton Health Sciences/McMaster, ON, Canada. S2.4.2 TEACHING THE IMITATION AND SPONTANEOUS USE OF GESTURES IN YOUNG CHILDREN WITH AUTISM. B. Ingersoll* and L. Schreibman. Autism Research Program, Univ. of Calif., San Diego, CA 92093. S2.4.3 THE EFFECTS OF JOINT ATTENTION TRAINING ON LANGUAGE, PLAY, AND SOCIAL SKILLS IN YOUNG CHILDREN WITH AUTISM. C. Whalen.* University of Washington Autism Center, Seattle, WA 98195 and Schreibman, L. Autism Research Laboratory, University of California, San Diego 92093 S2.4.4 PERCEIVED RELATIONSHIPS WITH SERVICE PROVIDERS AMONG PARENTS OF CHILDREN WITH AUTISM. N.O. Davis, A.S. Carter* and J.C. Kuhn. Psych. Dept. UMass. Boston, Boston, MA 02125. S2.4.5 AUTISM AND STRONGER FAMILIES: AN EARLY INTERVENTION PERSPECTIVE. D. Keen, M. Braithwaite, S. Rodger and A. Jobling. University of Queensland, Brisbane, Queensland 4072, Australia

S2.4.6. PREDICTORS OF MATERNAL SELF-EFFICACY: PARENTING STRESS, GUILT, AGENCY, & AUTISM KNOWLEDGE. J.C. Kuhn*, A.S. Carter* and M. Belzince. Psych. Dept. UMass. Boston, Boston, MA 02125. Slide Session 2 Topic 5: Early Indicators in

Autism Spectrum Disorder

S2.5.1 VISUAL FIXATION DURING VIEWING OF NATURALISTIC SOCIAL SITUATIONS IN 2- TO 3-YEAR-OLD CHILDREN WITH AUTISM SPECTRUM DISORDERS. A.Klin*, W. Jones, K. Chawarska and F.R. Volkmar. Yale Child Study Center, New Haven, CT 06520. S2.5.2 RED FLAGS OF AUTISM SPECTRUM DISORDERS IN THE SECOND YEAR OF LIFE. A. Wetherby and J. Woods. FIRST WORDS Project, Florida State University, Tallahassee, FL 32306-7814. S2.5.3 REPETITIVE BEHAVIORS IN AUTISM ACROSS DEVELOPMENT. M. Cuccaro, S.L. Donnelly, R.K. Abramson, C.M. Wolpert, S.A. Ravan, H. Cope, H.H. Wright, A. Hall, R.L. Gabriels and M.A. Pericak-Vance*. Duke University, Durham, NC 27710. S2.5.4 REGRESSIVE AND NON-REGRESSIVE AUTISM: EFFECTS ON EARLY DEVELOPMENT. S.J. Rogers and S. Hepburn. Funded by *NICHD U19HD35468* one of the CPEA Network projects. carried out at Univ. Colo. Health Sciences Ctr, Denver, CO, 80262. S2.5.5 CHANGES IN RED FLAGS OF AUTISM SPECTRUM DISORDERS FROM THE SECOND TO THE THIRD YEAR OF LIFE. S. Shumway, A. Wetherby, J. Woods and N. Watt. FIRST WORDS Project, Florida State University, Tallahassee, FL 32306-7814.

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S2.5.6 OUTCOME AT 7 YEARS OF CHILDREN DIAGNOSED WITH AUTISM AT AGE 2. T. Charman*, E. Carter, A. Drew and G. Baird. Behavioural & Brain Sciences Unit. Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. t.charman@ich.ucl.ac.uk Slide Session 2: Topic 6: Special Symposium: Autism, Genes, and Environment Funded by NIEHS Chair: Isaac Pessah, Ph.D., Dept. of Molecular Biological Sciences, University of California, Davis Autism, Genes and Environment S2.6.1 PRENATAL EXPOSURE TO ENVIRONMENTAL NEUROTOXICANTS DYSREGULATES DEVELOPMENT OF THE SEROTONERGIC SYSTEM: RELEVANCE TO AUTISM? J.M. Lauder. Dept. of Cell and Developmental Biology. Univ. NC School of Medicine Chapel Hill, NC. S.2.6.2 LOSS OF NEUROPATHY TARGET ESTERASE IN MICE LINKS ORGANOPHOSPHATE EXPOSURE TO HYPERACTIVITY. C. Barlow (presenter), C.J. Winrow and J. Casida. The Salk Institute for Biological Studies and the University of California at Berkeley. S2.6.3 RESPIRATORY INFECTION IN PREGNANT MICE CAUSES BEHAVIORAL AND CEREBELLAR DEFECTS IN THEIR OFFSPRING RESEMBLING THOSE IN AUTISM. P.H. Patterson* and L. Shi. Biology Division, California Institute of Technology, Pasadena, CA 91125. S2.6.4 WHAT CULTURE MODELS TELL US ABOUT MERCURY NEUROTOXICITY. M. Aschner* and J.L. Aschner**. Departments of *Physiology and Pharmacology, and **Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC.

S2.6.5 GABAa RECEPTOR DEFICIENCY SIGNIFICANTLY POTENTIATES EXCITOTOXICITY OF NONCOPLANAR PCB 170 IN THE ACUTE HIPPOCAMPAL SLICE PREPARATION. K.H. Kim and I.N. Pessah*. Center for Children’s Environmental Health and Disease Prevention and M.I.N.D. Institute, University of California, Davis, CA 95616

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Slide Session 3 Topic 1: Face Processing II S3.1.1 FACE PROCESSING IN AUTISM: IS THERE PLASTICITY IN BRAIN ACTIVATION? S. Faja, E. Aylward, R. Bernier, M. Bloomquist and G. Dawson*. University of Washington, Box 357920, Seattle, WA 98185. S3.1.2 NORMAL ACTIVATION OF FUSIFORM GYRUS IN ADOLESCENTS AND ADULTS WITH AUTISM DURING VIEWING OF FAMILIAR FACES. E. Aylward, R. Bernier, K. Field, A. Grimme and G. Dawson*. University of Washington, Box 357115, Seattle, WA 98185. S3.1.3 FACE PROCESSING IS ALTERED IN AUTISM FAMILIES: BEHAVIORAL AND ERP EVIDENCE. G. Dawson*, S. Webb, S. Faja and M. Paul. University of Washington, Box 357920, Seattle, WA 98185. S3.1.4 ELECTROPHYSIOLOGICAL EVIDENCE OF DELAYED NEURAL PROCESSING OF FACES IN CHILDREN WITH AUTISM. S. Webb, R. Bernier, J. Shook, M. Paul and G. Dawson. University of Washington, Box 357920, Seattle WA, 98195. S3.1.5 THE FEFA: A COMPUTER-BASED PROGRAM TO TEST AND TO TEACH THE RECOGNITION OF FACIAL AFFECT. F. Poustka, S. Feineis-Matthews and S. Bölte. Department of Child and Adolescent Psychiatry, J.W.Goethe-University, Frankfurt/M, Germany. S3.1.6 FACE PROCESSING IN HIGH FUNCTIONING AUTISTIC ADULTS: A LOOK INTO SPATIAL FREQUENCIES AND THE INVERSION EFFECT. C. Rondan 1,2 and C. Deruelle 1. 1 Institute of Physiologic and Cognitive Neurosciences, CNRS, Marseille, France & 2 Laboratory of Psychology and Neurocognition, UMR 5105, CNRS, Grenoble, France

Slide Session 3: Topic 2: Neuropsychological

Processes S3.2.1 REDUCED LEFT INFERIOR FRONTAL AND ENHANCED OCCIPITAL ACTIVATION DURING SEMANTIC DECISION IN AUTISM: AN fMRI STUDY. M.S. Gaffrey (1), N. Kleinhans (2), F. Haist (3), and R-A. Müller (1,4)*. (1) Dept. of Psychology, San Diego State University; (2) JDP Clinical Psychology; Depts. Of (3) Psychiatry and (4) Cognitive Science, University of California, San Diego, CA 92120/92093. S3.2.2 PERCEPTUAL AND NEUROPHYSIOLOGICAL MEASURES OF AUDITORY FUNCTION IN CHILDREN WITH AUTISM DISORDER: AN MEG INVESTIGATION. N.M. Gage*, P. Fillmore, L. Isenberg, L. Mays and A. Spence. Univ of Calif, Irvine, Irvine, CA 92697 S3.2.3 DIMINISHED SEROTONIN RECEPTOR FUNCTION: A POTENTIAL ENDOPHENOTYPE OF AUTISM. J. Goldberg 1, P. Szatmari 2 and L. Zwaigenbaum 2. 1c'o Department Psychiatry and Behavioral Neurosciences, Chedoke Child and Family Centre, HHS, Hamilton. 2 McMaster University, Hamilton ON, Canada, L8N 3Z5 S3.2.4 REDUCED MODULATION OF COVERT ORIENTING REFLEXES IN HIGH FUNCTIONING ADOLESCENTS WITH AUTISM. G. Iarocci, J.A. Burack*, J.T. Enns, B. Randolph, and L. Mottron. Department of Psychology Simon Fraser University 8888 University Drive Burnaby, British Columbia V5A 1S6 S3.2.5 PREFRONTAL-LIMBIC DYSFUNCTION IN AUTISM. K.A. Loveland, J. Bachevalier and D.A. Pearson. Univ Texas Med Sch Houston TX 77030.

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S3.2.6 REDUCED OCCIPITO-FRONTAL FUNCTIONAL CONNECTIVITY DURING VISUOMOTOR PERFORMANCE IN AUTISM. M.E. Villalobos, A. Mizuno, B.C. Dahl and R-A. Müller *. Brain Development Imaging Lab, San Diego State University, San Diego, CA 92120. Slide Session 3: Topic 3: Genetics III S3.3.1 EVIDENCE THAT A NONVERBAL COMMUNICATION AUTISM ENDOPHENTOYPE IS LINKED TO CHROMOMSOME 3q25 AND ASSOCIATED WITH THE NEUROLIGIN-1 GENE IN THAT REGION. G. Chen, J.L. Stone, N. Kono, S.F. Nelson, D.H. Geschwindand and R.M. Cantor. Depts. of Human Genetics, and Neurology, UCLA School of Medicine, Los Angeles, CA 90024 S3.3.2 A GENETIC STUDY OF THE NEUROCOGNITIVE DEFICITS IN AUTISM. J. Hallmayer, D. Wong, A. Maley, W. Hill, D. Bishop and M. Maybery. Department of Psychiatry, Stanford University School of Medicine, Department of Psychology, University of Western Australia (UWA), and School of Psychiatry and Clinical Neurosciences, UWA. S3.3.3 STRATIFICATION OF AUTISM FAMILIES BASED ON SEX OF AFFECTED CHILDREN IDENTIFIES DISTINCT LINKAGE REGIONS. J.L. Stone, B. Merriman, R. Cantor, A. Yonan, AGRE Consortium, T.C. Gilliam, D.H. Geschwind and S.F. Nelson*. UCLA Human Genetics and Neurology departments, Los Angeles, CA 90095. S3.3.4 INTERGENERATIONAL TRANSMISSION OF AUTISTIC TRAITS: A STUDY OF TWINS AND THEIR PARENTS. J.N. Constantino*, and R.D. Todd*. Social Developmental Studies Program, Washington University School of Medicine, St. Louis, MO 63110, USA.

S3.3.5 SCREENING FOR THE AUTISM SPECTRUM IN A STATEWIDE TWIN SAMPLE. H.H. Goldsmith, M.A. Gernsbacher, E.K. Kees and C.A. Van Hulle. Waisman Center & Department of Psychology, Univ. of Wisconsin, Madison, WI. 53706. Slide Session 3 Topic 4: School Age

Intervention S3.4.1 SYSTEMIZING EMPATHY: TEACHING ADULTS WITH ASPERGER SYNDROME TO RECOGNIZE COMPLEX EMOTIONS. O. Golan and S. Baron-Cohen*. Autism Research Centre, Departments of Experimental Psychology and Psychiatry, Cambridge University, 18b Trumpington Road, Cambridge, CB2 2AH, U.K. S3.4.2 THE EFFECTIVENESS OF RELATIONSHIP DEVELOPMENT INTERVENTION IN REMEDIATING DEFICITS IN INTER-SUBJECTIVE ENGAGEMENT IN AUTISM-SPECTRUM CHILDREN. S.E. Gutstein. The Connections Center for Family and Personal Development, Houston, Texas 77025 S3.4.3 PROPOSED USE OF TWO-PART INTERACTIVE MODELING TO ENGENDER EMPTHAY IN CHILDREN WITH AUTISM. D. Sherman and I.M. Pepperberg. Psychol. Dept, Brandeis University, Waltham, MA 02454; MIT School of Architecture and Planning, Cambridge, MA 02139; New-Found Therapies, Monterey, CA 93940. S3.4.4 A COGNITIVE-BEHAVIORAL INTERVENTION WITH PARENT COACHING FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS. M. Solomon, Ph.D. and B. Goodlin-Jones, Ph.D. Department of Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UCDHS, 2825 50th Street, Sacramento, CA 95817 Sponsor: Children’s Miracle Network*

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S3.4.5 EFFICACY OF FATHER-FOCUSED PARENT TRAINING FOR FATHERS OF CHILDREN WITH AUTISM. J.M. Winter* and L. Schreibman. Autism Research Laboratory, Univ. of California, San Diego, Dept. of Psychology 0109, La Jolla, CA 92093-0109. Slide Session 3: Topic 5: Biological Aspects in

Early Development S3.5.1 ACCELERATED HEAD GROWTH DURING EARLY DEVELOPMENT AND RISK FOR AUTISTIC DISORDER. Y.A. Dementieva 1,2, D.D. Vance 1, S.L. Donnelly 1, C.M. Wolpert 1, S.A. Ravan 3, R.K. Abramson 3, H.H. Wright 3, M. Cuccaro* 1, 4. 1Center for Human Genetics, Duke University Medical Center, Durham, NC 27710. 2Division of Math. & Applied Science, Marshall University, Huntington, WV 25755. 3W.S. Hall Psychiatric Institute, University of South Carolina, Columbia, NC 29208. 4Division of Psychiatry, Duke University. Medical Center, Durham, NC 27710 S3.5.2 PATHOLOGICAL BRAIN OVERGROWTH LEADS TO REDUCED INTERHEMISPHERIC CONNECTIVITY. J.D. Lewis and E. Courchesne. Center for Autism Research, Children's Hospital Research Center, San Diego, CA, 92037 S3.5.3 MERCURY LEAD AND ZINC LEVELS IN BABY TEETH OF CHILDREN WITH AUTISM. .J. Romdalvik and J.B. Adams.Arizona State University, Tempe, AZ 85287-6006. V.M.S. Ramanujam and M. Lagatore. U. of Texas Medical Branch, Galveston, TX 88555-1110 S3.5.4 SEROTONERGIC DYSFUNCTION AND BEHAVIORAL CHANGE IN THE EMBRYONAL THALIDOMIDE/VALPROIC ACID EXPOSED AUTISM MODEL RATS. N. Narita*, M. Tazoe and M. Narita. Inst. of Basic Med. Sci., U of Tsukuba. Tsukuba, Ibaraki, 305-8575, Japan.

S3.5.5 WIDESPREAD SIMILAR CORTICAL ASYMMETRIES IN AUTISM AND DEVELOPMENTAL LANGUAGE DISORDER ARE MOST PROMINENT IN HIGHER-ORDER ASSOCIATION AREAS. M. Herbert1,2,6, D. Ziegler1,2,

C. Deutsch4,5,7, L. O’brien8, D. Kennedy1,2,3, P. Filipek9, A. Bakardjiev10, J. Hodgson11, M. Takeoka12, N. Makris1,2, V. Caviness Jr.1,2 1Center for Morphometric Analysis, and Departments of 2Neurology and 3Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 4Department of Psychiatry, Harvard Medical School, Boston, MA; 5Psychobiology and Medical Genetics Programs, Eunice Kennedy Shriver Center, Waltham, Massachusetts; Departments of 6Neurology and 7Mailman Research Center, McLean Hospital, Belmont, MA; 8Department of Mathematics, Colby College, Waterville, ME; 9Department of Pediatrics, University of California, Irvine; 10Department of Infectious Diseases, Children’s Hospital Oakland; 11Augsburg College, Minneapolis, MN; 12Children’s Hospital, Boston, MA. Slide Session 3: Topic 6: The Development of

Young Siblings of Children with Autism

S3.6.1 FACE-TO-FACE INTERACTION OF INFANT SIBLINGS OF AUTISTIC CHILDREN: AN EXPLORATORY STUDY OF PATTERNS OF MUTUAL GAZE, SMILING AND VOCALIZATION. M. Gratier and A. Dijamco. Dept. of Psychology, 2279 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095 S3.6.2 TEMPERAMENT IN INFANTS LATER DIAGNOSED WITH AUTISM. S.E. Bryson, L. Zwaigenbaum, J. Brian, W. Roberts, P. Szatmari and C. McDermott. Autism Research Unit, Hospital for Sick Children, Toronto, ON M5G 1X8. Funded by NAAR and CIHR. S3.6.3 BEHAVIORAL MARKERS OF AUTISM IN HIGH-RISK 12-MONTH-OLDS. L. Zwaigenbaum,

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S.E. Bryson, J. Brian, W. Roberts, C. McDermott and P. Szatmari. Department of Pediatrics, McMaster University. Evel 4 PO Box 2000 Hamilton, Ontario, Canada, L8N 3Z5 S3.6.4 THE DEVELOPMENT OF SIBLINGS OF CHILDREN WITH AUTISM: SOCIAL ENGAGEMENT AT 4 MONTHS. N. Yirmiya*, I. Gamliel, M. Sigman*, R. Feldman, T. Pilowsky and S. Baron-Cohen. Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem, ISRAEL 91905. S3.6.5 RESPONSE TO JOINT ATTENTION AT 14 AND 24 MONTHS IN AUTISM SPECTRUM DISORDER: A LONGITUDINAL STUDY. M.T. Sullivan*, R. Landa, C. Taylor. Center for Autism & Related Disorders, KKI, Balt, MD 21211 Poster Session 3: Topic 1: Biological Markers In

Early Development. P3.1.1 A COMPARATIVE INVESTIGATION OF GROWTH PATTERNS DURING THE FIRST THREE YEARS OF LIFE OF INFANTS WITH HIGH-FUNCTIONING AUTISM AND ASPERGER'S DISORDER. C. Dissanayake 1, Q. Bui 2, D. Loesch 1 and R. Huggins 2. 1School of Psychological Science and 2School of Statistical Science, La Trobe University, Victoria 3086, AUSTRALIA, P3.1.2 IMPACT OF ENVIRONMENTAL FACTORS ON BRAIN DEVELOPMENT AND BEHAVIOR IN MALES AND FEMALES. E.M. Sajdel-Sulkowska 1,2,* K. Nguon 2, B. Ladd 2, M.G. Baxter 3. 1Harvard Med. Sch., 2BWH, 3Harvard U., Boston, MA 02115 P3.1.3 BEHAVIORAL SENSITIVITY TO METHYLMERCURY FOLLOWING PRENATAL OR EARLY POSTNATAL EXPOSURE. A.K. Halladay 1,3, G.C. Wagner 2,3 and K.R. Reuhl 1,3, 1Departments of Pharmacology and Toxicology, and 2Psychology, 3Rutgers University, New Brunswick,

NJ and the Center for Neurotoxicology and Exposure Assessment P3.1.4 MOLECULAR AND CELLULAR BASIS OF SEROTONERGIC DYSFUNCTION IN THE EMBRYONAL THALIDOMIDE/VALPROIC ACID EXPOSED AUTISM MODEL RATS. M. Narita*, M. Tazoe, and N. Narita. Inst. of Basic Med. Sci., U of Tsukuba. Tsukuba, Ibaraki, 305-8575, Japan. P3.1.5 GABRB3 GENE EXPRESSION IN DEVELOPING MOUSE BRAIN. T.M. DeLorey*, T. Wei, E. Hashemi and O. Mateeva. Molecular Research Institute, Mountain View, CA 94043 Poster Session 3: Topic 2: Joint Attention, Play

and Social Development

P3.2.1 DEVELOPMENT OF SOCIAL BEHAVIOR OF CHILDREN WITH AUTISM: NATURALISTIC OBSERVATIONS IN THE CLASSROOM ENVIRONMENT. A. Dijamco, L. Travis and M. Sigman*. University of California, Los Angeles; Los Angeles, CA 90024. P3.2.2 VALIDITY INVESTIGATION OF TWO MEASURES OF PERSEVERATIVE OBJECT USE IN YOUNG CHILDREN WITH AUTISM. C. Taylor*, and P. Yoder. Vanderbilt University. P3.2.3 THE RELATIONSHIP BETWEEN EXPRESSIVE/RECEPTIVE LANGUAGE ABILITIES AND RESPONDING TO THE JOINT ATTENTION BIDS OF OTHERS AND INITIATING JOINT ATTENTION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. D. Murray, N. Creaghead, P. Manning-Courtney, J. Bean, P. Shear and J. Prendeville. University of Cincinnati and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. 45229. P3.2.4 CORRELATES AND PREDICTORS OF PEER INTERACTION IN AUTISTIC SPECTRUM

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DISORDER. H. Schmidt*, C. Lord and S. Risi. University of Michigan Autism and Communication Disorder Center, University of Michigan, Ann Arbor, MI 48109. P3.2.5 IMMEDIATE AND DEFERRED IMITATION OF CHILDREN WITH AUTISM. C.C. Wu and C.H. Chiang. Department of Psychology, National Chung Cheng University. 160, San-Hsing, Ming-Hsung, Chia-Yi 621, Taiwan R.O.C. P3.2.6 PARENTAL REPORTS OF THE EMPATHIC BEHAVIOUR OF YOUNG CHILDREN WITH AUTISM, DOWN SYNDROME, AND TYPICAL DEVELOPMENT. K. Hudry and V. Slaughter. Early Cognitive Development Unit, School of Psychology, University of Queensland, Brisbane, Australia, 4072. P3.2.7 THE CONTRIBUTIONS OF COGNITIVE ABILITY, SOCIAL RECIPROCITY, AND MOTOR SKILLS TO IMITATION PERFORMANCE IN CHILDREN WITH ASD. L. Turner, W. Stone* and T. Ulman. Vanderbilt University, Nashville, TN, 37232. P3.2.8 THE IMPORTANCE OF CONTEXT IN SOCIAL RESPONSIVITY AND INITIATION. C. Shulman and E. Kanfi. School of Social Work, The Hebrew University of Jerusalem. P3.2.9 THE PATTERNS OF SOCIAL GAZING AND THEIR INTENTIONAL COMMUNICATION IN YOUNG CHILDREN WITH AUTISM. C.H. Chiang 1 and W.T. Soong 2. 1Department of Psychology, National Chung Cheng University. 160, San-Hsing, Ming-Hsung, Chia-Yi 621, Taiwan R.O.C.; 2Department of Psychiatry, Institutes of Psychology and Epidemiology. National Taiwan University. 7 Chung-San South Rd., Taipei 100, Taiwan R. O. C. P3.2.10 A LONGITUDINAL ANALYSIS OF PRETEND PLAY IN AUTISM. M.D. Rutherford, S.J.

Rogers and S. Hepburn. University of Colorado, Health Sciences Center., Denver, CO 80262. P3.2.11 SOCIAL ORIENTING AS A CONSTRUCT UNDERLYING JOINT ATTENTION AND OTHER SKILL DEFICITS IN A SAMPLE OF PRESCHOOL CHILDREN WITH AUTISM. S.B. Reavis, M.A. Mesibov and G.B. Mesibov, Ph.D.* University of North Carolina at Chapel Hill, Chapel Hill, NC 27502. P3.2.12 JOINT ATTENTION BEHAVIORS IN CHILDREN WITH AUTISM: STABILITY AND CHANGE DURING THE PRESCHOOL YEARS . M. Siller and M. Sigman*. Department of Psychology, University of California at Los Angeles, Los Angeles, CA 90024. P3.2.13 STRUCTURED VS. NATURALISTIC OBJECT IMITATION IN YOUNG CHILDREN WITH ASD. W. Stone*, T. Ulman, A. Swanson, C. McMahon and L. Turner. Vanderbilt University, Nashville, TN, 37232. P3.2.14 SLIGHTLY DIFFERENT MECHANISMS OF IMITATION BETWEEN CHILDREN WITH AND WITHOUT AUTISM. Y. Kunihira, A. Senju, T. Hasegawa and Y. Tojo. Dept. of Cognitive and Behavioral Science, Univ. of Tokyo. Tokyo, 153-8902, Japan. P3.2.15 PERCEPTUAL CAUSALITY IN YOUNG CHILDREN WITH AUTISM. A. Schlottmann and E.D. Ray. Dept of Psych, Univ College London. P3.2.16 LONGITUDINAL RELATIONS BETWEEN PLAY AND GESTURE BEHAVIORS IN INFANTS WITH AUTISM. L.R. Watson, G.T. Baranek, E.R. Crais, E. Collins, J. Dykstra and V. Poston. Univ. N. Carolina, Chapel Hill, NC 27599.

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Poster Session 3: Topic 3: Microbiology and

Immunology of Autism Spectrum Disorder

P3.3.1 FAMILIAL AUTOIMMUNITY AS A RISK FACTOR FOR REGRESSION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. C.A. Molloy, A.L. Morrow, J. Meinzen-Derr and C. Lord. Collaborative Programs of Excellence in Autism and Cincinnati Children’s Hospital Medical Center Univ of Cincinnati Coll of Med., Cincinnati, OH 45229. P3.3.2 IMMUNE PHENOTYPES IN AUTISM SPECTRUM DISORDER. J. Meinzen-Derr, C.A. Molloy, A.L. Morrow and M. Wills-Karp. Cincinnati Children’s Hospital Medical Center. Cincinnati, Ohio, 45229. Poster Session 3: Topic 4: Perception, Attention,

Learning and Memory P3.4.1 THE EXAMINATION AND TRAINING OF MEMORY STRATEGIES IN CHILDREN WITH AUTISM. J. Bebko and T. Rhee. Department of Psychology, York University, Toronto, Ontario, Canada M3J 1P3 P3.4.2 IMPAIRED AUDITORY PROCESSING IN YOUNG CHILDREN WITH AUTISM: AN ERP STUDY. M.D. Bomba, W.J. Logan, W. Roberts and E.W. Pang*. Division of Neurology, Hospital for Sick Children, Toronto, Canada, M5G 1X8. P3.4.3 SUPERIOR DISEMBEDDING IN INDIVIDUALS WITH AUTISM AND THEIR PARENTS: THE NEED OF SUBTLE MEASURES. M.V. de Jonge, C. Kemner and H. van Engeland*. Univ. of Utrecht, Depart. Of Child and Adolesc. Psych., Utrecht 3508 GA, The Netherlands

P3.4.4 LOCAL VERSUS GLOBAL PLANNING IN NARRATIVES BY CHILDREN WITH AUTISM. J.J. Diehl, L. Bennetto* and J.E. Arnold. Depts. of Clinical & Social Sciences in Psychology, and Brain & Cognitive Sciences, Univ. of Rochester, Rochester, NY 14627. P3.4.5 THE RELATIONSHIP BETWEEN NEUROPSYCOLOGICAL MEASURES OF COGNITIVE FLEXIBILITY AND STEREOTYPED. AND REPETITIVE BEHAVIOR IN CHILDREN WITH AUTISM SPECTRUM DISORDERS. M.C. Gibbs, P. Lee, L. Gilotty, G. Wallace, D. Black and L. Kenworthy*. Center for Autism Spectrum Disorders, Children’s National Medical Center, Washington, DC 20010. P3.4.6 EARLY VISUAL CORTEX ORGANIZATION IN AUTISM: AN fMRI STUDY. N. Hadjikhani, C. Chabris, R.M. Joseph, J. Clark, L. McGrath, I. Aharon, E. Feczko, H. Tager-Flusberg*, G.J. Harris. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. P3.4.7 COGNITIVE FUNCTIONING AND ASPERGER’S DISORDER: GIRLS VS BOYS. A.V. Hall, PhD., R.K. Abramson, PhD., S.A. Ravan, MS, H.H. Wright, MD* University of South Carolina School of Medicine, Columbia, SC, 29203 and M. Cuccarro, PhD. Duke University, Center for Human Genetics, Durham, NC, 79910. P3.4.8 EFFECTS OF RELATED AND UNRELATED CONTEXT ON MEMORY IN ASPERGER'S SYNDROME. D.M. Bowler, J.M. Gardiner and S.B. Gaigg. Department of Psychology, City University, London EC1V 0HB, UK

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P3.4.9 A FUNCTIONAL MRI STUDY OF RESPONSE INHIBITION IN AUTISM. R.K. Kana, T.A. Keller, M.A. Just* and N. Minshew+. Center for Cognitive Brain Imaging, Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213. +Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260. P3.4.10 EARLY VISUAL PERCEPTION IN INDIVIDUALS WITH AUTISM AND THEIR PARENTS. C. Kemner, M.V. de Jonge and H. van Engeland*. Univ. of Utrecht, Depart. Of Child and Adolesc. Psych., Utrecht 3508 GA, The Netherlands P3.4.11 MINOR PHYSICAL ANOMALIES IN AUTISM AND IN MENTAL RETARDATION. M.M. Konstantareas, and E. Cooper. Department of Psychology, College of Social and Applied Human Scinces, University of Guelph, Guelph, Ont. Canada. P3.4.12 PATTERNS OF PERFORMANCE ON THE LEITER-R IN YOUNG CHILDREN WITH AUTISM SPECTRUM DISORDERS, NON-AUTISM DEVELOPMENTAL DELAYS, AND TYPICAL DEVELOPMENT. E.S. Kuschner, L. Bennetto* and K. Yost. Univ. of Rochester, Dept. of Clinical & Social Psychology, Rochester, NY 14627. P3.4.13 PERFORMANCE ON CANTAB SUBTESTS SENSITIVE TO FRONTAL LOBE FUNCTION IN PEOPLE WITH AUTISTIC DISORDER: EVIDENCE FROM THE CPEA NETWORK. S. Ozonoff *, H. Coon, G. Dawson, R.M. Joseph, A. Klin, W.M. McMahon, N. Minshew, J.A. Munson, B.F. Pennington, S.J. Rogers, A. Spence, H. Tager-Flusberg and F.R. Volkmar. M.I.N.D. Institute, UC Davis, Sacramento CA 95817. P3.4.14 RESPONSE INHIBITION AND STATE REGULATION IN CHILDREN WITH HFA AND ADHD. R. Raymaekers, I. Antrop, H. Roeyers, J.J. van der Meere, J.R. Wiersema, S. Verté and D. Baeyens. Department of Experimental Clinical and

Health Psychology, Ghent University, Ghent, Belgium, B-9000 P3.4.15 IS THERE A REGRESSIVE PHENOTYPE OF AUTISM SPECTRUM DISORDER ASSOCIATED WITH THE MEASLES-MUMPS-RUBELLA VACCINE? J. Richler, R. Luyster, S. Risi, C. Lord* and Collaborative Programs for Excellence in Autism. P3.4.16 EXECUTIVE FUNCTIONS IN AUTISM AND OTHER DEVELOPMENTAL DISORDERS. H. Roeyers (1), S. Verté (1), H. Geurts (2), J. Oosterlaan (2) and J.A. Sergeant (2). (1)Ghent University, Department of Experimental-Clinical and Health Psychology, Gent, Belgium; (2)Vrije Universiteit, Department of Clinical Neuropsychology, Amsterdam, The Netherlands P.3.4.17 IMPAIRED CATEGORICAL PERCEPTION IN AUTISM: AN ABNORMAL TOP-DOWN EFFECT. I. Soulières, L. Mottron, D. Saumier, and S. Larochelle. Clinique spécialisée de l’autisme, Hôpital Rivière-des-Prairies, Montréal, QC, CAN, H1E 1A4. P3.4.18 INCREASED NON-RIGHT (LEFT) HANDEDNESS IN AUTISTIC INDIVIDUALS, THEIR PARENTS AND SIBLINGS. S.J. Spence, N. Gitcho, L.J. Sterling, C.M. Lajonchere and D.H. Geschwind*. Departments of Psychiatry & Neurology, David Geffen School of Medicine at UCLA and the Autism Genetic Resource Exchange, L.A., CA, 90095. P3.4.19 SPATIAL WORKING MEMORY DEFICIT IN AUTISM. S. Steele*, N. Minshew, B. Luna, and J.A. Sweeney. Cntr. for Cog. Med., UIC, Chicago, IL 60612 and Dept. of Psychiatry, Univ. of Pitt., Pittsburgh, PA 15213.

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Poster Session 3: Topic 5: Neuropathology and

Basic Studies P3.5.1 METABOLOMICS IN AUTISM. B. Evans, J. Evans and O. Koul*. Department of Biochemistry and Molecular Pharmacology, UMass Medical Center, and Shriver Center, 200 Trapelo Road, Waltham, MA 02452. P3.5.2 NEUROPATHOLOGICAL CORTICAL AND CEREBELLAR ARCHITECTURAL ABNORMALITIES IN A CASE OF AUTISM. C.J. McDermott, A. Dean, A. Bailey and P. Luthert*. Institute of Ophthalmology, UCL, London. EC1V 9EL; University of Cambridge, Addenbrooke’s NHS Trust, Cambridge CB2 2QQ, UK; University of Oxford, Warneford hospital, Oxford, OX3 7JX, UK. P3.5.3 A NEUROPATHOLOGICAL INVESTIGATION OF THE BRAINSTEM IN AUTISM. S. Thevarkunnel, M. Martchek, G.J. Blatt*, T.L. Kemper* and M.L. Bauman*. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118. P3.5.4 CELL PACKING DENSITY IN THE INFERIOR OLIVE IN AUTISM. M.A. Ward, M.L. Bauman* and T.K. Kemper. Massachusetts General Hospital, Boston, MA and Boston University School of Medicine, Boston, MA. 02118 P3.5.5 IMMUNOCYTOCHEMICAL ANALYSIS OF INTERNEURONS IN THE CEREBRAL CORTEX OF AUTISTIC PATIENTS. E. López-Hurtado and J.J. Prieto. Dept. Histology and Anatomy, Univ. Miguel Hernández, 03550-Alicante, Spain. P3.5.6 CALBINDIN D-28K IS A RELIABLE MARKER FOR CEREBELLAR PURKINJE CELLS IN CONTROL AND AUTISTIC CEREBELLUM. E.R. Whitney, T.L. Kemper, M.L. Bauman, G.J. Blatt*.

Boston University School of Medicine, Department of Anatomy and Neurobiology. Boston, MA 02118 P3.5.7 DENSITY AND DISTRIBUTION OF 125[I] LABELED 5-HT2A/2C RECEPTORS IN THE ANTERIOR CINGULATE CORTEX IN CONTROL AND AUTISTIC INDIVIDUALS. E. Antzoulatos and G.J. Blatt. Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, MA. P3.5.8 ENDOCRINE DISRUPTOR CHEMICALS: A POSSIBLE CAUSE OF AUTISM AND OTHER DEVELOPMENTAL BRAIN DISORDERSGENE EXPRESSION RESEARCH. Y-I. Kuroda. Tokyo Metropolitan Institute for Neuroscience, 2-6, Musashidai,Fuchu-shi, Tokyo183-8526, Japan. P3.5.9 ALTERED CEREBRAL CORTICAL SPINE DENSITIES CHARACTERIZE A SUBGROUP OF INDIVIDUALS WITH AUTISM. H. Zhang and J. Hutsler *. Psychology Department and Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109-1109 P3.5.10 STEREOLOGICAL STUDY OF THE DEEP CEREBELLAR NUCLEI IN RATS EXPOSED TO VALPROIC ACID IN UTERO. T.L. Arndt, B.A. Tisdale, C.J. Stodgell, J.L. Ingram and P.M. Rodier*. Univeristy of Rochester School of Medicine and Dentistry, Rochester, New York, 14642. P3.5.11 DYNAMIC EXPRESSION OF MECP2 IN THE DEVELOPING MOUSE BRAIN. D. Braunschweig, T. Simcox, R.C. Samaco and J.M. LaSalle. Medical Microbiology and Immunology, Rowe Program in Human Genetics, UC Davis, CA, 95616

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Poster Session 3: Topic 6: Descriptive and

Diagnostic P3.6.1 PERCEPTIONS OF CHANGING NEEDS OF CHILDREN WITH AUTISM AMONG EDUCATORS IN SOUTH CAROLINA. J. Charles, L.M. Arnstein*, J. Nicholas, L.B. King, R. Brown and W.H. Jenner. Medical University of South Carolina, Charleston, SC 29414. P3.6.2 DEVELOPING A CLINICIAN-FRIENDLY ASSESSMENT TOOL FOR A NATURALISTIC BEHAVIORAL INTERVENTION. M. Rocha, S. Dufek*, L. Schreibman and A. Stahmer. Autism Research Laboratory, University of California, San Diego 9500 Gilman Drive La Jolla, CA 92093-0109 P3.6.3 LONG-TERM OUTCOMES OF CHILDREN WITH AUTISM SPECTRUM DISORDERS: A 5-YEAR FOLLOW-UP STUDY. B.J. Ivers*, R.L., Gabriels, L.G. Ogden and D.E. Hill. University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 P3.6.4 DEVELOPMENT OF THE JOINT ATTENTION MEASUREMENT SCALE AND RESULTS OF SCALE RELIABILITY FROM PILOT DATA. K.A. Kerchner, C. Blevins and C.J. Claflin* Northwest Missouri State University 800 University Dr. Maryville, MO 64468 P3.6.5 THE EFFECT OF HIGH AND LOW STRUCTURED CLASSROOM ACTIVITIES ON THE SOCIAL BEHAVIOR OF CHILDREN WITH AUTISM. A.C. Morgan and B. D’Entremont. University of New Brunswick, Fredericton, New Brunswick, Canada, E3B 2Y1

P3.6.6 EDUCATIONAL PLACEMENT OF CHILDREN WITH AUTISM: RESULTS FROM A LONGITUDINAL STUDY. R.S. Oti, C. Lord*, S. Risi, C. Carlson and D. Anderson. University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109. Poster Session 3: Topic 7: Families P3.7.1 INFLUENCES ON MATERNAL AND FAMILY FUNCTIONING IN CHILDREN WITH AUTISM SPECTRUM DISORDERS. S. Bishop, C. Lord, S. Risi, S. Qiu, D. Anderson. University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109. P3.7.2 PERSONALITY AND PSYCHOPATHOLOGY IN RELATIVES OF SUBJECTS WITH AUTISM. S Bölte and F. Poustka. Department of Child and Adolescent Psychiatry. J.W.Goethe-University, Frankfurt/M, Germany. P3.7.3 SOCIAL-EMOTIONAL DIFFERENCES IN HIGHER FUNCTIONING CHILDREN WITH AUTISM. C. Burnette, D. Charak and P.C. Mundy*, Department of Psychology, University of Miami, Coral Gables, FL, 33146. P3.7.4 CAREGIVER STRESS AND CONCERNS AS RELATED TO AUTISM FEATURES. D.E. Hill, R.L. Gabriels*, L.G. Ogden, B.J. Ivers.*University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 P3.7.5 PARENT PERCEPTIONS ON THE CONGENITAL VS. REGRESSIVE ONSET OF AUTISM AND ITS RELATION TO PARENTAL AFFECTIVE PSYCHOPATHOLOGY. R.P. Goin and B.J. Myers. Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284.

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P3.7.6 NEUROPSYCHOLOGICAL FUNCTIONING OF SIBLINGS OF CHILDREN WITH AUTISM. T. Pilowsky, N. Yirmiya, V. Gross-Tsur and R.S. Shalev. Hebrew University of Jerusalem, Jerusalem, Israel 91905; Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel 91031. P3.7.7 THE SECOND CRISIS: PARENTING A PREPUBESCENT CHILD WITH AUTISTIC SPECTRUM DISORDER. M. Souders, J. Bloch, E. Giarelli, J. Pinto-Martin, S. Levy and PA-CADDRE. P3.7.8 FACTORS ASSOCIATED WITH THE BEHAVIORAL AND EMOTIONAL ADJUSTMENT OF SIBLINGS OF CHILDREN WITH ASD. A. Weissman*, B.A., J. Pinto-Martin, MPH, Ph.D. and the PA-CADDRE; Univ. of Penn., Philadelphia, PA 19104 P3.7.9 DESCRIPTIVE ANALYSIS OF FAMILIES OF AUTISTIC CHILDREN WITH SEIZURES. L.W. Wang and S.J. Spence.* David Geffen School of Medicine at UCLA, L.A., CA 90024. Slide Session 4: Topic 1: Theory of Mind S4.1.1 ATTACHMENT AND FRIENDSHIP IN AUTISM. N. Bauminger, S.J. Rogers and M. Solomon. Bar Ilan Univ. Sch. Of Education, Ramat Gan, Israel 52900. S4.1.2 IMPAIRED COMMUNICATION IN AUTISM: THE ROLE OF IDENTIFICATION. P. Hobson, T. Lee and J. Meyer. Developmental Psychopathology Research Unit University College London and Tavistock Clinic 120 Belsize Lane London NW3 5BA UK

S4.1.3 EMPATHISING AND SYSTEMISING IN ADULTS WITH AND WITHOUT ASPERGER SYNDROME. J. Lawson, S. Baron-Cohen* and S. Wheelwright. University of Cambridge, Autism Research Centre, Department of Psychiatry, Douglas House, Trumpington Road, Cambridge, CB2 2AH, U.K. S4.1.4 AUTISM AND THE ROLE OF “CULTURAL KNOWLEDGE” IN USING THEORY OF MIND IN PRACTICE. E. Loth 1,2*, J.C. Gómez 2. 1SGDP Centre, Inst of Psychiatry, London, SE58AF, U.K. 2School of Psychology, Univ of St Andrews, KY169JU, Scotland S4.1.5 SELF-OTHER ORIENTATION IN AUTISM. J. Meyer and P. Hobson. Developmental Psychopathology Research Unit, University College London and Tavistock Clinic, 120 Belsize Lane, London NW3 5BA UK S4.1.6 MIND-READING IN YOUNG ADULTS WITH A PERVASIVE DEVELOPMENTAL DISORDER: DOES STRUCTURE MATTER? K. Ponnet, H. Roeyers, A. Buysse and A. De Clercq. Department of Clinical Psychology, Research Group, Developmental Disorders, Ghent University, H. Dunantlaan 2, B-9000 Gent, Belgium, Phone: +32-9-264 91 05 ; Fax: 32-9-264 64 89. Slide Session 4: Topic2: Cognitive Processes S4.2.1 DECISION-MAKING DURING A SIMULATED GAMBLING TASK IN ASPERGER’S DISORDER. S.A. Johnson*, E. Yechiam, R.R. Murphy, H.L. Coates, P. Theiner-Schumacher, J.D. Lutgring, R.E. Burt, and J. Stout. Clinical & Cognitive Neuroscience Lab, Indiana University, Bloomington, IN, 47405.

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S4.2.2 POOR INHIBITION OF DISTRACTERS IN POP-OUT COUNTING: EVIDENCE FOR IMPAIRED ATTENTION IN AUTISM. M. Knobel and K. Boser. Johns Hopkins Univ., Baltimore, MD., 21287. S4.2.3 ARE PEAKS OF ABILITY REFLECTING A "G" FACTOR IN PERSONS WITH AUTISM? L. Mottron*, M. Dawson, C. Bertiaume, I. Soulière. Clinique spécialisée de l'autisme, Hôpital Rivière des Prairies, 7070 Bvd Perras, Montréal, Québec, Canada, H1E1A4. S4.2.4 DEGREE OF GLOBAL / LOCAL PROCESSING IS RELATED TO COHERENT MOTION DETECTION. E. Milne*, J.Swettenham, R. Campbell and M. Coleman. Dept. Hum.Comm.Sci, UCL, London, WC1 1PF, UK. S4.2.5 DO BOYS WITH ASPERGER SYNDROME HAVE A NARROWING OF ATTENTIONAL FOCUS? EVIDENCE FROM BOUNDARY EXTENSION. P. Mitchell, D. Ropar and P. Chapman. School of Psychology, University of Nottingham, UK. S4.2.6 FREQUENCY SELECTIVITY IN AUTISM AND ASPERGER'S SYNDROME. E.J. Weisblatt and J.I. Alcántara. Departments of Psychiatry and Experimental Psychology, University of Cambridge, Cambridge UK, CB2 2AH Slide Session 4: Topic 3: Genetics IV S4.3.1 ALTERATION OF IMPRINTED GENE EXPRESSION IN RETT SYNDROME AND IN THE Mecp2-KNOCKOUT MOUSE. L.B.K. Herzing 1* and D.H. Ledbetter 2. 1Dept of Pediatrics, Northwestern University, Chicago IL 606141. 2Dept of Human Genetics, Emory University, Atlanta GA 303222.

S4.3.2 EPIGENETIC ALTERATION OF ANGELMAN SYNDROME GENE IN AUTISM BRAINS. Y-H. Jiang, Q. Liu and A.L. Beaudet. Dept. of Molecular & Human Genetics. Baylor College of Medicine. Houston TX 77030 S4.3.3 MECP2 EXPRESSION IN POSTNATAL BRAIN IS AFFECTED BY CELL EXTRINSIC FACTORS. J.M. LaSalle, D. Braunschweig, T. Simcox and R.C. Samaco. Med Micro and Immuno, Rowe Program in Hum. Genet, UCD, Davis, CA, 95616 S4.3.4 MECP2 EXPRESSION DEFECTS IN THE CEREBRAL CORTEX OF AUTISM PATIENTS MAY BE A RESULT OF BOTH TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS. R.P. Nagarajan, R.C. Samaco, D. Braunschweig and J.M. LaSalle*. Medical Microbiology & Immunology, UC Davis Sch. Med., Davis, CA 95616 S4.3.5 AUTISM IN ANGELMAN SYNDROME: IMPLICATIONS FOR AUTISM RESEARCH. S.U. Peters, A.L. Beaudet*, N.S. Madduri and C.A. Bacino. Depts. of Pediatrics & Mol. & Human Genetics, Baylor College of Medicine, Houston, TX 77030 S4.3.6 MOLECULAR CHARACTERIZATION OF 15Q11-Q13 DUPLICATIONS INVOLVED IN AUTISM BY HIGH RESOLUTION COMPARATIVE GENOMIC HYBRIDIZATION MICROARRAYS. Wang 1, D. Liu 1 and N. Schanen 2*. 1Dept Human Genetics UCLA, Los Angeles, CA 90095 and Nemours Biomedical Research, A.I. duPont Hospital for Children, Wilmington, DE 19803

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Slide Session 4: Topic 4: Descriptive

Diagnostic S4.4.1 RELIABILITY AND VALIDITY OF THE PDD BEHAVIOR INVENTORY. I.L. Cohen. NYS Institute for Basic Research in DD. Staten Island, NY 10314. S4.4.2 ARE PERSONS WITH AUTISM SPECTRUM DISORDERS AT RISK FOR THE DEVELOPMENT OF SEXUAL PROBLEMS? H. Hellemans. University of Antwerp, Belgium. S4.4.3 THE DEVELOPMENT AND APPLICATION OF THE COGNITIVE AND SOCIAL PLAY ASSESSMENT SCALE FOR USE WITH CHILDREN WITH AUTISM. A. Sorman, K. White and C. Claflin*. Northwest Missouri State University, Maryville, MO 64468. S4.4.4 SEVERE CHALLENGING BEHAVIOR IN INDIVIDUALS WITH AUTISM AND MENTAL RETARDATION: THE EFFECTS OF AN INTENSIVE CARE SYSTEM. I.A. Van Berckelaer-Onnes and Y.M. Dijkxhoorn, Leiden University. The Netherlands. S4.4.5 ANALYSIS OF SOCIAL INITIATIVE POTENTIAL AS A PIVOTAL VARIABLE IN THE PROGNOSIS FOR CHILDREN WITH AUTISM . L.A. Vismara, R.L. Koegel* and& L.K. Koegel. Autism Research & Training Center, University of California, Santa Barbara, CA 93106-9490.

Slide Session 4: Topic 5: Microbiology and

Immunology of Autism Spectrum Disorder

S4.5.1 INCREASED SPONTANEOUS TNFalpha AND DECREASED IL-10 PRODUCTION IN PERIPHERAL AND ILEAL LYMPHOCYTES IN AUTISTIC CHILDREN. P. Ashwood, A. Anthony and A.J. Wakefield*. Paediatric Gastroenterology, Royal Free Medical School, London, UK. S4.5.2 STRAIN DIFFERENCES IN ONTOGENY OF CNS DISTURBANCES FOLLOWING LATE GESTATIONAL IMMUNE CHALLENGE IN A MOUSE MODEL. M. Hornig, R. Schlaberg, D. Chian, C. Kirk, P. Hardigan and W.I. Lipkin*. Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, New York, NY 10032. S4.5.4 THE ROLE OF MATERNAL IMMUNITY IN SUSCEPTIBILITY TO VIRUS INFECTION AND DISEASE. G.F. Rall, J. Chandra, L.A. Gechman and C.E. Patterson. The Fox Chase Cancer Center, Philadelphia, PA 19111. S4.5.5 TAGMAN RT-PCR DETECTION OF MEASLES VIRUS GENOMIC RNA IN CEREBROSPINAL FLUID IN CHILDREN WITH REGRESSIVE AUTISM. O. Sheils, J.J. Bradstreet, J. El Dahr, S.M. Montgomery, A.J. Wakefield, J.J. O’Leary. Department of Histopathology ST James' Hospital Dublin Ireland S4.5.6 REDUCED IGG RESPONSE TO COMMON VACCINE ANTIGENS FOR PATIENTS WITH AUTISM SPECTRUM DISORDER. J. Van de Water*, P. Ashwood, R. Hansen, B. Goodlin-Jones, K. Lam and M.E. Gershwin. Internal Medicine and M.I.N.D. Institute, UC Davis, Davis, CA 95616

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Poster Session 1: Topic 1: Functional Brain

Imaging P1.1.1 EEG ASYMMETRY AND SUBTYPES IN AUTISM. P.C. Mundy*, C. Burnette and S.K. Sutton. Department of Psychology, University of Miami, Coral Gables, FL, 33146 The use of psychophysiological measures associated with social behavior and related processes may be especially useful for defining subgroups of autism spectrum disorders (Coleman, 1987; Dawson et al., 1995; Modahl et al., 1998). Accordingly, this study examined the hypothesis that EEG measures of anterior brain asymmetry, associated with motivation and interactive tendencies, may contribute to a better understanding of social subtypes of higher functioning children with autism. Twenty-three higher functioning children with autism (HFA, age range 8-14 years) participated in this study and were divided into three groups: Left Frontal EEG Asymmetry (LFA), Intermediate Frontal EEG Asymmetry (IFA), and Right Frontal EEG Asymmetry (RFA). Parents reported that the LFA group was significantly less socially impaired than the other subgroups and performed better on measures of cognitive flexibility. However, the LFA group also reported more social anxiety, social stress, more attributions of personal responsibility for failures (e.g., higher locus of control), as well as lower satisfaction with interpersonal relations than the other HFA subgroups. Alternatively, the IFA and RFA groups displayed more symptoms of social impairments, and less awareness of social problems. The RFA children also displayed superior performance on visual spatial measures, including WISC-III block design. These results indicated that anterior EEG asymmetry may provide an important new marker of clinically relevant individual differences and subtypes among HFA children. P1.1.2 DIFFERENCES IN BRAIN ACTIVATION IN CHILDREN WITH AUTISM INDEPENDENT OF BEHAVIORAL PERFORMANCE. S.M. Rivera*, B. Mikaelian and M.L. Henry. U.C. Davis Dept. of Psychology, Davis, CA 95616

To date, a small number of fMRI studies of persons with autism have been published, and most have used only adult subjects and tasks on which persons with autism perform poorly (e.g., emotion perception, or social cognition.) The current study adds crucial information to our knowledge of the neural pathogenesis of autism first by using fMRI with high-functioning children with autism, and second by evaluating their brain activation patterns (with respect to those of matched controls) both during a task for which persons with autism show relatively poor performance (face discrimination) and during a task for which no cognitive deficits exist (arithmetic calculation). This approach permits us to evaluate possible differences in functional neural architecture that may exist independent of performance differences. Subjects were 4 children diagnosed with high-functioning autism spectrum disorder based on DSM-IV criteria and 4 age and IQ-matched controls. Images were acquired on a 1.5T GE Advantage scanner a standard GE whole head coil and custom-built head holders, using a single-shot gradient echo, echoplanar imaging (EPI) sequence. Results show that, similar to previously reported findings with adults, children with autism show an unusual pattern of neural activation, compared to matched controls, during a face discrimination task. Critically, however, we also see a different pattern of activation on an arithmetic calculation task where no task performance differences exist between the groups. The findings are suggestive of a general disorganization of cortical networks in persons with autism. P1.1.3 DIGIT SPAN IN ADULTS WITH ASPERGER'S SYNDROME. M. Poirier, S.B. Gaigg and D.M. Bowler. Department of Psychology, City University, London EC1V 0HB, UK Although existing evidence points to unimpaired immediate memory span in individuals with autism, recent research on other aspects of memory in this group suggests that there might be subtle deficits in this domain. Bowler et al. (in press) draw a parallel between the patterns of strengths and weaknesses in memory in autism and that seen in typical ageing, especially when the latter is accompanied by frontal

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lobe impairment. Typically ageing individuals, although relatively unimpaired on memory span tasks, are impaired on more difficult serial recall tasks. If the autism-ageing parallel holds true, then span deficits should become apparent in autism when serial recall tasks are used. We asked a sample of 16 people with Asperger's syndrome and a group of matched controls to complete a span task as well as an immediate serial recall task. As predicted, the results showed an interaction between task difficulty and group: there was a marginally significant difference between groups when a span task was used, whereas the more difficult immediate serial recall task showed a clear disadvantage for the autistic group. These findings lend further support to the ageing parallel and, as the tasks used called on memory for serial order; the findings suggest a deficit in temporal encoding (Boucher, 2000) possibly due to a common underlying frontal pathology. P1.1.4 COGNITION, EMOTION, AND THE RESTING STATE: AN fMRI STUDY OF NEUROFUNCTIONAL ABNORMALITIES IN AUTISM. D.P. Kennedy, E. Redcay and E. Courchesne. Department of Neurosciences, UCSD, Department of Psychology, UCSD, Center for Autism Research, Children's Hospital, San Diego, La Jolla, CA 92037. Recent fMRI research has found several brain regions whose activity is suppressed by externally directed, cognitively demanding tasks as compared to the rest state. These regions are medial prefrontal cortex (MPFC), rostral anterior cingulate (rACC), posterior cingulate (PCC) and precuneus (Pr). By comparison, these very same regions show relatively greater activation during internally directed tasks, such as emotion processing or self/other reflection. Since autism involves impairment in these latter processes, we used fMRI to examine the responses of these brain regions during cognitive, emotional and neutral versions of the counting Stroop in autistic and normal subjects. The three versions and rest (fixation) were each presented four times in blocks, which were randomly ordered. Consistent with the literature, normals showed significant suppression in MPFC/rACC and PCC/Pr

during the cognitive Stroop, and relative MPFC activation during the emotional Stroop (p < .05, corrected). This pattern of cognitive suppression and relative emotion activation was absent in autistic patients. The results suggest that dysfunction in this important neural network may underlie deficits in emotion and self/other reflection in autism (Supported by RO1 MH36840). P1.1.5 A SPECIFIC DEFICIT OF GESTURAL IMITATION IN AUTISTIC SPECTRUM DISORDER . O. Perra, J.H.G. Williams* and A. Whiten. Child Health Dept., Univ. of Aberdeen, Aberdeen, UK, AB25 2ZD; School of Psychology, Univ. of St. Andrews, St. Andrews, UK, KY16 9JP. Autism has been associated with an imitative impairment in over 20 studies in the last 30 years. However, it is still unclear as to whether the deficit applies to all aspects of imitation or only specific domains. It is also unclear if the impairment is specific to autism, or simply a feature of co-morbid learning disability or motor coordination disorder. Our study was designed to address these two questions. An imitation battery was administered to four groups of children aged between 5-15 years. The group of children with autistic spectrum disorder all met criteria for autism on the Autism Diagnostic Interview and ASD on the Autism Diagnostic Observation Schedule. The 3 other groups were children with developmental coordination disorder, children with learning disability and normal controls. The imitation battery included a task requiring actions on an object involving hierarchical and sequential imitation, and hand action tasks. Preliminary results on 68 children will be presented. All groups performed equally well in the program-level imitation task, but children with ASD and LD had lower scores in the hand-action battery compared to typically-developing children. An analysis of these tasks revealed that while the ASD and the LD group poorly imitated simple meaningless and reversal gestures, children with ASD had specific deficits in imitation of multicomponent acts, and in imitating the force and speed of actions. These results will be discussed in terms of the perception-action mapping theory of autism.

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This study is part of a research project funded by the PPP Healthcare Medical Trust, UK. P1.1.6 UNIQUE BRAIN ACTIVATIONS TO INTEGRATION OF AUDIO-VISUAL EMOTIONAL CUES. D.L. Robins*, E.T. Hunyadi and R.T. Schultz. Yale University Child Study Center, New Haven, CT 06520 Autism is characterized by severe deficits in emotional processing. However, most research utilizes static face stimuli; these studies fall short in explaining how individuals with autism process dynamic emotions in the world. It would be helpful to have more ecologically valid stimuli, such as audio-visual movies, to elucidate the biological mechanisms underlying emotional processing. Movies were developed, portraying actors delivering sentences in four emotions (angry, fearful, happy, neutral). Seven typical individuals participated in an fMRI study in which presentation of stimuli was blocked by modality (audio-only, video-only, or audio-video) or emotion (angry, fearful, happy, neutral). Audio-video presentation was associated with significantly greater activation in the superior temporal sulcus (STS) than audio- and video-only presentation (p<2.18x10-9); STS is suggested to play a role in audio-video integration and biological motion. Emotional movies showed increased activations in amygdala and superior temporal gyrus compared to neutral stimuli. Movies were then altered such that the visual (facial expression) and auditory (prosody) emotions were incongruent. fMRI pilot data comparing perception of these mismatching movies to the original matching movies suggest common brain activations, although mismatching activation was greater. This may be due to increased perceptual difficulty of the incongruent stimuli. These paradigms may shed light on the difficulties individuals with autism encounter processing emotion during social interactions. A sample with autism is currently being recruited in order to further understand the neurobiological substrates underlying these deficits. NAAR Yale

P1.1.7 AUDITORY CHANGE DETECTION IN AUTISM : AN fMRI STUDY . M. Gomot, M. Belmonte, C. Ashwin and S. Baron-Cohen. Autism Research Centre, University of Cambridge, Department of Psychiatry, Douglas House, 18b Trumpington Road Cambridge CB2 2AH, UK. In addition to impairments in communication and social interaction, autism involves high levels of repetitive, stereotypic, ritualistic, compulsive or obsessive behavior, together with extreme resistance to change. Although this third dimension is diagnostically essential, it has received little direct research attention. We hypothesize that typical resistance to change in autism could reflect abnormal processing of unexpected stimuli. The aim of this study is therefore to identify cerebral structures involved in change detection in people with autism. Auditory frequency change detection as well as novelty detection were studied using fMRI in six 10 to 15-year-old children with autism, age- and gender-matched with six healthy children. A sequence of standard repetitive sounds (three-partial sounds: 500 Hz, 1000 Hz, 1500 Hz) was presented, in which deviant (650 Hz + 1300 Hz + 1950 Hz; p = .08) and novel sounds (p = .08) occurred infrequently. All stimuli had a duration of 80 ms and an intensity of 85dB SPL. Effect of attention on the processing of unusual stimuli was studied in two conditions, a passive and an attentive condition in which the novel stimuli are designated as the relevant task-related targets. Preliminary results are presented and may provide evidence of functional abnormalities in the processing of change and their underlying cortical networks. This could contribute to better understanding of the physiological processes underlying resistance to change in autism. P1.1.8 ATYPICAL LATERALITY PATTERNS ASSOCIATED WITH EFFICIENCY OF VISUOMOTOR LEARNING IN AUTISTIC ADULTS. C. Cauich and R.-A. Müller*. Dept. of Psychology, San Diego State University; Dept. of Cognitive Science, University of California; San Diego, CA 92120. Motor learning deficits have been reported in autism, but the brain bases of these abnormalities

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are unknown (1). Our previous fMRI studies of visuomotor coordination and learning in autism showed abnormal frontoparietal activation patterns (2,3). However, hemodynamic effects associated with efficiency of visuomotor learning have not been previously reported. We examined effects associated with performance level during motor learning. We studied 8 high-functioning autistic men and 8 gender, handedness, and age-matched control subjects during visually prompted learning of an 8-digit sequence, using fMRI. Task by performance interaction effects were determined using contrast weights based on error rates and RT in general linear tests. In the control group, low performance was associated with activation in (predominantly left) parietal cortex (areas 7,40). Autistic patients showed similar effects in right parietal cortex, but inverse effects (associated with high performance) in left parietal cortex. The control group also showed significant effects associated with high performance in right middle and superior frontal gyri (areas 6,8). This effect was absent in the autism group. Our results are consistent with previous findings of impaired frontoparietal function and atypical hemispheric asymmetries during visuomotor learning in autism (2,3). (1) Mostofsky et al., JINS (2000); (2) Müller, R-A et al., Neuroimage (suppl., 2003); (3) Müller, R-A et al., Am J Psychiatry (2003). Supported by NIDCD 1 RO1 - DC06155 P1.1.9 BOLD SIGNAL COVARIANCE SUGGESTS MOSTLY INTACT THALAMOCORTICAL FUNCTIONAL CONNECTIVITY IN AUTISM A. Mizuno, B.C. Dahl, M.E. Villalobos and R-A. Müller *. Brain Development Imaging Lab, San Diego State University, San Diego, CA 92120. Based on evidence for early cerebellar Purkinje cell loss, we previously hypothesized impaired cerebello-thalamo-cortical connectivity in autism (1). This may be supported by reduced neuronal integrity in the thalamus (2). We examined functional connectivity between thalamus and cerebral cortex, as assessed through BOLD signal covariance (cf. 3). Using fMRI, we studied 8 high-functioning autistic men and 8 handedness and age-matched controls,

who performed a visually prompted 6-digit sequence with the preferred hand. For each subject, functional connectivity was computed in terms of signal covariance with the mean time series in bilateral thalami. Both groups showed significant covariance clusters distributed across all 4 cerebral lobes, consistent with known extensive thalamocortical connectivity. Functional connectivity between thalamus and insula was significantly stronger in the autism than in the control group, with similar in bilateral pericentral cortex. Controls also showed significant functional connectivity between thalamus and frontopolar area 10, which was absent in the autism group. Our findings suggest largely functional thalamocortical connectivity in autism, with the exception of connections between thalamus and frontopolar regions. (1) Müller et al., Am J Psychiat 160:1847; (2) Friedman et al., Neurol 60:100; (3) Xiong et al. Hum Brain Mapp 8:151; Allen et al. JINS (suppl. 2003). Supported by NIDCD 1R01-DC06155 P1.1.10 BRAIN SEROTONERGIC ABNORMALITIES IN AUTISTIC CHILDREN . S. Chandana, M. Behen, R. Rothermel, C. Juhasz, O. Muzik, H.T. Chugani and D.C. Chugani. Wayne State Univ., Children’s Hosp. of Mich., Detroit, MI 48201 We previously reported abnormalities of brain serotonin synthesis in frontal cortex, thalamus and cerebellum, as well as age-related changes of whole brain serotonin synthesis in autistic children. In the present study, we measured cortical and subcortical serotonin synthesis in a large group of autistic children (M=88, F=29; age=6.5±2.7 years; range=2.0-15.3 years), using the tracer alpha[11C]methyl-L-tryptophan (AMT) with PET. Extent of cortical abnormality was objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 SD of normal asymmetry). ROI analysis was performed to determine asymmetry of medial temporal structures, thalamus, caudate, putamen and cerebellum. Sixty-four autistic children showed abnormal cortical asymmetry. Decreased cortical AMT uptake was observed on the left in 31, on the right in 29 and bilaterally in 4 children. The extent of cortical

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asymmetry could be characterized as frontal cortex only (F;n=20), frontal and temporal (FT;n=15), and frontal, temporal and parietal (FTP;n=15). Abnormal asymmetries were found in medial temporal structures (FTP; p=0.023), putamen (FT, p=0.038; FTP, p=0.052), thalamus (FT, p=0.006), and cerebellum (FT, p=0.049; FTP, p=0.005) compared to normal pediatric controls. Decreased AMT uptake in left cortex was related to less functional language. Mixed handedness was more prevalent in children with right-sided cortical decreased AMT uptake. Our data show several patterns of lateralized serotonergic abnormalities in autistic children. Furthermore, the side of abnormalities are related to behavioral characteristics. Supported by NIH HD34942,MIRA and Pheasant Ring Foundation. P1.1.11 ABNORMAL PROCESSING OF HIGH AND LOW SPATIAL FREQUENCIES IN AUTISTIC CHILDREN. M.A. Boeschoten, C. Kemner, J.L. Kenemans and H. van Engeland. Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, 3508 GA, The Netherlands. The Netherlands Organisation for Scientific Research*. Many studies, behavioral, fMRI and electrophysiological, have indicated that autistic children show abnormalities in visual perception. A striking example of this is the finding that autistic children show abnormal perception of faces. A recent study by Deruelle et al. (in press) indicated that autistic and Asperger children relied more on high spatial frequency (i.e. local) information than low spatial frequency (i.e. configural) information when processing faces. In contrast, developmentally normal children relied more on low spatial frequency information. This seems to suggest that autistic children may have an abnormal processing of high and low spatial frequencies (SF). The present study investigated whether deficits in the processing of SF existed at an early sensory level. This was done by the measurement of VEPs to low and high SF gratings in a group of autistic and developmentally normal children (matched at sex, age and IQ). The use of a multi-electrode montage enabled dipole source analyses. Results indicated that developmental normal children showed the typical

SF-related differences in VEPs and dipoles in posterior regions as reported previously for normal adults. However, autistic children did not show the same typical differences. VEPs of autistic children showed smaller differences between high and low SF. Moreover, the dipoles of the autistic group showed more similar solutions for both high and low SF. In conclusion, present data seem to indicate that already at an early sensory level the processing of SF seems to be disturbed in autism. P1.1.12 FEAR POTENTIATED STARTLE AND AUTISM. R. Bernier, G. Dawson* and H. Panagiotidas. University of Washington, Box 357920, Seattle WA, 98195. Currently, the neurobiological basis of autism is not well understood; however, autopsy, structural MRI, functional MRI, and primate studies have implicated the amygdala in the disorder. Two competing hypotheses regarding amygdale dysfunction in autism have been proposed: (1) The amygdala is under-responsive, in which case it would be predicted that, in a fear potentiated startle experiment, individuals with autism would exhibit decreased fear conditioning and/or potentiation; and (2) The amygdala is over responsive, in which case it would be predicted that individuals with autism would exhibit an exaggerated potentiation of the startle response. Fourteen adolescents and adults diagnosed with autism and fourteen age, gender, IQ, and anxiety level matched typical teens and adults participated in a fear potentiated startle paradigm to examine these competing hypotheses. Both participants with autism and typical participants potentiated the startle response following fear conditioning and no differences in the latency or amplitude of the potentiated startle response between the control and autism groups were found. This suggests that the amygdala, as tested by the fear potentiated startle paradigm, is functioning typically in individuals with autism. Furthermore, the results suggest that the heightened anxiety in social situations that is found in individuals with autism is not a core feature of the disorder, but perhaps an associated disorder resulting secondary to autism. Supported by NICHD PO1HD34565 and NIMH U54MH066399.

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P1.1.13 WHITE AND GRAY MATTER DIFFERENCES IN AUTISM USING VOXEL-BASED MORPHOMETRY. E.D. Bigler, S.L. Provencal, W. McMahon and J.E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. Structural MRI findings using traditional volumetric measurements in autism are often complicated by inconsistent control of variables such as head size and intellectual functioning. This study applied voxel-based morphometry (VBM) to segmented gray and white matter brain volumes of individuals with autism and controls. Data were analyzed using statistical parametric mapping (SPM) techniques. In the first comparison, few significant differences were found between normocephalic, high-functioning autistic subjects (n=28) and normocephalic controls (n=18). Numerous density differences were found, however, in a comparison between autistic individuals with macrocephaly (n=15) as compared to controls with benign macrocephaly (n=9). Gray and white matter differences were prominent in frontal regions, fusiform gyri, superior temporal gyri, and cerebellar hemispheres. Lastly, brain morphometry was examined in a small sample of individuals with low-functioning autism (n=5) verus high-functioning autism (n=28). Gray matter differences were found in the left temporal lobe and bilateral cerebellar hemispheres. Bilateral white matter density differences were noted in superior temporal gyrus. Overall, gray and white density differences were found in regions consistently implicated in the neurobiology of autism. Experimental control of characteristics (e.g., head size and intellectual functioning) and the use of these findings in guiding future research are discussed. Funded by NICHD 5 U19 HD035476-07, the NICHD Collaborative Programs of Excellence in Autism, and the Ira B. Fulton Foundation.

Poster Session I: Topic 2: Face Processing P1.2.1 BRAIN FUNCTION AND GAZE AVERSION IN INDIVIDUALS WITH AUTISM: EFFECTS OF FAMILIARITY . K.M. Dalton, B.M. Nacewicz, A.L. Alexander, M.A. Gernsbacher, H.H. Goldsmith and R.J. Davidson. Waisman Center, Keck Lab, Univ. of Wisconsin, Madison, WI. 53706. It is proposed that deficits in face processing in individuals with autism spectrum disorder (ASD) have their roots in differences in gaze pattern and central brain mechanisms associated with the processing of human faces and emotions. Of key interest to this study is the role of familiarity with the faces in gaze pattern and brain function in individuals with ASD versus neurotypical controls. Twenty-seven males (16 with ASD, 11 controls) participated in the study. Structural and functional (BOLD gradient echo) brain MRI images were acquired on a GE 3T scanner along with eye tracking. Participants were presented with 40 images of human faces and objects, half familiar, half unfamiliar. The ASD group fixated on the eyes of the familiar faces less than the controls, F(1,26) = 5.19, p = .03. Furthermore, greater BOLD signal was seen in the control versus ASD group in the right fusiform gyrus for the familiar faces, F(1,24) = 38.10, p = .000002. Importantly, the amount of time the individuals with ASD spent fixating on the eyes was positively correlated with activation in the right fusiform, r = .57, p = .02. These findings suggest that gaze-aversion is a fundamental characteristic of ASD that is directly related to activation in the right fusiform gyrus. Funded by STAART grant U54MH066398 awarded to H. Tager-Flusberg (PI) and R.J. Davidson and a NARSAD Distinguished Investigator Award to R.J. Davidson P1.2.2 REDUCED AFFECTIVE SALIENCE OF SOCIAL STIMULI IN AUTISM . J.L. Wilbarger, D.N. McIntosh* and P. Winkielman. Emotion and

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Cognition Lab, Department of Psychology, University of Denver, Denver, CO 80208. Affective startle modification has been used extensively to examine automatic responses to affective stimuli. Of interest in the study of autism are responses to affective social stimuli. Affective modification of startle responses of 14 high functioning adults with autistic spectrum disorders (ASD) were compared to responses of 14 typically developing individuals matched for age, gender and verbal ability. Startle magnitude was measured by recording electromyographic (EMG) activity over the orbicularis oculi during presentation of 95db startle probes while participants viewed affective pictures with and without social content. Results indicate a significant interaction between groups by affective category and social content. Typical individuals demonstrated potentiation of startle to negative images and suppression of startle to positive images for both social and nonsocial content. Further, for typical individuals social stimuli appears to enhance startle modification; producing greater potentiation of startle while viewing negative images and greater suppression of startle while viewing positive images. Individuals in the ASD group demonstrated potentiation to both positive and negative images regardless of the social content and did not demonstrate enhancement of startle modification for affective social images. Results suggest that social content does not enhance saliency of affective stimuli for individuals with ASD. (1st author now at the University of Wisconsin, Department of Kinesiology. 3rd author now at the University of California, San Diego, Department of Psychology.) P1.2.3 AUTISM SEVERITY CORRELATED WITH REDUCED BRAIN ACTIVATION DURING A FACE PROCESSING TASK. J.N. Lee, E.D. Bigler, S.L. Provencal, W. McMahon and J. E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. Social deficits are hallmark characteristics of autism. Brain structures integral to efficient

processing of human faces may play a role in social development outcomes. Functional magnetic resonance imaging (fMRI) images were acquired from high-functioning autistic (n=5) and typically developing individuals (n=5) while performing a human faces versus objects task. Brain activation patterns were then correlated with behavioral measures of face recognition skills and autistic symptomatology. Reduced activation of brain regions underlying information processing of human faces for individuals with autism compared to controls was expected. An additional hypothesis was that reduced activation in autism would be correlated with poor performance on the face recognition measure as well as increased autism severity. Consistent with past studies, reduced activation of the fusiform gyrus and amygdala was found in autism versus controls. This reduced activation was not significantly correlated with neuropsychological performance on an immediate or delayed face recognition memory task. Reduced activation of the fusiform gyrus, however, was significantly correlated with increased autistic symptom severity in language and social domains. Findings contribute to a better understanding of brain-behavior relationships underlying autism spectrum disorders. Funded by NICHD 5 U19 HD035476-07, the NICHD Collaborative Programs of Excellence in Autism, and the Ira B. Fulton Foundation. P1.2.4 GAZE AT EYES AND ADI-R . C.Y. Trepagnier*, M.M. Sebrechts, R. Ramloll, M. Coleman, A. Finkelmeyer, L. Barker, M. Paxton Jones, W. Stewart and K. Gleeson. Psychology Department, The Catholic University of America, Washington, DC 20064 In an earlier study using a head-worn stereoscopic display and eye tracker, high-functioning Autism Spectrum Disorder (ASD) participants looked less than controls at the interior of the face (Trepagnier et al., 2002). We report here preliminary results for a similar task using a table-top tracker and 2-dimensional display. Of the 8 experimental group participants whose data have been analyzed to date (1 female; age 12,4 to 22,8, all with a clinical diagnosis of Aspergers Disorder ), 6 met Autism Diagnostic Interview (ADI-R) criterion for

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ASD. Correlations for gaze duration and number of fixations on eyes with the ADI-R social subscore were -.736 and -.764, respectively, for the whole group, and -.813 and -.815 for the 6 meeting criterion for ASD (all correlations significant at p < .05). A trend in the same direction for total ADI-R score failed to reach significance. No significant between-group face gaze differences have emerged from analyses of gaze during the 4-second displays; data for initial fixations has yet to be analyzed. While we can only speculate on reasons for absence of between-group face gaze differences, the strong within-group correlation between gaze at eyes and early social behavior points to a connection between face gaze and autistic social development (Trepagnier, 1996). Partial support for this work was provided by National Institute on Disability and Rehabilitation Research grant H133E980025. P1.2.5 EXPERTISE IN THE ATTRIBUTION OF EMOTION FROM DYNAMIC FACES IN HIGH FUCTIONING INDIVIDUALS WITH SOCIAL UNDERSTANDING DIFFICULTIES . J. Piggot, A. Reiss and J. Hallmayer. Department of Psychiatry and Behavioral Sciences, University of Stanford, CA 94305. Objective: To determine how expertise in the attribution of emotion from dynamic faces relates to Social Understanding Difficulties (SUD). Method: Sixty individuals [(10-8yrs)(FSIQ-120)] with SUD as determined by a score >70 on the Social Responsiveness Scale (SRS) (Constantinos et al., 2002) and their families undertook the Dynamic Faces Task. Each individual saw 80 dynamic faces, 40 verted and 40 inverted, 40 changed from neutral to a happy expression and 40 faces to a sad expression over a 10 second period. Accuracy and reaction time were measured. Results: Expertise was defined as the combination of percentage correct answers and speed. Expertise was significantly correlated to the SRS (r = 0.3; p = 0.00) and differentiated the probands from their male and female siblings (p = 0.005 and 0.03 respectively). Accuracy was found to explain 40% (p = 0.000008) of the variance within

families, interestingly reaction time was found to be non-familial. Conclusion: This study supports that expertise in the attribution of emotion is correlated with SUD and distinguishes probands from their siblings. The study also suggests that accuracy in the attribution of emotion from dynamic faces may represent an endophenotype in the families high functioning individuals with SUD. Roland D. Ciranello Fellowship awarded to Dr. J. Piggot by the National Alliance of Autism Research. P1.2.6 FACE RECOGNITION STRATEGIES USED BY INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS. L. Kopelioff*, V.E. Stone and C.L. Reed. U of Denver and U of Queensland, Dept. of Psychology,U of Denver,Denver,CO,80208 Past research suggests that individuals with autism spectrum disorders (ASD) have a face-recognition impairment that may stem from difficulty processing configural information (i.e., distances between features on a face), and that they instead process faces by individual features. We assessed face-processing strategies in ASD using a forced-choice recognition task, comparing recognition performance in conditions in which target and probe faces differed either by configuration (features moved into or away from a central point) or by features (different eyes, nose, mouth). Performance on face trials was also compared to difficulty-matched house trials, to assess whether any recognition impairment is specific to faces or more general. Furthermore, to explore the effect of short-term memory demands, we also compared discrimination between faces that were side-by-side and recognition of faces with a short-term memory component (STM). As expected, adolescents and young adults with ASD (n=16) showed a face-specific recognition deficit compared to age- and performance IQ- matched controls (n=16) when stimuli were presented in the STM condition. No deficit was evident when stimuli were presented side-by-side. The ASD group did not exhibit a deficit in configural face processing: both groups of participants recognized both faces and houses that differed by features better than those that differed by configuration, in all presentation conditions. These

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findings suggest that face memory rather than face perception is what causes difficulties for people with ASD. Further, the face recognition impairment in ASD cannot be fully explained by a deficit in configural face processing. P1.2.7 A STUDY OF PERCEPTIVE HIERARCHIZATION OF FACES IN AUTISM. A. Lahaie, L. Mottron*, M. Arguin, C. Berthiaume, B. Jemel and D. Saumier. Perv. Dev. Disord.Spec. Clin., Riviere-des-Prairies hosp., Montreal, Qc, Can., H1E 1A4. Deficits in face processing are reported among individuals with autism (IWA), which have been suggested to account for the social difficulties observed in this population. The exact nature of the cognitive deficit subtending atypical face processing in autism is still unknown. One hypothesis is that IWA have a deficit in processing configural face information, leading them to rely on local cues alone. An alternative hypothesis is that an enhancement of local processing is actually present, without configural face processing deficit. Exp. 1 uses face inversion effect in order to assess the integrity of configural face processing in IWA. The results showed an inversion effect similar for IWA as for control participants, suggesting that configural processing of faces is intact in this disorder. In exp. 2, we used a priming paradigm that directly assessed both local and configural levels of face processing. The results showed that the priming effect obtained with 2 types of face segmentation were identical in both autistic and control groups, but there was a greater priming effect for single face parts in the autistic group. The results of this study demonstrate that the configural processing of faces is intact, but that IWA have an enhanced processing of face parts. These results are consistent with numerous studies in non-social domains showing a enhanced processing of local information in the visual and auditory domains. Thus, the face processing peculiarities observed in autism are likely not linked to socially specific mechanism, but to a generally enhanced processing of the local aspects of social and non-social information. FCAR -FRSQ & NSERC.

P1.2.8 FAMILIAR FACE RECOGNITION IN CHILDREN WITH AUTISM . R. Wilson*, O. Pascalis and M. Blades. Department of Psychology, University of Sheffield, Sheffield, Yorkshire, S10 2TP, U.K. Recognition of familiar faces is essential for effective socialization. Children with autism have however been shown to display deficits in the recognition of familiar faces (Boucher and Lewis, 1998). This study investigated the pattern of familiar face recognition displayed by children with autism, (N=17), compared to children with learning difficulties, (N=17), and typically developing controls, (N=17). Children were tested on a forced-choice familiar face recognition task with three conditions: full faces, inner face features and outer face features. Thirty photographs of staff from each group’s school (autism, learning difficulties and typically development children) were taken and used as the familiar faces. Ten faces were used in each condition (full, inner and outer) so that no face was shown twice. All three groups of children displayed the same pattern of face feature superiority; full face then inner face features then outer face features. Both the children with autism and the children with learning difficulties were slightly impaired in terms of number of faces recognized compared to the typical development group, but there was no autism specific deficit. We concluded that children with autism have more typical patterns of familiar face recognition than previous researchers have suggested. P1.2.9 AMYGDALA VOLUME AND FUNCTION DURING RECOGNITION OF EMOTIONAL FACIAL EXPRESSIONS. B.M. Nacewicz,* K.M. Dalton, A. Alexander, M. Gernsbacher, H. Goldsmith and R.J. Davidson. Waisman Center, Univ. of Wisconsin, Madison, WI. 53706. Reports of gaze aversion and exaggerated electrodermal activity in autism raise the possibility that some individuals experience exaggerated arousal to social stimuli. Past results have shown amygdala volume to predict gaze-aversion, pupil diameter, and recognition of emotional facial expressions during an fMRI task. The amygdala volume/activation relationship in autism is not well

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established. To this end, hand drawn amygdala ROIs were applied to functional data acquired while subjects distinguished emotional (happy/ angry/fearful) facial expressions from neutral ones. These data were compared to activation in putative pain/discomfort and emotion-regulation areas. Participants included 13 males with ASD (mean age 16.8y) who varied from minimally verbal to verbally fluent, and 11 typically developing control males (mean age 16.3). Functional and T1-weighted structural images were acquired on a GE 3T scanner. Participants were presented with 40 pictures of human faces; approximately half of them displayed exaggerated emotional expressions. Half each of the emotional and neutral faces were forward-facing; the other half were angled away from the viewer. Amygdala ROIs were traced in 3-dimensions and functional data were extracted using the Spamalize software package. Amygdala volume and function were compared and related to activation in ACC, OFC, and insula. Funded by STAART grant U54MH066398 awarded to H. Tager-Flusberg (PI) and R.J. Davidson and a NARSAD Distinguished Investigator Award to R.J. Davidson. P1.2.10 NEURAL MECHANISMS INVOLVED IN LEARNING FROM FACIAL EXPRESSIONS. C.I. Hooker, L.T. Germine, E. Owen, R.T. Knight and M. D’Esposito. Helen Wills Neuroscience Institute & Psychology Department, University of California, Berkeley Prior research indicates that children with autism do not use another person’s facial expression to learn about ambiguous situations as consistently as normally developing children. However, the cause of this social referencing deficit is unclear. The purpose of this study is to identify basic neural mechanisms of learning the emotional valence of novel objects through facial expressions of another person. In an event-related fMRI study, healthy adult subjects performed a visual discrimination, reversal-learning task in which they learned whether someone reacts happily or fearfully to a novel object. After an initial learning period, the stimulus-emotion association is reversed, and subjects guide subsequent responses by information gained from happy and fearful facial

expressions. Results show that facial expressions critical for learning stimulus-emotion associations evoke greater neural response in the ventral striatum, and ventrolateral and orbital prefrontal cortices than those same facial expressions presented after the stimulus-emotion association is already learned. This neural network identified for learning from facial expressions is identical to the neural network previously reported for learning from primary reward and punishment. These results provide neuroimaging evidence that, in a social learning environment, facial expressions may have primary reinforcement value for normally developing individuals. These findings are consistent with the notion that a deficiency in the natural reinforcement value of facial expressions may contribute to social referencing deficits in autism. Poster session 1: Topic 3: Early Detection,

Screening, Diagnosis and Intervention

P1.3.1 DEVELOPMENT OF VERBAL OPERANTS DURING PIVOTAL RESPONSE TRAINING . D. Rausch-Harris, S. Dufek and L. Schreibman*. University Of California, San Diego 92093-0109 The current study examines the development of Skinner’s verbal operants (as defined in his 1957 book entitled Verbal Behavior) within the framework of a specific behavioral therapy, Pivotal Response Training (PRT). PRT is a behavioral treatment for children with autism and related disorders based on the principles of applied behavior analysis. Preliminary analysis in our laboratory indicates that PRT is effective in increasing each functional unit of language (echoic, mand, tact, intraverbal, autoclitic), resulting in language that is functional for the child. Previous research in the efficacy of PRT indicates that there exist specific child profiles that can predict how well a child will respond to this treatment (Scherer and Schreibman, in press). Identification of the development of each functional unit of language (e.g. Skinner’s verbal operants) throughout a course of PRT has not previously been researched. Children participating in this study are

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between the ages of 2 and 4, have a diagnosis of autism, have less than 10 functional words, and have not received PRT in the past. Children will receive 10 hours of PRT per week over a period of 3-6 months. The current study aims to identify the specific child characteristics that impact the development of each of the verbal operants. More specifically, this study is looking at the relationship between the development of each verbal operant and the child’s behavioral profile. Such information will provide theoretical as well as practical value in further explaining language development, predicting success with specific treatment methodologies, and better individualizing treatment to match the child’s unique profile. P1.3.2 PREDICTION TO ONE YEAR FOLLOW-UP FROM TARGETED JOINT ATTENTION AND PLAY INTERVENTIONS. C. Kasari, S.F. Freeman and T. Paparella. University of California, Los Angeles*, LA, California, 90024. This study reports on distal outcome measures from a controlled intervention to increase skills considered core deficits in autism - joint attention and play. Research has shown that children with autism who evidence greater skill in joint attention and symbolic play have better language abilities (Mundy et al., 1986; Kasari, Sigman, Mundy, & Yirmiya, 1990) and that joint attention predicts to language in later years (Mundy, Sigman, & Kasari, 1994; Sigman & Ruskin, 1999). In our study, children with autism from a Partial Hospital Program were randomized to treatment conditions of joint attention (n=20), symbolic play (n =21) or control (n=17). The intervention groups received a daily 30 minute individual intervention for an average of 6.5 weeks. Pre and post treatment, and 12-month follow-up assessments included the Mullen Developmental Scales, Reynell Language Scales, Early Social Communication Scales, Structured Play Scales and a parent-child interaction (MCX). Targeted intervention variables were examined on the non-standardized exit assessments as they predicted to 12-month expressive language. Responsive joint attention skills (ESCS), child initiated joint attention states (MCX), play level

(Structured Play) and symbolic play (MCX) at exit all significantly predicted expressive language at 12 months (p < .001). Thus both joint attention and play skills predicted to language 1-year post treatment. Further analyses on related variables, mental age, receptive language, and IQ will be examined. P1.3.3 DIFFERENTIATING BETWEEN AUTISM SPECTRUM DISORDERS AND OTHER DEVELOPMENTAL DISABILITIES USING THE MODIFIED CHECKLIST FOR AUTISM IN TODDLERS (M-CHAT). P. Dixon, J. Kleinman, J. Pandey, L. Wilson, H. Boorstein, E. Esser, S. Lanz, M. Barton, S. Allen, J. Green, T. Dumont-Mathieu, G. Marshia, D. Robins and D. Fein*. University of Connecticut Psychology Department, Storrs, CT 06269 Early detection of Autism Spectrum Disorders (ASD) is crucial for optimal prognosis. The M-CHAT (Robins, Fein, Barton & Green, 2001) is a parent-report checklist designed to detect ASD in 16-30 month old children. To date, 2,528 children have been screened. Those who failed the screening and a telephone follow-up (n= 147, mean age= 26 months) were evaluated; 106 were diagnosed with ASD and 32 with language or global developmental delay. The other 9 children were eliminated from the analyses because of a unique diagnosis (e.g., ODD, ADHD). Robins et al presented screening items that differentiated the ASD children from the total screened non-autistic population, most of whom were typically developing. The sample of non-autistic evaluated children is now large enough to compare to the ASD children. Percent failure rates will be presented for each diagnostic group for each of the 23 M-CHAT items. Significantly more of the children diagnosed with ASD failed items: pointing to request, p <.05, pointing to show interest, p <.001, taking an interest in other children, p <.05, responding to name, p <.02, understanding what people say, p <.05, appearing deaf, p < .003, and unusual finger movements, p <.05. These items largely overlap with the items identified as most critical in distinguishing ASD from normal development. Therefore, these items can differentiate ASD children, not only from normally

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developing children, but also from children with other early manifesting developmental disabilities. P1.3.4 SCREENING FOR AUTISM IN PEDIATRIC PRIMARY CARE: RESULTS OF A PILOT STUDY. J.A. Pinto-Martin*, M. Souders, S. Wightman-Hertz, E. Giarelli, S. Levy and PA-CADDRE. Univ.of Penn., Phila., PA 19104 The last ten years have seen considerable improvement in standardized screening techniques for autism spectrum disorder (ASD). The Pennsylvania Center for Autism and Developmental Disabilities Research and Epidemiology (PA-CADDRE) is piloting a study to assess the feasibility of early identification of ASD, using trained research nurses to conduct developmental screening at the 18 and 24 month well-child pediatric visit. The screening protocol includes two instruments, the Checklist for Autism in Toddlers (CHAT), a 5 item, clinician-administered behavioral rating scale, and the Modified-CHAT, a 23 item, self-administered questionnaire to parents about a child’s current abilities. Parents complete the questionnaire while in the waiting area. The CHAT observations are easily completed by the nurse while weighing and measuring the child. Of 41 toddlers scheduled for a 18-24 month check-up during screening hours to date, there were 16 no shows, 8 parents refused and 17 consented to participate. Children ranged in age from 18-26 months (M =21.6 mos). Three of the 17 children screened positive on one or both screening measures. Challenges identified thus far include high no-show rates, the complicated consent process, and the fact that the psychosocial stressors and low level of education of this inner-city population results in less awareness of developmental issues. The rationale and opportunities for including medical support personnel in an enhanced developmental screening capacity will be presented. P1.3.5 DEVELOPMENT OF AUTISTIC TRAITS IN YOUNG INFANTS (0-4 YEARS OF AGE) WITH AUTISM AND OTHER SOCIAL DEVELOPMENTAL DISORDERS. F. Naber, S.H.N. Willemsen-Swinkels, E. van Daalen, J.K. Buitelaar, H. van Engeland.

Department of Child and Adolescent Psychiatry, University Medical Center Utrecht-The Netherlands, P.O. Box 85500 3508 GA Utrecht. Subjects who received the diagnosis of autism show deficits on three area's; social development, language development and stereotypy. It was assumed that children with autism already show these deficits in the first years of life, before they received a diagnosis. Due to difficulties to diagnose under the age of three, little was known about the development of these children in the first years of life although these years are very important for the social- and language development. To study the children with autism at this age, might give more insight in the development of these disorders. In our study we screened children at the age of 14 months with social developmental disorders. The children who were found to be at risk for social developmental disorders were followed in their development up until the age of 4 years. At this age they received a diagnosis. Studying the behavior that these children showed at a younger age, might give some information about the development of children with social developmental disorders. All three area's of the DSM-IV criteria for autism were analyzed at this young age. P1.3.6 EARLY REGRESSION IN SOCIAL COMMUNICATION IN AUTISTIC SPECTRUM DISORDERS. R. Luyster, J. Richler, S. Risi, W. Hsu, C. Lord* and Collaborative Programs for Excellence in Autism (CPEA). University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109. A multi-site study of 358 children with Autistic Spectrum Disorders, 21 children with developmental delays and 17 children with typical development used caregiver interviews (i.e., the Autism Diagnostic Interview - Revised) at the time of entry into other research projects and follow-up telephone interviews designed for this project to describe the children’s early acquisition and loss of social-communication milestones. Children who had used words spontaneously and meaningfully, and then stopped talking, were described by their caregivers as showing more gestures, greater participation in

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social games and better receptive language before the loss and fewer of these skills after the loss, than other children with Autistic Spectrum Disorders. A significant minority of children with autism without word loss showed a very similar pattern of loss of social-communication skills, a pattern not observed in the children with developmental delays or typical development. The current study’s source of funding was the Collaborative Programs for Excellence in Autism (CPEA), supported by the National Institute of Child Health and Human Development (NICHD) and the National Institute for Deafness and Communication Disorders (NIDCD). P1.3.7 A POPULATION BASED STUDY ON EARLY DETECTION OF AUTISM SPECTRUM DISORDERS. S. Schjolberg. University of Oslo, Institute of Psychology, Oslo, Norway. Autism spectrum disorders (ASD) are rarely diagnosed before 36 months. Deficits in use of gestures and lack of gaze monitoring are considered early signs of ASD. The study focused on identifying children younger than 36 months with delayed non-verbal skills, hypothesizing high risk of being within the ASD. Professionals at well-baby clinics (WBC) were asked to refer all children younger than 30 months causing their concern about delayed non-verbal behaviour. The scores on a 10-item checklist (the Non-Verbal Communication-Checklist; NVC-checklist) were used as a basis for referrals. The referred group comprised of 41 children born in 98/99, 30 boys and 11 girls, mean age 27.0 months (sd 6.2). Eighty two percent (N=34) received a diagnosis within the autistic spectrum. Their average NVC total score was 9.88 (sd 4.01). Two independent raters agreed in the diagnosis in 88 % of all the cases (Kappa=0.83). In order to obtain information about normal development and individual differences in the early use of non-verbal communication, all parents of children aged 12 to 36 months were asked during a four months period to fill out the NVC at their regular visit to the WBC. The total WBC screened group were 1247, mean age 18.8 months (sd 6.2). Their scores on the NVC-checklist showed a clear age trend, from < 12-month-olds scoring an average of 3.34 (sd 2.87) to

36 months olds scoring 0.29 (0.61). Test-retest reliability was 0.85. Children with ASD were identified from the general population at a prevalence rate of 29/10.000. The fact that many of the referred children had not been assessed by any developmental specialist prior to filling out the checklist indicates that it may in fact contribute to earlier identification. Poster Session 1: Topic 4: Language and

Communication P1.4.1 SPONTANEOUS VOCALIZATIONS IN TWO NON-VERBAL CHILDREN WITH AUTISM . M. Boner and B. Gordon. Cognitive Neurology/ Neuropsychology, Johns Hopkins Medical Institutions, Baltimore, MD 21231. Most low-functioning individuals with autism never develop functional speech. Oromotor deficits may be one limiting factor, since many of these children demonstrate communicative intent, pragmatic, and conceptual abilities sufficient for communication via other modalities. Few studies have tried to determine which speech sounds such individuals can and can not produce. We analyzed videotape recordings of two low-functioning subjects with autism. While most vocalizations initially sounded like random squeals and fussing, a detailed evaluation by two speech pathologists independently revealed multiple consonants (/m,n,j,d,h,k,b,w,g,l/) and vowels. Following distinctive feature analysis and comparison by primary muscle use in their production, a pattern emerged. Both produced all sonorants (except /r/), used many obstruents, and omitted continuants. Both produced bilabials and velars. Nearly all of their phonemes required maximum or minimum oral cavity opening. Both produced phonemes requiring use of the primary jaw depressors (anterior belly of the digastric, mylohyoid, geniohyoid, and lateral pterygoid). Neither produced phonemes requiring the primary jaw elevators (temporalis, masseter, and medial pterygoid). These findings suggest that specific patterns of vocalization may be found in other non-verbal children with autism and that the sounds produced may be a

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viable substrate for building oral speech. Furthermore, this pattern of motor function suggests a relatively specific pattern of neuroanatomic involvement in the brainstem in such individuals with autism. P1.4.2 PRAGMATIC RATING SCALES AND ASPERGER SYNDROME: TOWARDS A MATHMATICAL MODEL. J. Harpur, M. Lawlor, K. Ashton and M. Deunk. Health Research Board.* Computer Science, NUIM, Maynooth, Ireland. Child and Family Centre, Drogheda. Trinity College. Department of Psychiatry, Dublin. The objectives are to (a) study the pragmatics rating scale (PRS) of (Landa et al., 1992) as an assessment instrument, (b) develop a revised version for use in Asperger syndrome (AS), and (c) examine a mathematical reformulation of the PRS in terms of Affect Control Theory (ACT). A group of 20 AS and 30 typical adolescents were interviewed about the verbal, nonverbal and emotional features of characters in a series of social scenario videos. Applying the PRS to the interviews revealed difficulties within the PRS. The granularity with which it operates is too coarse and the 3 subscales are too broad. A more precise mathematical analysis of the results, based on a frequency analysis in a concordance of responses, suggested the use of a theory that could predict affect within certain parameters, such as Affect Control Theory (Heise, 1987) could inject predictive rigour into the PRS. A modified version of the PRS is being trialled at present. We present a theory combining ACT with a modified PRS which will lead to a valid tool for assessing pragmatic deficiencies in Asperger syndrome. Heise, D. 1987. Affect Control Theory: Concepts and model. Journal of Mathematical Sociology 13:1-33. Landa, R, Piven, J, Wzorek, M W, Gayle, J O, Chase, G A, and Folstein, S E. 1992. Social language use in parents of autistic individuals. Psychological Medicine 22:245-254. P1.4.3 IDENTIFYING INDICATORS FOR AUTISM RISK: DEVELOPMENTAL TRAJECTORIES IN JOINT ATTENTION. A. Mastergeorge, M.

Lombardo, E. Amini and M. Awad. Early Development and Interaction Laboratory, M.I.N.D. Institute, UC Davis, UCDMC, Sacramento, California 95817 The development of joint attention in early communication has become a hallmark of reciprocity in communicative interactions. Research has documented infants’ use of nonverbal communication such as eye gaze, gestures, and vocalizations to maintain and sustain parent-infant interactions (Mundy & Gomes, 1998; Crais & Calculator, 1998; Warren & Yoder, 1998; Warren, Yoder, & Leew, 2002). For children at risk, a common initial symptom recognized by parents is delayed or abnormal language development; however, there is empirical support that suggests that social delays-including joint attention-typically appear first, and subsequently lead to the autism diagnosis. This longitudinal project is designed as a prospective investigation of children at high risk for autism-those who already have one or more siblings diagnosed with autism. Pilot data of thirty infant siblings with autism between the ages of 6 and 12 months are being collected and will be analyzed to examine specific domains in joint attention using the Early Social Communication Scales (Mundy, Hogan & Doehring, 1996). Additional qualitative analyses of eye gaze, gestures, and affect in specific joint attention activities will be examined. Since joint attention is a hallmark of early social communication and an indicator of a deficit in children with autism, the results of this paper purport to illuminate our understanding of the developmental trajectories of joint attention and social communication in infants at risk for developing autism. P1.4.4 TRAINING ORAL SPEECH IN NON-VERBAL AUTISM: A CASE STUDY. J. O’Grady, J. Juska, O. Pullara, L. Bejoian and B. Gordon. Johns Hopkins Medical Institutions, Baltimore, MD 21287. Although between one-third and one-half of all individuals with autism never develop usable oral speech, there have been few studies of why this impairment is so intractable and what approaches might be effective against it. Furthermore, what data has been reported has been inconclusive. We

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studied whether it was possible to establish oral speech in a non-verbal teenager with autism, and tried to identify successful methods. The subject was 13 years old at the start of the study. He was in a full-time home-based educational program, with 1:1 teaching. The basic goals were (a) to teach the subject to make vocalizations voluntarily, for communicative purposes, then (b) to use consonants and vowels already in the individual’s repertoire for specific communicative needs. Therefore, the basic methods used were (1) assessment of stereotypic vocalizations, (2) modeling and reinforcement of successive approximations of the targeted speech sound, and (3) maintenance of reliably produced speech sounds. Training was done during both scheduled classroom instruction and outside activities. Results: In 19 months, the subject learned the reliable use and imitation of the consonants /p, f, s, t, ¸/ for communication. In the latter part of this period, he began production of the voiced vowels /æ, ai, hæ, ?, [, I/. Results suggest that the intervention led to the establishment of oral speech in an older learner. Funding: This investigation was supported in part by an anonymous donor, The Therapeutic Cognitive Neuroscience Professorship endowment, and by The Benjamin A. Miller Family Endowment for Aging, Alzheimer’s Disease and Autism. P1.4.5 VOWELS AND CONSONANTS ARE PROCESSED DIFFERENTLY IN CHILDREN WITH AUTISM: AN ERP STUDY. E.W. Pang*, M.D. Bomba, W.J. Logan and W. Roberts. Division of Neurology, Hospital for Sick Children, Toronto, Canada, M5G 1X8. The ability to make fine auditory discriminations, especially of speech sounds, is critical to attaining language fluency and proficiency. Children with autism often demonstrate difficulties with the processing of incoming auditory stimuli; however, the brain mechanisms underlying this deficit are unknown. Event-related potentials (ERP) are brain responses measured off the scalp and can provide information about neural function and mechanisms. In particular, the mismatch negativity (MMN) is an ERP that reflects the brain’s automatic processing of fine auditory discriminations. It has been reported

that the MMN in children with autism showed a cerebral reactivity and hypersensitivity to acoustic changes when presented with tones (Gomot et al., 2002). We were interested in the MMN response to speech sounds in children with autism. We tested 15 children with autism and 15 age-matched controls (aged 6-8 yrs). They listened to three sets of stimuli: vowels (/a/ vs. /u/) and two different sets of consonant-vowel syllables (/ba/ vs. /ga/, and, /da/ vs. /ta/), while their MMNs were recorded from a whole-head electrode montage. To all stimuli, the latency of the MMN was longer in the autistic group than the controls (p<.05). Interestingly, the lag is largest with the vowel stimuli. This is counterintuitive since vowels are the easiest sounds to process acoustically. Linguistically however, vowels carry the most information and are the vehicles for conveying emotion and intonation. This difficulty in vowel processing may be indicative of the autistic’s inability to discriminate the subtleties of language. Supported by the Cure Autism Now Foundation. P1.4.6 TEXT CHAT AS A TOOL FOR REFERENTIAL QUESTIONING IN ASPERGER SYNDROME. G. Rajendran* and P. Mitchell. Sch. of Psy., Univ. of Notts. UK. Referential communication in individuals with Asperger syndrome (AS) was compared between text chat and telephone, using a route solving task. Individuals with AS were equally competent in solving the task in both media, but were less efficient than the typically developing comparison group. The strategies used by AS individuals correlated with their executive ability: Those with higher executive ability were similar to the comparison group, using the landmarks on the map to deduce the route taken. The results also demonstrated that individuals with AS, with good executive ability, were able to generate spontaneous questions in order to efficiently communicate in both media, and use that knowledge to solve a problem. In contrast, AS participants with lower executive ability used a less than ideal left/right strategies. This resulted in a slower process with more mistakes, and requiring more conversational turns. This suggests that individuals with AS who have problems of executive

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functioning also have problems communicating with others in order to solve a problem. This study was completed while the first author held an *Economic and Social Research Council PhD studentship at The University of Nottingham. P1.4.7 SOCIAL AND COMMUNICATION ABILITIES AND DISABILITIES IN HIGHER FUNCTIONING AUTISM, ASPERGER SYNDROME, AND PDD-NOS: THE VINELAND AND THE ADOS . C.A. Saulnier, A. Klin, S.S. Sparrow, D.V. Cicchetti and F.R. Volkmar. Yale Child Study Center, Yale University School of Medicine, New Haven, CT 06520. The relationship between social and communicative ability and disability as measured by the Vineland Adaptive Behavior Scales and the Autism Diagnostic Observation Schedule is investigated in relation to age, IQ, and diagnostic classification. Participants included 84 males with Autism Spectrum Disorders with a mean age of 12.4 years and Verbal IQ > 70. No significant correlations were found between ADOS and Vineland domains across diagnostic groups, and between age and ADOS scores suggesting that autism symptomatology remains stable with age. Negative relationships were found between age and Vineland scores indicating that as they grow older, individuals become less able to adaptively apply their communication and socialization skills at a rate consistent with their chronological growth (r = -.45 and -.63, respectively, p < .01). In autism, IQ scores increased with Vineland Communication scores (VIQ r = .51, p < .01; PIQ r = .50, p < .01; FSIQ r = .43, p < .05, respectively), suggesting that general cognitive ability aids in communication functioning. Furthermore, Performance IQ and Vineland Socialization scores were related, suggesting that nonverbal skills in autism aid in adaptive social functioning (r = .41, p < .01). In Asperger’s, Verbal IQ and Vineland Communication scores were related (r = .47, p < .01), suggesting that verbal skills aid in communication functioning for this group. No significant relationships were found between IQ and ADOS or Vineland scores for the PDD-NOS group. Implications for treatment are discussed. NICHD grant 5-P01-HD03008

P1.4.8 A CPEA STUDY OF LANGUAGE HISTORY AND LANGUAGE OUTCOMES IN AUTISM SPECTRUM DISORDERS. H. Tager-Flusberg*, L. McGrath, E.H. Cook, G. Dawson, M. Dunn, S. Hyman, C. Lord, P. Rodier, W. McMahon, N. Minshew, M. Sigman, A. Spence, D. Williams and F.R. Volkmar. *Lab of Developmental Cognitive Neuroscience, Boston University School of Medicine., Boston, MA, 02118-2526. This study investigated the relationship between early history of language milestones and current language functioning in a large well-defined sample of 881 children and adolescents meeting objective criteria for autism, Asperger syndrome (AS) or pervasive developmental disorder-not otherwise specified (PDD-NOS). Developmental history measures were taken from the ADI-R, and language outcomes measures included the Peabody Picture Vocabulary Test and the Clinical Evaluation of Language Fundamentals. Few of the participants (about 1%) met strict inclusionary and exclusionary criteria for the diagnosis of AS. Although as a group the participants with AS had better language outcomes, there was a substantial number of children with autism or PDD-NOS who, like the participants with AS, had normal onset of words and phrases and whose standard scores on the language tests were in the normal or above normal range. Children with autism whose language milestones were not delayed had significantly higher language test scores, independent of IQ. Discussion of these findings focuses on problems with current diagnostic criteria for AS, and the implications for considering ASD as a continuum of overlapping disorders. Funded by Grants from NIH/NICHD and NIDCD to the Collaborative Programs of Excellence in Autism P1.4.9 EARLY PREDICTORS OF LANGUAGE GROWTH IN YOUNG CHILDREN WITH AUTISM: JOINT ATTENTION, IMITATION, AND TOY PLAY . K. Toth, G. Dawson*, A. Meltzoff and J. Munson. University of Washington, Seattle, WA 98195. One of the strongest predictors of positive outcomes for children with autism is the acquisition of language. Understanding factors that predict

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language acquisition would shed light on the neural basis of autism and be useful in designing individualized interventions. In the present study, we examined the predictive relations between joint attention, imitation, and play at age 3-4 years and rate of language growth in children with autism from 3-8 years. Participants were 65 children with autism (initial mean CA = 43.6). Early Social Communication Scales (Seibert & Hogan, 1982) measured initiating and responding to joint attention. Meltzoff’s (1988) motor imitation task assessed immediate and deferred imitation, and functional and symbolic toy play were also assessed. Outcome measures included Mullen Scales language scores and Vineland Communication age equivalents obtained every 6 months to final follow-up at age 5½ -7 years. Regression analyses indicated concurrent associations between initiating joint attention and immediate imitation, and language ability. HLM growth curve analyses indicated relations between immediate and deferred imitation and toy play, and concurrent language ability at 4 years. Additionally, toy play predicted rate of language growth over time. These results suggest joint attention, imitation, and toy play all are important targets for early intervention as they may provide a foundation for later language acquisition. Supported by NICHD U19HD35465 and NIMH U54MH066399. P1.4.10 MAKING SENSE OF A CONVERSATION: NEURAL CORRELATES OF SYNTAX, SEMANTICS, AND DISCOURSE MONITORING IN CHILDREN WITH AUTISM. A.T. Wang, M. Dapretto, R. Caplan and M. Sigman. UCLA, Los Angeles, CA 90024 A disparity between formal linguistic skills (e.g., phonology, syntax) and sociopragmatic impairments (e.g., conversational discourse) is evident in high-functioning individuals with autism spectrum disorders (ASD). The goal of this study was to examine the neural representation of these relative strengths and weaknesses in the brain. Eight children with ASD and eight typically developing (TD) children listened to pairs of sentences and made judgments about sentence meaning or

discourse coherence while undergoing fMRI. In the sentence judgment paradigm, we manipulated the type of linguistic information (syntax vs. semantics) subjects had to rely on to decide whether sentences meant the same thing. In the discourse coherence paradigm, conditions varied on whether an assessment of reasoning or topic maintenance was necessary to decide if an answer made sense. No behavioral differences were observed between groups. Although both groups recruited canonical language areas in all tasks, TD children appeared to show greater activity than ASD children in the cerebellum during the syntax condition, Wernicke’s area in the semantic condition, and Broca’s area and the anterior cingulate during both tasks. For the discourse coherence paradigm, the ASD group showed less distinct lateralization profiles in response to the demands of reasoning vs. topic maintenance than the TD group. Region of interest analyses were conducted to assess the reliability of the observed differences. Preliminary results suggest that children with ASD in part recruit different neural networks than TD children during both basic-level sentence processing and more complex functions such as discourse monitoring. P1.4.11 VARIABLE PRESENTATION OF COMPLEX LANGUAGE SKILLS IN HIGH-FUNCTIONING CHILDREN AND ADOLESCENTS WITH AUTISM. D.L. Williams and N. Minshew. University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. This study examined the language skills of stringently diagnosed, verbal children with autism to determine if problems with complex language were present and the extent to which these problems were characteristic of individual members of the autism group. A second purpose was to further investigate the relationship of early history of language delay to later language functioning. Forty-five high-functioning (Verbal IQs of 85 or above) older children and adolescents with autism were compared to 45 age and cognitive-matched controls on a standardized test of ambiguous, metaphoric, inferential and figurative language. As a group, the children with autism performed significantly poorer than the controls. However, poor language

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performance was not universal in this group as a majority of the children with autism received scores that were in the average range. Present language functioning was not associated with early history of language development nor with Verbal-Performance IQ profile. This study provides support for the idea that a minority of individuals with autism has language problems beyond those sufficient to receive a diagnosis of autism. These language problems are important to recognize when developing intervention programs. Information regarding current language functioning is also important with respect to genetic studies and the interpretation of the results of neuroimaging studies. This research was supported by NICHD Grant HD35469, NINDS Grant NS33355, and by an NICHD Collaborative Program of Excellence in Autism (CPEA). P1.4.12 CONVERSATIONAL BREAKDOWN AND REPAIR IN SPEAKERS WITH AUTISM SPECTRUM DISORDER. J. Volden*, Speech Pathology and Audiology, University of Alberta, Edmonton, Alberta, Canada, T6G 2G4. Previous studies showed that speakers with autism spectrum disorder (ASD) recognized communicative breakdown and attempted repairs using a wide variety of strategies. No previous work has assessed repair abilities of these children when faced with a persistent communicative breakdown. Nine school-aged, high-functioning children with ASD were matched to nine control group children on the basis of language level. During conversation, an unfamiliar examiner engineered ten episodes of communicative breakdown. Each episode consisted of a stacked series of three requests for clarification (RQCLs) (“What?”, “I don’t understand”, “Tell me another way”). Verbal and nonverbal responses to each RQCL were coded. Reponses were analyzed by a series of repeated measures ANOVAs with diagnostic group and RQCL type/position as independent variables and type of repair as the dependent variable. Children with ASD were similar to language-matched control children in responding to RQCLs and employing a variety of repair strategies. Also, like their language-matched controls, they varied their repair strategy by adding

more and more information as the breakdown persisted. These results suggest that they were able to adopt their listener’s perspective and adjust their communication in light of previous interchanges in the conversation. On the other hand, speakers with ASD were significantly more likely than language-matched controls to respond to a RQCL with a response that was inappropriate. Funding Source: Social Sciences and Humanities Research Council of Canada, Junior Faculty Award Poster Session 1: Topic 5: Psychopharmacology P1.5.1 EFFICACY AND TOLERABILITY OF METHYLPHENIDATE IN CHILDREN WITH PERVASIVE DEVELOPMENTAL DISORDERS. A. Di Martino and A. Zuddas. Child Psychiatry, Dept of Neuroscience, Cagliari University, Cagliari, Italy This pilot study investigates the effects of chronic methylphenidate (MPH) on both ADHD-related and autistic symptoms in Pervasive Developmental Disorders (PDD), after an acute test dose administered in the clinic. 13 subjects (12 males, mean age 7.9y) with DSM-IV PDD and moderate-to-severe hyperactivity & impulsivity measured participated. Parental informed consent was obtained. One hour after the single MPH-dose (0.4mg/Kg), five subjects exhibited increased hyperactivity, stereotypies, dysphoria, or motor tics were rated “worse” on the CGI-Global Improvement Scale and not received further MPH-treatment. The remaining 8 subjects tolerated MPH and proceeded to a 12-week open trial. Severity of symptoms assessment was based on CGI, Childhood Autism, Conners Parent and Teacher Rating Scales. Scores at baseline, 1, and 3 months of treatment were compared with intent-to-treat analyses In group analysis, behavioral measures of hyperactivity, fidgetiness, and impulsivity improved significantly. Autism core symptom measures were unaffected. No significant side effects were observed in any of the 8 subjects. These results suggest that, in a subgroup of subjects with PDD, chronic MPH-therapy can be tolerated and clinically useful to improve hyperactivity and impulsivity and inattention. A single MPH test dose may be a rapid and

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relatively safe method to improve the likelihood of recognizing subjects with PDD who can benefit from chronic MPH. P1.5.2 PHARMACOLOGICAL MODULATION OF EMOTION MEMORY IN AUTISM SPECTRUM DISORDERS. A. Hillier, J.S. Chu, R.F. Miller, J. Kitzmiller and D.Q. Beversdorf. The Ohio State University, Columbus, OH 43210. Impairment in memory for emotional material among those with autism spectrum disorders (ASD) has previously been demonstrated. Among individuals without neurological disorders research has shown that pharmacological interventions can significantly impact memory for emotional material. The purpose of this study was to investigate whether pharmacological modulation would differentially affect memory for emotional material among those with ASD as compared to controls. Adults with ASD were matched in age and IQ to individuals without neurological disorders. Participants attended three testing sessions approximately one week apart. During one session they received propranolol (40mg) as a noradrenergic antagonist. On another they received ephedrine (25mg) as an adrenergic agonist, and on another they received placebo for comparative purposes. During each visit participants were presented with slides taken from the International Affective Picture System (IAPS) depicting stimuli designed to evoke negative and neutral emotional responses. A week later memory for the picture stimuli was tested. Drug conditions and order of presentation of picture types were counterbalanced. Results showed that control participants showed the typical bias for remembering significantly more negative than neutral stimuli on both propranolol and placebo, whereas those with ASD remembered negative and neutral stimuli equally. However, they did show a trend for remembering more negative than neutral stimuli when on ephedrine, a pattern not exhibited by the controls. In conclusion, this study demonstrates that pharmacological modulation can elicit an atypical pattern of emotion memory in ASD.

P1.5.3 AN OPEN TRIAL OF GALANTAMINE IN CHILDREN AND ADOLESCENTS WITH AUTISM. R. Nicolson and J. Smith. The University of Western Ontario, London, Ontario, Canada. Objective: Post-mortem studies have suggested abnormalities of the cholinergic system and a reduction in nicotinic receptor binding in autism. The purpose of this study was to assess the effects of galantamine, a cholinesterase inhibitor and allosteric nicotinic receptor modulator, in children with autism. Methods: Ten medication-free children and adolescents (eight males, two females; mean age: 9.1±3.9 years), participated in a 12-week, open label trial of galantamine. Galantamine was titrated to a maximum dose of 24mg daily. Patients were rated monthly by parents on the Aberrant Behaviour Checklist (ABC) and the Conners’ Parent Rating Scale, and by the investigator using the Children’s Psychiatric Rating Scale. Results: Six subjects were rated as significantly improved while taking galantamine. Although there were no significant differences noted on the ABC, parents rated their children as having less emotional lability and less oppositionality on the Conners Parent Rating Scale. There were also trends for reductions in hyperactivity and inattention. There was a significant reduction in the Anger subscale of the Children’s Psychiatric Rating Scale. All of the patients who were rated as significantly improved had aggression and temper outbursts as a target symptom, while only one of the non-responders had these symptoms as targets. Overall, galantamine was well-tolerated and there were no significant changes in EKG parameters or weight during the trial. Conclusions: In this open label trial, galantamine was well-tolerated and appeared to be beneficial for the treatment of agitation and aggressive behaviour in children and adolescents with autism. P1.5.4 SERUM FERRITIN AND RESPONSE TO IRON SUPPLEMENTATION IN AUTISM . W. Roberts*, C. Dosman, I. Drmic, M. Harford, W. Sharieff, R. Smith, H. Moldofsky, S. Zlotkin and J. Brian. Hospital for Sick Children/University of Toronto & Centre for Sleep and Chronobiology Disorders, Toronto, ON, Canada.

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Effects of iron deficiency have not been reported in children with Autism Spectrum Disorders (ASD). Objectives: (1) describe serum ferritin (fer) levels, (2) assess relation between serum fer and dietary intake, and (3) collect pilot data regarding response to brief iron supplementation. 33 children (mean age 6-3, 35M, 8F) completed an 8-week open label trial of oral iron suspension or microencapsulated ferrous fumarate sprinkles. Dietary intake, compliance and side effects were tracked, and fer measured at baseline and after treatment. At baseline (n=43), 76% had fer <22 ug/L (27% <12 ug/L). At the end treatment, 33% were <22 ug/L (18% <12 ug/L). More preschoolers had baseline fer <12 ug/L (9/20 vs. 3/23). 60% had insufficient dietary iron intake, more of whom were preschoolers. Geometric mean fer was 15.6 ug/L at baseline vs. 24 ug/L after treatment (p<.00001). In 6/16 preschoolers fer remained <12ug/L. No association was found between low fer and autistic symptomatology. Low serum fer is more common in ASD than the general population (range: 3%-9% in 1-11 yr. olds). Signs of iron-deficient erythropoeisis were common, representing an advanced stage of iron deficiency. Although mean fer increased overall with iron supplementation, iron stores of a minority of children (all preschoolers) remained <12ug/L following treatment. P1.5.5 PSYCHOTROPIC MEDICATION AND BEHAVIORAL THERAPY USE IN CHILDREN WITH AUTISM. K.C. Thomas, J.P. Morrissey* and A. Brewster. Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3386. This presentation brings a services research perspective to the study of medication use by children with autism. There is recent evidence about the prevalence of psychotropic medication use among children with autism, but little evidence to date describing psychotropic medication use in conjunction with other behavioral therapies. This background information is necessary in order to begin the work of distinguishing which children can benefit from the various psychopharmacological therapies and under which conditions. This study is based on a survey of approximately 300 families in

North Carolina with a child, 8 years old or younger, with autism. This presentation describes service use, payers, family stress and coping and satisfaction and concerns with care. In particular, this presentation describes variety and frequency of psychotropic medication use, reason for use, and satisfaction with this approach. Logit regressions describe child and family characteristics most often associated with psychotropic medication use, and those associated with family satisfaction with psychotropic medication use. Findings will also be presented about the relationships between use of psychopharmacological approaches, philosophical approaches to the care and treatment of autism, and behavioral therapies. Profiles of families who find pharmacological therapy useful and not useful will be highlighted. Funded by research grant MH66143 from the National Institute of Mental Health. P1.5.6 ADHD SYMPTOMATOLOGY IN AUTISM: PATTERNS OF PSYCHIATRIC COMORBIDITY AND PSYCHOTROPIC MEDICATION USE . D.A. Pearson and K.A. Loveland. Dept. of Psychiatry, Univ. of TX Med. Sch., Houston, TX 77030. Comorbid psychiatric symptomatology and psychotropic medication use were compared in children with Autistic Disorder (AD) whose symptomatology also met DSM-IV criteria for Attention Deficit Hyperactivity Disorder (ADHD), and in children with AD who did not have symptoms of ADHD. Based on the DICA-IV, the Autism-ADHD group (n=38) had the following comorbid psychiatric diagnoses: Obsessive Compulsive Disorder (OCD, 42%), Oppositional Defiant Disorder (ODD, 39%), Specific Phobia (32%), Major Depressive Disorder (MDD, 21%), Dysthymic Disorder (11%), Social Phobia (11%), Anxiety Disorder (8%), Separation Anxiety (5%), Conduct Disorder (3%), and Anorexia (3%). These children were taking the following psychoactive medications: Stimulants (47%), Antipsychotics (29%), Antidepressants (34%), Mood Stabilizers (11%), Anxiolytics (5%), and Alpha-2 Agonists (11%). Children in the Autism/Non-ADHD group (n=24) had the following comorbid psychiatric diagnoses:

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Specific Phobia (33%), Social Phobia (33%), OCD (25%), ODD (21%), Anxiety (8%), Conduct Disorder (8%), Dysthymic Disorder (8%), MDD (4%), Separation Anxiety (4%), and Bipolar Disorder (4%). Children in this group were taking: Antipsychotics (29%), Antidepressants (34%), Mood Stabilizers (8%), and Anxiolytics (4%). Findings suggest that children with Autism/ADHD are at particularly high risk for OCD, ODD, and MDD. Children in the Autism/non-ADHD group appear to be at slightly higher risk for anxiety and social phobia. Intriguingly, the rate of antipsychotic, antidepressant, and anxiolytic medications use in both groups was virtually identical. Poster Session 1: Topic 6: Diagnosis and

Screening Instruments for Autism Research

P1.6.1 ANOTHER LOOK AT THE SOCIAL COMMUNICATION QUESTIONNAIRE AND ITS RELATIONSHIP TO THE AUTISM DIAGNOSTIC INTERVIEW. C. Corsello, D. Anderson, S. Qiu, S. Risi and C. Lord*. The University of Michigan Autism and Communication Disorders Center, Ann Arbor, Michigan, 48109. The Social Communication Questionnaire (SCQ), formerly the Autism Screening Questionnaire (ASQ), is a screening instrument for Autistic Spectrum Disorders (ASDs), completed by a parent. An initial study reported good sensitivity and specificity of the SCQ in an older sample (ASD mean age = 23 years), with whom the Autism Diagnostic Interview - Revised (ADI-R) was administered prior to the SCQ. More recent studies, with younger children and completion of the SCQ prior to the ADI-R have been less encouraging. Some studies have replaced the ADI-R with the SCQ, for determining eligibility for research studies, reporting good agreement between the measures. The present study examined the effectiveness of the SCQ as a screening instrument in two groups, one of which had the ADI-R prior the SCQ (N= 126) and

the other of which had the SCQ prior to the ADI-R (N = 229), and compared the ADI-R with the SCQ. Findings indicated that sensitivity was higher and specificity was lower for the group that had the ADI-R prior to the SCQ (sensitivity = .80; specificity = .60) than for the clinic referred group that had the SCQ prior to the ADI-R (sensitivity = .66; specificity = .67). The ADI-R was then compared to the SCQ, in the clinic referred sample who had the SCQ prior to the ADI-R. The ADI-R demonstrated higher sensitivity (.76) and specificity (.70) than the SCQ in this sample. Results will be discussed in terms of theoretical and practical implications for screening for research and clinical purposes. P1.6.2 REPETITIVE BEHAVIORS IN AUTISM SPECTURM DISORDERS : RELATIONSHIPS WITH ASSOCIATED CLINICAL FEATURES . R.L. Gabriels,* M. Cuccaro, L.G. Ogden, D.E. Hill and B. Ivers. University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 We examined relationships between RBs and associated clinical features (i.e., cognitive and adaptive functioning levels, sleep problems, medication use, and other behavioral problems) in children with ASD (n = 14). Participants were recruited from an earlier autism outcome study. Adaptive level (Vineland Adaptive Behavior Scales, VABS) (r = -0.83; p < .001), NVIQ (Leiter-R) (r = -0.76; p = .002), and the presence of sleep problems (r = 0.77; p = .001) were highly correlated with total RB scores on the Repetitive Behavior Scale - Revised (RBS-R). After controlling for NVIQ, adaptive level and sleep problems were not significantly associated with RB scores, but there remained a significant positive correlation between the presence of RBs and the Hyperactivity subscale of the Aberrant Behavior Checklist (ABC) (partial r = 0.58, p = .039). No significant associations were observed between medication use and presence of repetitive behaviors. Parent stress ratings were highly correlated (r = 0.84; p<.001) with the presence of RBs. There is a suggestion of a complex relationship between RBs and associated clinical features. The current findings are preliminary and merit further study with a larger sample.

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P1.6.3 PARENT REPORT OF SYMPTOMATOLOGY IN AUTISM SPECTRUM DISORDERS: CHANGE BETWEEN INITIAL AND FOLLOW-UP EVALUATIONS . L. Gilotty, P. Lee, G. Wallace, M.C. Gibbs, D. Black and L. Kenworthy*. Center for Autism Spectrum Disorders, Children’s National Medical Center, Washington, DC 20010. Recent increases in the diagnosis of autism spectrum disorders (ASD) have highlighted the need for valid and reliable diagnostic measures. While clinical experience and clinician judgment is still heavily relied upon to make a diagnosis of an ASD, there is an increasing need for accurate screening measures. One such measure, the Social Communication Questionnaire (SCQ), has been in use for many years and relies upon parent report. However, parental experience with ASD may influence interpretation of and responses to items on parent report screening measures. The present study examines the relationship between parent report on the SCQ at the time of initial evaluation (N=23) and after diagnosis, at the time of re-evaluation (N=18). Findings indicate a significant increase (p<.01, two-tailed) in parent report of symptom severity on the SCQ at the time of the re-evaluation (M=25.33, SD=6.00), in comparison to the initial evaluation (M=17.52, SD=8.30). These results suggest parent report of ASD symptomatology may change significantly after the diagnosis is made. Therefore, the SCQ may be a good initial screening tool, but diagnosis and assessment of symptom severity in ASD may require clinical judgment and administration of structured diagnostic measures. P1.6.4 DIAGNOSTIC STABILITY OVER A 2-YEAR TIME PERIOD IN PRESCHOOLERS WITH AUTISM SPECTRUM DISORDERS. J. Kleinman, J. Pandey, P. Dixon, L. Wilson, H. Boorstein, E. Esser, M. Barton, S. Allen, J. Green, G. Marshia, D. Robins and D. Fein*. University of Connecticut Psychology Department, Storrs, CT 06269; Early diagnosis of Autism Spectrum Disorders (ASD) is crucial for optimal prognosis. However, most diagnostic instruments have been designed for use with school age children, and are not well

validated for use in children under the age of five years. The following study investigated diagnostic stability in a group of 44 preschoolers (mean age 55 months), originally diagnosed with ASD, language delay, or global developmental delay (mean age 26 months). Participants were drawn from a large screening study using the Modified Checklist for Autism in Toddlers (M-CHAT; Robins, Fein, Barton, & Green, 2001) to identify ASD in children between 18-30 months. A number of diagnostic instruments were used in each evaluation, including the ADOS, ADI-R, CARS, and clinical judgment based on DSM-IV criteria. Based on these, 26 children were diagnosed with ASD at both evaluations; 7 children were diagnosed with ASD at time 1, but not at time 2 (they were re-diagnosed as language delayed, mentally retarded, etc.); 0 children were diagnosed with ASD at time 2, but not time 1; 11 children were diagnosed as not being on the spectrum at both evaluations. A chi-square comparison for diagnostic stability is significant, ¡2= 21.185, p < .001. While some children move away from ASD, the stability is generally good and validates diagnosis as early as 2. P1.6.5 LIPIDOMICS IN AUTISM: ALTERATIONS IN WHITE MATTER PHOSPHOLIPIDS. O. Koul, B. Evans and J. Evans. Department of Biochemistry and Molecular Pharmacology, and Shriver Center, 200 Trapelo Road, Waltham, MA 02452. We are investigating alterations in levels of various lipids in white matter from postmortem tissues from autistic individuals. We have previously reported overall differences in amounts of phosphatidyl ethanolamine in corpus callosum between autistic individuals and normal controls. The focus of the current study was to extend our investigation to include other phospholipids and to investigate differences at the level of molecular species, since most phospholipids are made up of a number of molecular species. Lipids were extracted from frozen corpus callosum from autistic individuals and normal controls. Most of the acidic glycolipids, and neutral lipids were removed. The samples were desalted, and dimyristoyl phosphatidyl ethanolamine and phosphatidyl choline (C:36:0) were added as

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internal standards. The extracts were subjected to direct infusion nanospray linked-scan ESI-mass spectrometry for identification and quantification of phospholipids and their molecular species. The phospholipids detected include PI, PE, PS, PC and SM. Since substantial quantities of PE and PC in white matter exist as plasmalogens, an effort was made to identify them as well. Sulfatides were also analyzed. Significant differences were detected in phospholipid and sulfatide molecular species distributions. The data will be presented and discussed in the context of myelin maturity. The investigations were partly supported by a grant from the Stanley foundation. P1.6.6 FAMILY RESOURCES PREDICT AGE AT DIAGNOSIS BEYOND THE COHORT EFFECT . A.S. Carter* and J.C. Kuhn*. Department of Psychology, University of Massachusetts Boston, Boston, MA 02125. There have been multiple efforts to improve early detection of autism spectrum disorders. Few studies have investigated associations between family resources and age at child diagnosis, yet this knowledge could inform early detection efforts. Participants included 146 parents with a child with an autism spectrum disorder who completed an internet survey. Approximately 75% of the children were boys and 13% non-white. In bivariate analyses, there was evidence for a cohort effect, with child age correlated with age at diagnosis (r = .46 p<.001). Further, autism spectrum disorder severity was associated with earlier detection as children with a diagnosis of autism as compared to a diagnosis of PDD or Aspergers were more likely to be diagnosed early (r = .24, p<.01). Finally, the following family sociodemographic characteristics were also associated with age at first diagnosis: 1) parent education (r = .16, p<.05); 2) parent report of difficulty paying bills (r = -.17, p<.05); and 3) parent age (r = .14, p=.05). Income and minority status were not correlated with age at first diagnosis. When entered into a multiple hierarchical regression equation, child age, autism diagnosis, and parent age accounted for unique variance in age at first diagnosis (F(3,142)=19.25, p < .001, Adj. R2 =.274). These findings suggest that early detection efforts

are reducing the age at which children are first diagnosed, with earlier diagnosis for children with more severe symptoms and greater family resources. Greater efforts may be required to reach parents who are younger, less educated, and experiencing financial stress. *Supported by NAAR. P1.6.7 DEVELOPMENT OF THE COMFOR. I.L.J. Noens and I.A. Van Berckelaer-Onnes. Leiden University, The Netherlands. The ComFor (Forerunners in Communication - Verpoorten, Noens & Van Berckelaer-Onnes, experimental version, 2001) is a diagnostic instrument to obtain a precise indication of individualized communicative interventions, in particular augmentative means adapted to the level of perception. The target group consists primarily of people with autism without or only limited verbal communication. The ComFor tries to measure “sense-making” in connection with perception at the levels of presentation and representation for non-transient modalities. The ComFor was administered by 365 individuals with the autistic disorder and mental retardation, and 180 individuals with mental retardation only. The developmental level of all subjects (measured with the Vineland Adaptive Behavior Scales) ranged from 13 to 60 months. People with autism performed strikingly strong on the level of presentation and relatively weaker on the level of representation. The results are discussed in relation to enhanced discrimination and a weaker drive for central coherence in autism. The ComFor has proven to be a very valuable instrument for clinical practice. If communication is tuned to the individual needs, the quality of life for people with autism and mental retardation can increase substantially. The study also yielded some critical considerations on frequently used intervention programs such as TEACCH and PECS. P1.6.8 THE MODIFIED CHECKLIST FOR AUTISM IN TODDLERS: AN UPDATE. J. Pandey, J. Kleinman, P. Dixon, L. Wilson, H. Boorstein, E. Esser, S. Lanz, M. Barton, S. Allen, T. Dumont-Mathieu, J. Green, G. Marshia, D. Robins and D.

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Fein*. University of Connecticut Psychology Department, Storrs, CT 06269; Yale University Child Study Center, New Haven, CT 06520. The Modified Checklist for Autism in Toddlers (Robins, et.al, 2001) is a parent-report checklist to detect Autism Spectrum Disorders (ASD) in 16-30 month old children. Currently 2,528 children have been screened (426 failed initial screener; 155 failed initial screener and phone follow-up and agreed to evaluation). 839 cases passing the MCHAT at 2 have been rescreened (mean age= 47 months). Possible misses were (1) children referred for an ASD diagnosis (n= 4), of whom 1 has been confirmed as a miss, 1 lost, and 2 remain to be seen and (2) children (n= 22) who passed the MCHAT at 2, but failed the rescreen. All 22, however, passed the phone interview. 106 of the 110 possibly ASD children were identified at 2, indicating sensitivity of 96.3%. Of the 2,411 children who passed the initial screener, 2,098 do not have an ASD, indicating specificity of 87% for the screener. Of the 2,411 children who passed the phone interview, 2,369 do not have an ASD, yielding a specificity of 98% for the screener plus phone interview. These data indicate that the MCHAT is a useful and accurate instrument for the early detection of ASD. P1.6.9 AUTISM-SCREENING QUESTIONNAIRE DISCRIMINATES BETWEEN CHILDREN WITH AUTISM, NON-SIBLING CONTROLS AND SIBLINGS. S.M. Stephens-Groff, R.C. Bay and R.D. Melmed. Assist. Prof. in Clin. Ped., Univ. of Az, Sch. of Med.; Adjunct Prof., Az. State Univ., respectively. A 40-item, seven-subscale autism-screening questionnaire was developed and tested by the Southwest Autism Research Center (SARC) Phoenix, AZ. using 577 autistic children, 199 non-sibling controls, and 62 siblings, ages 3-18. Parents or caretakers completed the questionnaires. Subscales assessing social interaction, communication, emotional response, sensory response, daily living skills, and behavior used Likert response sets ranging from 1 (Never) to 5 (Always). Loss of acquired skills was measured as a dichotomy for verbal, gestures, fine and gross motor

skills. Coefficient alphas for all Likert scales exceeded .80. Accuracy, sensitivity, specificity, and 95% confidence intervals were calculated, and cross-validated using a random split-half methodology. Accuracy reflected the proportion of children who are classified correctly by the questionnaire. In the final analysis, subscales were unit-weighted and summed. Discriminant function analysis and receiver operating characteristic analyses were used to identify a cut-off score. For the autistic vs. non-sibling control analysis, overall accuracy was 93.5% (95% CI: 91.7-95.3); sensitivity was 92.5 (95% CI: 90.3-94.7) specificity, 96.4 (95% CI: 93.8-99.0). For autistic vs. siblings, overall accuracy was 92.6 (95% CI: 90.0-94.3); sensitivity was 92.5 (95% CI: 90.3-94.7), and specificity, 88.9 (80.5-97.3). Preliminary results suggest that the SARC Questionnaire discriminates among children with autism, non-sibling controls and siblings. Confirmatory factor analyses are being conducted to more specifically define differences among these groups. P1.6.10 IDENTIFICATION OF PERVASIVE DEVELOPMENTAL DISORDERS IN CHILDREN AND ADULTS WITH MENTAL RETARDATION M. Thys and H. Roeyers. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium, B-9000 The present study aimed to estimate a reliable prevalence rate of pervasive developmental disorders (PDD) in children and adults with mental retardation (MR). Additionally we wanted to detect potential diagnostic problems. The sample comprises 2112 children and adults recruited in facilities and schools from two provinces in Belgium. The Scale of Pervasive Developmental Disorder in Mentally Retarded persons (PDD-MRS, Kraijer, 1999) was selected for the screening. This well studied and widely used instrument can be used with people with all levels of mental retardation, between the ages of 2 and 70 years. The study resulted in two estimates of the prevalence rate of PDD: one based on the classification by the PDD-MRS and one based on the information given by the

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health or educational workers of the facilities and schools. According to facilities and schools the prevalence rate of PDD is 9,3%. The screening with the PDD-MRS resulted in an estimated prevalence of PDD among people with MR of 18%. Various explanations for this discrepancy will be discussed: the level of mental retardation, gender, age, genetic disorders and additional disorders or disabilities. This work is supported by “Vlaamse Vereniging Autisme.” P1.6.11 VALIDITY OF THE PDQ-1 AND ABC AS AUTISM SCREENERS. W. Zahorodny, M. Brimacombe, V. Rodriguez, J. Vidal and M. Goldfarb. New Jersey Medical School, Newark, NJ. Though autism may be discerned in many affected children before age 3, clinical identification and intervention often do not occur until later. There is no widely-utilized autism screener for toddlers. Objective: Assess the reliability and validity of PDQ-1 and the ABC as autism screeners for toddlers. Design/Methods: The psychological development of 180 children (12 months to 36 months) was assessed using the Psychological Development Questionnaire for Toddlers (PDQ-1), the Autism Behavior Checklist (ABC), and the Autism Diagnostic Interview, - Revised (ADI-R). PDQ-1 and ABC scores representing psychological development in 41 subjects (toddlers) with autism were compared to PDQ-1 and ABC scores from 38 toddlers with developmental delay and 100 typically-developing subjects. PDQ-1 and ABC scores of 41 subjects with autism were compared to independently-determined Autism Diagnostic Interview, - Revised (ADI-R) scores (gold standard for autism diagnosis) for this group. Results: Comparison of mean PDQ-1 and ABC scores showed a significant difference between groups (one way ANOVA, F test; P-value<0.001). PDQ-1 and ABC scores were significantly correlated (-0.869; P-value<0.001). Concordance of PDQ-1 score and ABC score with ADI-R total score, ADI-social score, and ADI-communication score at diagnostic threshold levels was 100%. Concordance of PDQ-1 score and ABC score with ADI-repetitive behavior score was 60% and 56%, respectively.

Conclusions: The PDQ-1 and ABC may be useful as autism screeners for children between 12 and 36 months. The brevity of the PDQ-1 and the ease with which it can be administered commend it as an autism screener. Slide Session 1: Topic 1: Structural and

Functional Imaging S1.1.1 fMRI OF EVENT-RELATED RESPONSE TO VISUAL DISTRACTORS IN AUTISM. M.K. Belmonte* and S. Baron-Cohen. Autism Research Centre, Departments of Psychiatry and Experimental Psychology, University of Cambridge, CB2 2AH, UK fMRI and ERP studies of autism and Asperger syndrome (ASD) have indicated abnormally intense and distributed response to sensory input, and a lack of ability to bias this response selectively towards relevant inputs in the presence of distractors. Such perceptual alterations may provide a window to autism's neurodevelopmental roots. fMRI was applied to three groups of right-handed males between the ages of 10 and 15: those with ASD confirmed by ADI-R, brothers of people with ASD with no neuropsychiatric diagnosis themselves, and unrelated normal controls. Subjects attended to the central locations within two 3x3 arrays of coloured, oriented sine-wave gratings presented left and right of fixation for 167ms, and ignored other locations. A forced-choice response indicated the conjunction of a target colour at the centre of one array and a target orientation at the other. Surrounding gratings were either congruent or incongruent with these attended locations. Preliminary results in a small set of subjects replicate the finding of hyper-intense activation in visual cortex. In addition, event-related comparison of the incongruent to the congruent condition reveals in all groups stronger activations for incongruent stimuli in middle frontal gyrus, parietal cortex and anterior cingulum, with frontal and parietal activations in the autism group less spatially focused than in the controls. Quantitative regional effects in all groups will be presented and compared.

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S1.1.2 PROTON SPECTROSCOPY IN DEVELOPMENTALLY DELAYED YOUNG CHILDREN WITH AND WITHOUT AUTISM SPECTRUM DISORDERS. M. Zeegers, J. van der Grond, E. van Daalen, S.H.N. Willemsen-Swinkels, H. van Engeland and J.K. Buitelaar. Department of Child and Adolescent Psychiatry, University Medical Centre Utrecht, The Netherlands. Autism is a severe developmental disorder. Proton MRS is a tool which provides a non-invasive window to brain biochemistry. Previous MRS studies with autistic patients found lower levels of NAA in cerebellum and temporal regions, possibly indicative of neuronal loss, immaturity of neurons or hypofunction of these regions. Most of these studies covered a broad age range, while age can be a confounding factor. We scanned 35 patients between the ages of 2 and 6 with a diagnosis of autism, PDD-NOS, language disorder or mental retardation. The children were scanned during anaestesia. 1HMRS investigations were performed on a 1.5-T whole-body system. On the basis of a 3D-FFE a volume-of-interest (VOI) was placed in the frontal white matter and in the hippocampal/amygdaloid complex. Peaks were identified and measured with VARPRO. After correction for age and developmental level, no differences were found between the autism group and the respective control groups in absolute NAA (mean 9.59, SD 1.20), Cho (mean 2.10, SD 0.88) or Cre (mean 4.97, SD 1.18) in the frontal cortex, nor in the hippocampal/ amygdaloid complex; absolute NAA (mean 6.87, SD 1.45), Cho (mean 1.66, SD 0.61) or Cre (mean 5.05, SD 1.54). Contrary to previous reports, we found no differences between the autism group and the control groups. S1.1.3 AN MRI STUDY OF THE ORBITOFRONTAL CORTEX IN AUTISM . A.Y. Hardan*, A. Lacerda, O. Yorbik, M.S. Keshavan and N. Minshew. University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. Several structures of the prefrontal cortex have been implicated in the pathophysiology of autism including the orbitofrontal cortex (OFC). OFC is involved in multiple cognitive functions such as

emotional and information processing, learning, memory, and social behavior. The present study examined the size of OFC in patients with autism and group-matched healthy controls. MRI scans were performed on 40 non-mentally retarded individuals with autism, and 40 age-, gender-, race-, IQ-matched healthy controls. Total OFC and its medial and lateral subdivisions were measured. When compared to controls, decreased size of the right lateral OFC was observed in children with autism whereas increased size was observed in adults. Results remained unchanged after adjusting for total brain volume. No difference between the two groups where observed in any of the other structures. Interestingly, positive correlations were observed in the total autistic sample between repetitive behaviors including verbal rituals as measured by the ADI-R and total lateral OFC and left lateral OFC. The present study suggests the presence of structural abnormalities in the right lateral OFC in autism indicating that these volumetric alterations may underlie some of the cognitive deficits observed in this disorder especially in light of the recent evidence implicating the OFC in the Theory of Mind and joint attention. Research Support: MH64027 to Dr. Hardan, and HD-35469 and NS-33355 to Dr. Minshew. S1.1.4 NEUROANATOMY IN YOUNG GIRLS WITH AUTISM: A PRELIMINARY STUDY. C.S. Bloss and E. Courchesne.* The Center for Autism Research, University of California, San Diego and Children’s Hospital Research Center. San Diego, CA 92037. Little is known about neuroanatomy in girls with autism due to underrepresentation of this subject group in previous MRI study samples. In the current study, MRI data from 9 girls and 27 boys with autism was compared with data from 14 girls and 14 boys with typical development. The girls and boys with autism were matched with respect to nonverbal IQ. All children were between 2 and 5 years of age at the time of scan. Whole brain, cerebral, cerebellar, and cerebral lobar white and gray matter volume measurements were examined on two levels: (1) between girls with autism and typically developing girls; and (2) between girls and boys with autism.

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Results indicated that relative to typical girls, girls with autism exhibited a pattern of abnormality similar to that previously observed in boys with autism (Courchesne et al., 2001). To compare measurements between girls and boys with autism, values for each region and tissue type of interest were converted to z-scores based on the mean and standard deviation observed in typical girls and boys. Analyses revealed that girls with autism exhibited a greater degree of abnormality with respect to nearly every structure and tissue type observed. Further, girls with autism showed statistically significant enlargement in temporal white and gray matter volume relative to boys with autism; frontal gray matter enlargement approached significance. Cerebellar gray matter volume was significantly reduced in girls relative to boys with autism. Implications for sex differences in base rates and clinical phenotype will be discussed. This work was supported with funds from RO1 NS19855. S1.1.5 AUTISM SPECTRUM DISORDERS AND MACROCEPHALY E. van Daalen, S.H.N. Willemsen-Swinkels, J.K. Buitelaar and H. van Engeland. University Medical Center of Utrecht, P.O. box 85500, 3508 GA Utrecht, The Netherlands. Background: infantile macrocephaly is associated with an increased risk of developing autism spectrum disorders (Bolton et al., 2001). Methods: in a population-based sample of very young children with autism spectrum disorders and other child psychiatric disorders head circumference was measured frequently in the first year of life. At our department two psychiatric assessments and several head Circumference follow-up measurements were conducted before the age of four years. The head circumference measurements were compared with those of population based measurements (TNO, the Netherlands, 1997). Results: Subjects with an autism spectrum disorder showed a significant larger head circumference as compared to population based measurements at eleven months of age (preliminary data). Conclusion: our data suggest an overgrowth of the brain in the first year of life in the children

diagnosed with an autistic spectrum disorder by the age of 42 months. S.1.1.6 CORTISOL DYSREGULATION IN CHILDREN WITH AUTISM . B.A. Corbett,* M. Abdullah, S. Mendoza and S. Levine. UC Davis Department of Psychiatry and Behavioral Sciences. Psychology Department and M.I.N.D. Institute, Sacramento CA, 95817. Children with autism have long been described as experiencing difficulty in tolerating novelty and environmental stressors. We completed a study evaluating the functioning of the limbic-hypothalamic-pituitary-adrenocortical (LHPA) axis in children with autism through the collection of salivary cortisol. The subjects consisted of twenty-two children between 7 to 11-years of age, 12 diagnosed with autism and 10 neurotypical children. We evaluated: 1) the circadian regulation of cortisol, in the home environment, 2) the endocrine stress response (twenty minutes in a mock MRI), and 3) the negative feedback regulation of the adrenocortical response to stress. We predicted that children with autism would show a normal circadian rhythm, an elevation in cortisol in response to stress and a prolonged recovery following a stressful event. The results indicated a significant difference (p<0.01) of values throughout the day suggesting the circadian rhythm in the children with autism is highly variable. Further, the children with autism showed a significant stress response to a non-social environmental stressor (p<0.05) compared to the neurotypical children, which did not exhibit a stress response. The children with autism also showed a more prolonged response (p<0.01) following the stressful event, suggesting poor regulation of the negative feedback system. The findings, implications and future directions will be discussed. Slide Session 1: Topic 2: Autism and Memory S1.2.1 POOR SEMANTIC ACTIVATION AND INTERFERENCE IN AUTISM. K. Boser, H. Haarmann and M. Knobel. Johns Hopkins Univ.,

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Baltimore, MD., 21287 Univ. of MD, College Park, MD 20742. One explanation of the poor recall benefit for semantically related word lists in autism may be impairment of executive functions. However, prior research has not differentiated among specific functions including activation, inhibition or maintenance of meanings. We tested 10-15 yr. old subjects with autism and age-matched controls in two types of tasks involving: (1) activation of semantic associations (2) inhibition or maintenance of meanings. Activation was tested in (1) word recall using cued and uncued semantically related lists and (2) word recognition for semantically similar lists. Inhibition and maintenance was tested in category cued recall for unrelated lists with either no delay, a filled or unfilled 2-sec-delay. Recall of semantically related word lists improved in autistic subjects with experimenter cueing of associations. Additional evidence for impaired activation of associative semantic meanings was found in the word recognition task which led to large proactive interference from related lists for normals but not subjects with autism. In category cued recall, subjects with autism performed worse on filled vs. unfilled delay conditions, and produced more intrusions in the typical short-term portion of the list than controls. These intrusions probably reflect long term memory strategies resulting from a smaller semantic short-term memory capacity. Together, these data argue for impaired semantic memory in the form of poor inhibition of irrelevant information and poor activation for associative word meanings. S1.2.2 EFFECTS OF RELATED AND UNRELATED CONTEXT ON MEMORY IN ASPERGER'S SYNDROME. D.M. Bowler, J.M. Gardiner and S.B. Gaigg. Department of Psychology, City University, London EC1V 0HB, UK Existing research has shown that individuals with autism experience difficulties in using relatedness among studied items to help their free recall (Tager-Flusberg, 1991; Bowler et al. (1997). People with autism have also been reported to have difficulties in recalling the source of studied material, even when recall of the studied material itself is

unimpaired (Bennetto et al., 1996; Bowler et al., in press). Furthermore the theory of Weak Central Coherence (WCC, Frith & Happé, 1994) suggests that people with autism are impaired in their use of contextual information. On the basis of this literature we predicted that, unlike typical individuals, individuals with Asperger's syndrome would not show enhanced recognition memory for words presented alongside a related rather than an unrelated context word. A similar method was used by Mayes et al. (1992) to demonstrate that people with amnesia had a disproportionate memory deficit when interactive context was present. That is when non-studied material that was present at study and was conceptually related to the studied material. Our results did not support the hypothesis. Both groups showed the same advantage in recognition for words presented with related context words. The implications of these findings for theories of autism are discussed. S1.2.3 A PROFILE OF MEMORY FUNCTION IN CHILDREN WITH AUTISM. G. Goldstein, D.L. Williams and N. Minshew. Univ. of Pittsburgh Sch. of Med., Pittsburgh, PA 15213. A clinical memory test, the Wide Range Assessment of Memory and Learning (WRAML), was administered to 38 high-functioning children with autism and 38 individually matched normal controls between 8 and 16 years of age. The status of associative memory and spatial working memory, the ability to spontaneously organize material, and differences between auditory and visual memory were assessed. The profile of major specific abilities and domains of memory functioning was also examined. The results yielded a profile of memory abilities in autism that was substantially different from the profile found in a normal control group. The profile for the children with autism was characterized by relatively poor visual memory, recall of complex language, and spatial working memory with relatively intact associative learning ability, short term memory and recognition memory. Delayed recall was not generally impaired, but was deficient for thematic verbal material as assessed by recall of stories. A principal components analysis indicated that the factor structure of the WRAML subtests

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differed substantially between individuals with autism and controls, suggesting differing organizations of memory ability. A stepwise discriminant function analysis of the WRAML subtests found that the Finger Windows subtest, thought to be a measure of spatial working memory, discriminated most accurately between the autism and normal control groups. This research was supported by NINDS (NS33355) and NICHD (HD35469) grants and by the Medical Research Service, Department of Veterans Affairs. This study was supported by an NICHD Collaborative Program of Excellence in Autism (CPEA). S1.2.4 A FURTHER CHARACTERIZATION OF COMPLEX COGNITIVE ABILITIES IN HIGH FUNCTIONING AUTISM. N. Minshew, D.L. Williams and G. Goldstein, Univ. of Pittsburgh Sch. of Med., Pittsburgh, PA 15213. A study was conducted of abstraction, related conceptual reasoning abilities, and executive function in individuals with high functioning autism. An extensive battery of tests was administered to samples of individuals with high functioning autism and age, education, and IQ group matched normal control participants to assess various aspects of abstract reasoning, problem solving, and executive functioning such as rule learning, concept formation, inductive reasoning, forming mental representations, spontaneous generation of plans, and cognitive flexibility. Data were analyzed by power analysis ranking differences between the autism and control groups in power to reject the null hypothesis. The most powerful tests were those that assessed inductive reasoning through the spontaneous formulation of hypotheses; those that assessed the spontaneous generation of plans leading to a solution; and, those that assessed the shifting or changing of hypotheses when needed. Tests that assessed rule learning, concept identification, concept recognition, simple planning, and divergent thinking did not discriminate between the autism and control groups. Tests of executive function that did not contain a problem-solving component did not discriminate between the groups. The identified deficits are ones that are not reflected in average IQ

scores but have a significant adverse impact on adaptive functioning. This research was supported by NICHD Grant HD35469 and NINDS Grant NS33355 to Nancy J. Minshew and by the Medical Research Service, Department of Veterans Affairs. This study was supported by NICHD Collaborative Program of Excellence in Autism (CPEA). S1.2.5 RELATIONAL AND ITEM-SPECIFIC ENCODING IN FREE RECALL IN ASPERGER'S SYNDROME. S.B. Gaigg, D.M. Bowler and J.M. Gardiner. Department of Psychology, City University, London EC1V 0HB, UK Lovaas etal, 1979) reported that children with autism responded to elements of a complex stimulus in selective ways and concluded that such stimulus overselectivity might contribute to a range of autistic symptoms. The Weak Central Coherence (WCC) account of autism has also documented situations where individuals from the autistic spectrum respond as if they do not integrate elements of a complex situation into a coherent whole. Such failure to integrate items may explain why people with autism do not use inter-item semantic information to help their free recall. Research on memory in typical individuals has shown how encouraging either attention to each individual item or to relations among items affects recall. Starting from the observation that accuracy of recall of items from large categories is worse than that of items from small categories, Hunt & Seta (1984) asked participants to engage in either item-specific or inter-item relational activities at study. They found that the former enhanced recall from large categories, but that the latter enhanced recall from small categories. We predicted that as individuals with autism focus on details, relational encoding should improve memory from large categories. But since they already process in an item-specific way, inducing this encoding strategy would not significantly improve performance. We found the expected effects for the controls but no improvement due to relational encoding for the Asperger group, even though they did improve in the item-specific encoding condition. These findings suggest that

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failure to encode relationally is a core feature of memory in autism. Slide Session 1: Topic 3: Genetics I S1.3.1 FAMILY HISTORY MAY PLAY A ROLE IN THE ASSOCIATION OF SEROTONIN TRANSPORTER GENE (SLC6A4) POLYMORPHISMS IN AUTISM. R. Rabionet (1), A. Konidari (1), C.M. Wolpert (1), S.L. Donnelly (1), R.K. Abramson (2), H.H. Wright (2), M. Cuccaro (1), J.R. Gilbert (1) and M.A. Pericak-Vance*(1). (1) Dept of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710 (2) WS Hall Psychiatric Institute, University of South Carolina, Columbia, SC 29208 Autism has been shown to have a strong complex genetic component, with several interacting genes likely involved. Several genomic regions and many candidate genes have been proposed to be involved in autistic disorder. One of the most consistent findings in autism is platelet hyperserotoninemia. Polymorphisms in the promoter of the serotonin transporter gene (SLC6A4) located on chr.17 have been hypothesized to cause the high serotonin levels in autistic subjects. However association studies of SLC6A4 have produced conflicting results. We performed association analysis using PDT and genoPDT on three SNPs (rs140700, rs1042173 and rs2066713) in SLC6A4 that have been reported to account for all common haplotypes in SLC6A4. Our dataset consisted of a total of 407 families, of which 241 were autism family history positive and 166 were family history negative. The overall dataset showed no evidence of association, however examination of the family history + subset showed significant association for rs140700 (genoPDT=0.004; PDTt=0.02). These data support the role of SLC6A4 in autism susceptibility and suggest that family history may be an important variable to consider when examining the role of SLC6A4 susceptibility in AutD.

S1.3.2 LINKAGE AND ASSOCIATION OF AN ASPARTATE/GLUTAMATE CARRIER WITH AUTISM: GENETIC VARIANTS ARE ASSOCIATED WITH A SEVERAL-FOLD INCREASED RISK . J.D. Buxbaum*, N. Ramoz, C.J. Smith, J.M. Silverman and I. Bespalova. Lab of Molecular Neuropsychiatry, Department of Psychiatry, Mt Sinai School of Medicine, New York, NY10029 A major susceptibility locus for autism was mapped to 2q24-q33. We analyzed genes across this interval to identify an autism susceptibility gene. First, we identified genetic variants in exons and flanking sequence in unrelated subjects showing linkage to 2q24-q33, and compared frequencies between subjects and controls. Second, variants showing nominal association were further genotyped in 411 autistic families, and linkage and association tests were carried out. Linkage and association were observed between autism and two SNPs, both within a gene encoding a mitochondrial aspartate/glutamate carrier (AGC1) that is involved in adenosine triphosphate (ATP) synthesis. Using a single affected per family, evidence for excess transmission was found by the TDT and by TRANSMIT for AGC1-4 (P=0.001 by both tests), AGC1-9 (P=0.01 and 0.007), and a two-locus G*G haplotype (P=0.000003 and 0.004). Linkage analysis with the two SNPs demonstrated a maximal multipoint NPL score of 1.57 and a maximal multipoint heterogeneity LOD score of 2.11. Genotype relative risk (GRR) was estimated at 2-5 depending on number of alleles, although GRR is underestimated in studies such as this. Further studies are needed to confirm this association and to decipher any potential etiological role of AGC1 and mitochondrial function in autism. S1.3.3 POSITIVE ASSOCIATION OF THE GENE CNTNAP2 TO AUTISM-RELATED TRAITS . M. Alarcón, R.M. Cantor, J.L. Stone, S.F. Nelson, AGRE Consortium and D.H. Geschwind*. UCLA Human Genetics and Neurology departments, Los Angeles, CA 90095. Autism is a neurodevelopmental disorder characterized by language impairments, social and

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communicative deficits and repetitive behaviors. We used these endophenotypes in a genome scan to identify quantitative trait loci in 152 families with autism spectrum disorders (Alarcón et al., 2002). The most significant linkage peak was for age at first word (WORD) on chromosome 7q (p = 0.001). Family based association tests were significant for WORD at markers D7S1824 (p = 0.027) and D7S2462 (p = 0.016). The autism sample has doubled and 12 positional candidate genes between these markers were characterized in a subset of the sample (N=212 trios) using 130 single nucleotide polymorphisms (SNP). Association analyses were performed and all of the SNPs were in Hardy Weinberg equilibrium. Family based association tests of the diagnosis of autism spectrum disorder as well as the quantitative traits WORD, age of first phrase (PHRASE) and a composite measure of repetitive behavior were also performed. Results suggest an association of the contactin associated protein-like 2 (CNTNAP2) with broad autism (p < 0.05), WORD (p < 0.05) and PHRASE (p < 0.05). Disruption of CNTNAP2 has been identified in a family with Tourette Syndrome, suggesting genetic overlap of these conditions and making CNTNAP2 a plausible candidate gene (Verkerk et al., 2003). Funding source: R01 MH64547 and U54 MH068172. S1.3.4 GLYOXALASE I AS AN AUTISM SUSCEPTIBILITY GENE . M.A. Junaid*, D. Kowal, M. Barua, P.S. Pullarkat and R.K. Pullarkat. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314. Autism is a heterogeneous, multigenic neurodevelopmental disability affecting children, that is characterized by deficits in verbal communications and reciprocal social interactions, and repetitive behaviors. Studies have indicated a compromised neuronal maturation in autism, and complex inheritance involving interactions of over 10 genes have been proposed in the etiology. Whole genome wide scans for identifying susceptibility genes by and large remained unsuccessful, although several promising chromosomal loci have been observed. Candidate gene search approach has also not

resulted in identification of any major genetic alteration. Using proteomic analyses as an alternate approach, we have identified an acidic form of the enzyme glyoxalase I, Glo1 (lactoylglutathione lyase, EC 4.4.1.5) in several autism brains. Sequencing of the DNA from autism brains has shown a SNP C419A that change alanine with glutamic acid in the protein sequence. A partial dysfunction of Glo1 is observed in the form of reduced enzyme activity, and accumulation of advanced glycation end products (AGE's). Further, the glutamic acid form of Glo1 is hyperphosphorylated. A two-fold increase in the 419A allele frequency was observed in DNA from autism subjects. Glo1 is a detoxifying enzyme involved in scavenging the highly reactive metabolite methylglyoxal formed during the metabolism of carbohydrates, amino acids and fatty acids. The reduced activity of glutamic acid form of Glo1 in autism may lead to accumulation of specific AGE's that interfere with normal brain development. Supported by grants from NIH (NS40691), NAAR and New York State OMRDD. S1.3.5 NOVEL MUTATIONS OF CANDIDATE GENES IN AN AUTISM POPULATION. T. Yamagata, M. Mori, K. Suwa, H. Li and M.Y. Momoi*. Department of Pediatrics, Jichi Medical School, Tochigi, 329-0498, Japan We are analyzing several candidate genes for possible causative mutations among autistic children. The candidate genes analyzed this time were secretin receptor gene (SCTR), FMR1, FMR2 and the genes on 7q such as WNT 16 and GRM8. SCTR were considered as a candidate gene because of the treatment of secretin for autism and the knockout mouse analysis. FMR1 and FMR2 were responsible genes for fragile X syndrome and FRAXE mental retardation that have autistic phenotype. Japanese patients diagnosed with PDD-NOS or autism according to the criteria of DSM-IV were enrolled in this study after the informed consents by their parents. And also DNAs from AGRE were analyzed for some genes. All exons were amplified by PCR, the heteroduplex was made and detected by DHPLC method, and the base changes were confirmed by direct sequencing.

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In SCTR, FMR1, FMR2 and GRM8, we detected several SNPs but not disease causative mutation. In WNT16, a missense mutation (R137K) was detected in one male patient and his seemingly unaffected mother, but not in control. This changed amino acid was the conserved residue between mouse and human WNT16 protein. This result suggested WNT16 is a susceptibility gene of autism disorder and further study on its contribution to autism is needed. This work was supported by the grants from the Ministries of Education, Science and Culture, Japan, and The Japan Health Sciences Foundation. S1.3.6 THE PLATELET HYPERSEROTONEMIA OF AUTISM: INVESTIGATING THE PHENOTYPE AND THE GENETIC DETERMINANTS. E.J. Mulder, G.M. Anderson*, J.A. den Boer, I.P. Kema and R. Minderaa. Child & Adolescent Psychiatry Center, PO Box 660, 9700 AR Groningen, the Netherlands. Recent neurogenetic research findings increased interest in the role of serotonin (5-HT) transporter gene (HTT) variants or mutations in autism. Studies of amygadalar activation and the influence of trauma on depression found major effects of the HTT promoter variant (5-HTTLPR), while an HTT gain-of-function mutation was found to associate with compulsive behavior and social problems. Three recent genome screening studies reported their highest linkage scores in the vicinity of HTT on chromosome 17q11-12. We will overview recent relevant HTT research and present our own findings regarding the platelet hyperserotonemia of autism, heritability of plt 5-HT, functionality of the 5-HTTLPR polymorphism and behavioral association studies examining the effects of the 5-HTTLPR and intron2 VNTR variants. High heritability estimates were observed for plt 5-HT levels; thus, the measure appears to be highly genetically determined. The 5-HTTLPR polymorphism is highly functional, in that plt 5-HT uptake rates vary significantly with genotype. However, a 5-HTTLPR variant does not appear to contribute substantially to the elevated platelet levels seen in autism. New findings in a Dutch population confirm that the hyperserotonemic phenotype is specific to pervasive developmental disorder (PDD)

or autism spectrum, with group mean elevations occurring in autism and PDD-not otherwise specified, but not in non-autistic mental retardation. This study has also, for the first time, demonstrated a bimodal distribution of plt 5-HT within PDD. Finally, an association was observed between compulsive behavior in individuals with PDD and intron2 alleles. Slide Session 1: Topic 4: The Gut, Toxins, &

Nutrients & Autism S1.4.1 NUTRIENT, TOXIN AND ENZYME PROFILE OF AUTISTIC CHILDREN . T. Audhya. Vitamin Diagnostics Laboratory*, Rt. 35 & Industrial Drive, Cliffwood Beach NJ 07735. W.R. McGinnis, 944 Pinecrest Terrace, Ashland OR 97520. Gastrointestinal and anti-oxidant enzyme status of autistic children differ from controls, and this may have nutritional or toxic implications. This study compared nutrients, toxins and enzymes of interest in autistic children and age-matched controls. Autistic Spectrum Disorder by DSM-IV was certified by a psychiatrist and subjects were supplement-naive. Cohort size ranged between 24 and 55 autistics. Individual differences were evident, but lower vitamins and minerals, higher toxins, and altered enzyme activity were found in the autistic group. Vitamins were lower in plasma. RIA: vitamin B12 (p<0.001) and folic acid (p<0.01). HPLC/MS: vitamin B3 (p<0.01) and vitamin A (p<0.05). HPLC: vitamin C (p<0.01). Spectroscopy: vitamin E (p<0.01). Minerals were lower in red cells. ICP/MS: zinc and selenium (p<0.001), magnesium (p<0.01) and copper (p<0.05). Toxins were higher in red cells. ICP/MS: total mercury and organic mercury (p<0.001), arsenic and lead (p<0.01). Toxins were higher in plasma. HPLC/MS: perchlorethylene, hexane, pentane (p <0.01) and xylene (p<0.05). Enzyme activity was altered in red cells. As an indicator of vitamin B6 activity, lower EGOT (p<0.05). As an inverse reflection of binding affinity, Km of pyridoxal kinase (for pyridoxal): autistic 79 ±

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22 µM, control 3 ± 1µM. Km of glutamic acid decarboxylase (for pyridoxal-5-phosphate): autistic 11 ± 5 µM, control 0.2 ± 0.1µM. Km ranges were broad, but by non-parametric statistical analysis, the Km ranges were statistically different (p<0.001). Expenses were offset by Vitamin Diagnostics Laboratory. S1.4.2 GASTROINTESTINAL ABNORMALITIES IN CHILDREN WITH AUTISTIC SPECTRUM DISORDER. S. Levy, M. Souders, R. Ittenbach, J. Pinto-Martin and the PA-CADDRE. Children's Hospital of Philadelphia 3405 Civic Center Boulevard Philadelphia, PA 19104 One popular treatment for children with Autistic Spectrum Disorders (ASD), the gluten free/casein free diet, has widespread implementation despite lack of controlled trials examining efficacy. Treatment is closely tied to the observation that children with ASD have increased frequency of GI symptoms (e.g., constipation, diarrhea, gastroesophageal reflux, and food selectivity, including excessive carbohydrate ingestion). The aim of this study is to determine the frequency of GI symptoms in a well-defined cohort of children with ASD and determine the relationship to dietary intake. Subjects were a convenience sample of 62 children (ages 3-8 years) with ASD who participated in a double blind placebo controlled crossover trial of intravenous synthetic human secretin. Diagnosis was confirmed by ADI-R and DSM-IV criteria. Laboratory data included IgG & IgA antigliadin antibodies, IgA antiendomyseal antibodies, serum transglutaminase, stool pH, and exam for ova and parasites. Each family completed a 3-day diary of the child’s stool frequency and diet history. A registered dietician analyzed the diet histories for RDA intake of calories, protein, carbohydrate, fat and micronutrients. Results of and relationships between gastrointestinal symptoms and nutritional analysis of dietary histories will be presented. S1.4.3 TREATMENT OF CHILDREN WITH AUTISM WITH LOW DOSE COD LIVER OIL M.N. Megson, M.D. F.A.A.P. Pediatric and Adolescent

Ability Center 7229 Forest Aveune, Suite 211 Richmond, Virginia 23226 Many nutritional supplements are used to treat children with Autistic Spectrum Disorder but little data is published in peer reviewed journals concerning their efficacy. This trial investigates if patients diagnosed with Autism improve functioning after supplementation with low dose cod liver oil. We completed a randomized aged matched double blind placebo controlled trial in 38 children with autism over six months in a private outpatient developmental pediatric practice. Prior to enrollment, proof of meeting diagnostic criteria for autism was verified by extensive parent questionnaires, and copies of previous formal evaluations, plus evaluation by DSM IV checklist and Developmental Assessment. All participants received lose doses of bethanecol in second three months of the study. Research assistants administered standardized tests including the Gilliam Autistic Rating Scale, the Autism Behavior Checklist, and the Autism Treatment Evaluation Checklist to measure multiple areas of functioning in the children. Multivariate analysis of all three instruments with combined scoring led to the finding that treatment significantly reduced the global scores as a group. (p=0.01) Daily intervention with low dose cod liver oil may improve functioning in Autistic children. Larger trials are needed to prove or disprove this association. All children showed improved scores, suggesting a positive effect of cod liver oil and the placebo, which needs further study. There was no fudning for this study. We are indebted to Kirkman Labs for providing the cod liver oil and the placebo. Approved by American College for Advancement in Medicine Institutional Review Board. May 1999. S1.4.4 TOXIC AND ESSENTIAL METALS IN BABY HAIR OF CHILDREN WITH AUTISM. J.B. Adams and J. Romdalvik. Arizona State University, Tempe, AZ 85287-6006 A previous study by A. Holmes et al. found that children with autism had much lower levels of mercury in their baby hair (1/8 normal), and that the level of mercury had an inverse correlation with the

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severity of autism. This suggested an inhibited ability to excrete mercury, possibly leading to higher levels in the body. Also, a previous study of metals in hair of 101 children by J.B. Adams et al. found that children with autism had much lower levels of iodine than age and gender-matched controls (-45%, p=0.005), and the children had lower levels of lithium (-30%, p=0.05) as did their mothers (-56%, p=0.005). Low iodine is the leading worldwide cause of mental retardation, and low lithium is associated with a wide range of behavioral problems and impaired immune systems. In this replication study we are investigating the level of toxic and essential metals in the baby hair of children with Autism vs unrelated typical controls, and also comparing against a wide range of symptoms of autism using the ATEC. Results are pending and will be presented at the meeting. Funded by the Autism Research Institute (ARI) and the National Institute for Environmental Health Sciences (NIEHS). Slide Session 1: Topic 5: Epidemiology Risk

factors and Biomedical Associations

S1.5.1 MATERNAL AUTOIMMUNE AND ALLERGIC DISEASES AND CHILDHOOD AUTISM. L.A. Croen*, C.K. Yoshida, R. Odouli and J.K. Grether. Kaiser Permanente Division of Research, Oakland, CA, 94612. To explore the association between maternal autoimmune and allergic diseases and childhood autism spectrum disorders (ASD), we conducted a case-control study among children born at a Kaiser Permanente Northern California (KPNC) facility between 1995-1999. Cases (n=407) were children with an ASD diagnosis (ICD-9-CM 299.0, 299.8) recorded in KPNC outpatient databases. We randomly sampled controls (n=2095) from the cohort of births without an ASD, frequency matched to cases on gender, birth year, and hospital of birth. Maternal autoimmune and allergic diseases

diagnosed from two years preceding delivery to two years following delivery, as well as information on several maternal and infant characteristics, including maternal medication use in the year prior to delivery, was obtained from health plan and vital statistics databases. Significantly more case than control mothers were diagnosed with psoriasis (2.7% vs. 0.95%, p=0.004), type 1 diabetes (1.2% vs. 0.43%, p=0.048), asthma (15.5% vs. 10.5%, p=0.003), and allergic rhinitis (20.9% vs. 14.5%, p=0.001). The frequency of maternal asthma and allergies increased significantly with increasing numbers of ASD-affected children in the family (asthma: Ç2trend=9.49, p=0.002; allergies: Ç2trend=8.94, p=0.003). After adjusting for maternal age, race/ethnicity, education, medication use, and plurality, maternal second trimester diagnoses of asthma or allergy were twice as common in cases than controls (asthma: OR=1.9, 95% CI 1.0-3.7; allergy: OR=2.3, 95% CI 1.1-4.8). These results suggest that maternal immune function during pregnancy is associated with risk of ASD. S1.5.2 HEAD CIRCUMFERENCE IN AUTISM SPECTRUM DISORDERS: A CPEA NETWORK STUDY. J.E. Lainhart, E. Dinh, H. Coon, E.D. Bigler, W. McMahon, The University of Utah, Salt Lake City, UT 84103 and the NICHD CPEA Network. Macrocephaly occurs in approximately 20% of individuals with autism. Studies suggest that the distribution of head circumferences (HC) in autism is bimodal. This project assessed HC, and its relationship to height and clinical variables, in 350 individuals with idiopathic autism spectrum disorders (ASD) (270 autism, 28 Aspergers, 52 PDD-NOS) and 123 typically developing controls. Individuals with ASDs meet Autism Diagnostic Interview, Autism Diagnostic Observation Schedule, and DSM-IV criteria. Mean standardized HC for controls is 0.121, for Aspergers 0.466, for PDD-NOS 0.473, and for autism 0.681. Macrocephaly is present in 17.5% of individuals with autism vs. 6.5% of controls (p<.0005). Macrocephaly occurs at intermediate rates in Aspergers and PDD-NOS. The distribution of standardized HCs is normal in shape for autism and the total ASD group (admixture analysis: chi square = 1.85, df = 3, NS). The normal distribution of

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HC in autism has important implications for genetic and neuroimaging research. Biological mechanisms increasing head and brain size appear to be operative in the population of individuals with autism and ASDs. Neuroimaging research needs to take into account the wide range of head and brain sizes in the disorder and uncover the anatomic brain basis of increased head size in autism. Funding: NICHD 5 HD035476-07, the NICHD Collaborative Programs of Excellence in Autism. Additional support to the University of Utah Site: Utah Autism Foundation and Valley Mental Health. S1.5.3 PERVASIVE DEVELOPMENTAL DISORDERS IN CANADA - POPULATION COMPARISON ACROSS TWO CANADIAN PROVINCES. H. Ouellette-Kuntz*, H. Coo, C.T. Yu, A.E. Chudley, A. Noonan, M. Breitenbach, N. Ramji, T. Prosick, A. Bedard and J.J.A. Holden. The ASD-CARC Epidemiology Project Team. *Department of Community Health and Epidemiology, Queen’s University, Kingston, Ontario, Canada, K7M 8A6 The Epidemiology Project Team of the Autism Spectrum Disorders - Canadian-American Research Consortium (ASD-CARC) has established the National Epidemiologic Database for the Study of Autism in Canada (NEDSAC). Our aim is to longitudinally estimate the prevalence of pervasive developmental disorders (PDDs) in various regions of Canada, and to examine temporal and geographic variations in rates and characteristics of the study population. Regional teams have been established in six provinces to monitor the prevalence of PDDs among children 14 years of age and younger on a calendar-year basis. Service providers and diagnostic centres are the primary sources of case ascertainment. Data collection has been completed for 2002 in Prince Edward Island (PEI) and Manitoba. Prevalence for children 2-14 years of age was 37.7 per 10,000 (95% CI: 30.3-46.5) in PEI and 29.4 per 10,000 (95% CI: 27.0-31.9) in Manitoba. The mean age at diagnosis in PEI was 49.9 months compared to 52.3 months in Manitoba. In Manitoba, children of aboriginal identity with PDD (7.7%) were significantly underrepresented compared to the general population of aboriginal children living off reserves (15.6%) (95% CI for difference in

proportions: 5%-11.3%). The significant difference in prevalence of PDDs between the two provinces will be discussed in relation to our expectations of case capture and diagnostic validity across the two jurisdictions. S1.5.4 THE CO-OCCURRENCE OF AUTISM AND BIRTH DEFECTS. D. Schendel, R. Wines, C. Moore and T. Karapurkar. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-86, Atlanta, GA 30333. The co-occurrence of autism and birth defects may elucidate factors acting during fetal development to cause autism. Studies have described birth defects among children with autism, but not assessed the risk for autism given the presence of specific birth defects in a population-based sample. To achieve both goals, this study linked two surveillance programs: the Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) and the Metropolitan Atlanta Congenital Defects Program (MACDP). The study population consisted of Atlanta 3-year survivors, 1986-1993 (N=293,294), and identified by MACDP with major birth defects (N=9354) or MADDSP with autism (n=617). Among children with autism, 6.6% had a birth defect (versus 3% in the general population), mainly CNS (1.6%) and genitourinary defects (1.3%), and Down syndrome (0.6%) and primarily among boys (sex ratio = 9:1; excluding genitourinary defects=7:1). Among children with birth defects, the prevalence of autism per 1000 children was 4.4 (versus 2-6 per 1000 in the general population), 19.6 among children with CNS defects, 3.1 among children with genitourinary defects, and 17.1 in children with Down syndrome. Having a birth defect doubled the autism risk, but the specific defect distribution does not suggest a common etiologic mechanism leading to autism. Funding was provided through the US Department of Health and Human Services, Centers for Disease Control and Prevention. S1.5.5 AGE AT FIRST MMR VACCINATION AMONG CHILDREN WITH AUTISM AND

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SCHOOL-MATCHED CONTROLS IN METROPOLITAN ATLANTA . W. Thompson*, T. Karapurkar, F. DeStefano, M. Yeargin-Allsopp and C. Boyle. CDC, Atlanta, GA 30333. We assessed whether age at first MMR vaccination was associated with autism. Case children (N=624) were identified from multiple service providers and matched to control children (N=1,824) on age, sex, and school. Vaccination data were abstracted from school vaccine records required for school entry. Children born in Georgia were linked to state birth certificates which allowed for adjustment for maternal and birth factors. Conditional logistic regression was used to estimate odds ratios (OR). Distributions of ages at first MMR vaccination were similar and the majority of cases (70.5%) and controls (67.5%) were vaccinated between 12 and 17 months. Similar proportions of cases and controls were vaccinated before 18 and 24 months of age. There were no significant associations for either age cut-off for specific case subgroups. More cases (93.4%) than controls (90.6%) were vaccinated before 36 months; OR=1.49 (95% confidence interval, 1.04-2.14) in the total sample and 1.23 (0.64-2.36) in the birth certificate sample. These associations were strongest in children aged 3 to 5 years. Similar proportions of cases and controls were vaccinated around recommended ages (i.e., before 18 months) and before the age atypical development is usually recognized in children with autism (i.e., 24 months). Vaccination before 36 months was more common among cases, particularly in children 3-5 years old, likely reflecting immunization requirements for enrollment in early intervention programs. Slide Session 1: Topic 6: Autism, Genes, and

Environment S1.6.1 CHILDREN’S ENVIRONMENTAL HEALTH: ISSUES AND CHALLENGES. E.K. Silbergeld. Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore MD 21205.

The current international focus on children’s environmental health is appropriately based upon considerations of both exposure and response. That is, because of diet and normal childhood behaviors, children are in many cases more intensively exposed to environmental pollutants in air, water, soils, and food. Second, the prolonged period of development of many complex systems, including the CNS, reproductive and immune systems, provides an extended window for differential responses, many of which may persist into adulthood. In addition, two new concepts in environmental health research are relevant for identifying and understanding potential risks to children’s neurological development: the gene:environment paradigm, and the role of early exposures in adult disease. Genetic polymorphisms can confer susceptibility to neurotoxic agents, and fetal (and perinatal) exposures to toxic agents can alter organizational events in complex systems, including the brain. These concepts will be discussed through the examples of multiple gene:environment interactions that modify individual response to lead and arsenic; the effects of prenatal exposures to bisphenol A on the cytoarchitectural organization of the CNS, and the persistent effects of low level exposures to methyl mercury on later host response to infection and consequent autoimmune disease. S1.6.2 EXPOSURES TO METALS AND NEURODEVELOPMENTAL DISORDERS IN CHILDREN. D.C. Bellinger. Harvard Medical School Children’s Hospital Boston In the last 50 years, considerable effort has been devoted to determining whether a child’s exposures to environmental chemicals increase the risk of neurodevelopmental disorders. Inorganic lead and methylmercury are the two most intensively studied metal compounds and, for both, the outcomes of greatest interest have been disorders of cognition. Risk assessments underlying exposure standards for both metals have used cognitive dysfunction as the critical health effect. Only recently have investigators evaluated the hypothesis that children’s metal exposures might also be risk factors for psychiatric disorders, and the data are sparse.

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Some reports suggest that elevated lead exposure places a child at increased risk of autism, ADHD, delinquency, and criminal activity. Some have hypothesized that exposure to ethylmercury, formerly used as a vaccine preservative, increases a child’s risk of autism, but to date studies provide little evidence to support this. One striking characteristic of the dose-effect relationships linking chemical exposures and neurodevelopmental outcomes is the large amount of scatter of observations around the best-fit lines. Some is likely to reflect errors in measurement of exposure, outcome, and covariates, but some might reflect individual differences in susceptibility due to nutritional status, social environment (e.g., SES), genotype, or other factors. Limited efforts have been made to identify genetic bases of susceptibility to metal neurotoxicity. Studies have shown that several genetic polymorphisms (δ-ALA-D, the vitamin D receptor, apolipoprotein E, the HFE protein) are involved in lead toxicokinetics and/or toxicodynamics, but little work has demonstrated effect modification for neurodevelopmental endpoints S1.6.3 EPIDEMIOLOGIC EVALUATION OF GENE-ENVIRONMENT INTERACTION IN CAUSATION OF AUTISM. J.K. Grether. California Center for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) The dramatic increase in the number of children diagnosed with autism in recent years suggests the possibility that new and/or increasingly common non-genetic factors may be etiologically important. Published twin studies, conducted before the recent reports of an increase in observed cases of autism, have contributed evidence supportive of a strong genetic component to autism, modulated by epigenetic or non-genetic factors. Epidemiological studies can serve as a bridge between basic science and clinical approaches. In the context of a population-based design, such studies are well-suited for evaluating the interplay of specific genetic and non-genetic factors and estimating the magnitude of their contribution to the rate of autism. This presentation will explain the relevance of epidemiologic approaches to understanding autism and provide an overview of studies currently

underway in the U.S., particularly etiologic studies funded under the CDC CADDRE network and other studies being conducted through the MIND Institute/UC Davis and the Northern California Kaiser-Permanente Health Care System. These studies use multiple data collection strategies including clinical assessments, parental interviews and self-administered questionnaires, medical record abstraction, and biologic sampling for analysis of environmental exposures, candidate genes, and other biologic markers. Collectively, they provide a comprehensive epidemiological approach that combines testing of hypothesized risk factors with “fishing expeditions” to find new clues. Wherever possible, these studies have been planned in coordination with each other to maximize their power and to attempt to replicate each others results. S1.6.4 IMPACT OF ENVIRONMENTAL CHEMICALS ON NEUROPSYCHOLOGICAL DEVELOPMENT OF CHILDREN: WHAT CAN WE LEARN FROM ANIMAL MODELS? S.L. Schantz. Department of Veterinary Biosciences and Neuroscience Program, University of Illinois at Urbana-Champaign. In our modern world children are exposed to a host of toxic chemicals—beginning in the womb and continuing postnatally. It has been suggested that exposure to some of these chemicals including lead, methyl mercury (MeHg) and polychlorinated biphenyls (PCBs) may contribute to neurodevelopmental disorders such as ADHD and autism. There is currently no definitive evidence to support such a link. However, animal models of early chemical exposures could still prove useful in understanding the etiology of these neurodevelopmental disorders. Early exposure to lead, MeHg or PCBs is known to impair cognitive and sensory function in both primate and rodent models. Some of the deficits observed after chemical exposure are remarkably similar to those observed in human neurodevelopmental disorders. Although less extensively studied, these chemicals also produce alterations in social behavior that resemble those associated with autism and ADHD. These include reductions in social play and

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increases in passive, repetitive and stereotyped behaviors. Comparisons of the behavioral profiles seen in lead, PCB and MeHg exposed laboratory animals to those observed in human disorders such as ADHD and autism may provide useful insights into the functional deficits associated with these debilitating childhood diseases. Poster Session 2: Topic 1: Genetics P2.1.1 THE ROLE OF MeCP2 IN GENE EXPRESSION REGULATION DURING NEURONAL DIFFERENTIATION . S. Peddada and J.M. LaSalle*. Med Micro& Immuno, UC Davis Sch.of Med., Davis, CA 95616 Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2 gene, encoding methyl-CpG binding protein (MeCP2). Elevated MeCP2 expression is acquired in the individual neurons during post-natal human brain development. The function of MeCP2 in the developing brain is unclear at this stage, but the mutations in Rett syndrome and the Mecp2 null mouse model provide evidence that MeCP2 is essential for neuronal maturation. Elevated MeCP2 expression is hypothesized to be required for neuronal differentiation by the regulation of multiple target genes, but identifying such genes in a complex organ like brain has proven difficult. To identify the new genes regulated by MeCP2 during neuronal differentiation, two controlled cell culture systems were developed: the SH-SY5Y human neuroblastoma cell line and NTERA-2 cl.D1 human teratocarcinoma cell line. Both these cell lines can be induced to differentiate into post-mitotic neurons by treating with phorbol ester, PMA or retinoic acid. Upon differentiation they showed elevated levels of MeCP2 prior to exhibiting the mature neuronal phenotype. In order to identify the genes regulated by MeCP2 during differentiation both the cell lines will be transfected with oligodeoxynucleotide decoy to block endogenous MeCP2 binding to methylated CpGs. Gene expression profiles of the cells transfected with wild type decoy will be compared by expression microarray analysis to cells transfected with a mutant control decoy. The results from these

studies are expected to provide novel gene targets regulated by MeCP2, which might provide new information in understanding pathogenesis of wide spectrum of neurodevelopment disorders. Funding- NIHJ, RSRF P2.1.2 INSISTENCE ON SAMENESS AND BLOOD SEROTONIN IN INDIVIDUALS WITH AUTISTIC DISORDER. R.K. Abramson, A.V. Hall, S.A. Ravan, M. Cuccaro, E.H. Cook and H.H. Wright.* Dept Neuropsychiatry, Univ S Carolina Sch Med, Columbia, SC 29203. AD is a genetic neurodevelopmental disorder characterized by deficits in language and social relationships and patterns of compulsive/stereotyped behaviors and rigidity. Cuccaro (2002) identified a factor IS derived from the Autism Diagnostic Interview -Revised (ADI-R). Using ordered subset analysis, IS enhanced linkage to chromosome 15 in a subgroup of families (Shao et al, 2003). Sutcliffe (2002) reported linkage and association of haplotypes at the 5HT transporter locus in a subgroup of individuals with AD with a rigid-compulsions factor derived from the ADI. Elevated blood 5HT is found in a about 30% of individuals with AD. This study examines the association between 5HT and IS in 58 South Carolina probands identified from the Duke/Univ of South Carolina study. 5HT in black probands (X=359.7±SE44.9, n=17) was significantly different (t(1,56)=3.289, p=0.004) than in white probands (X=204.63±SE14.3, n=41). There was no seasonal variation in the control population. Parent reported IS scores in black probands (X=2.24±SE0.585) were significantly lower (t(1,56)= -2.132, p=0.037) than in white probands (X=3.46±0.282). There was a significant positive Pearson Correlation coefficient between race and IS (r=0.274, p=0.05, n=58) and a significant negative correlation between race and 5HT (r=-0.496, p=0.01, n=58). The correlation between IS and 5HT was not significant in this sample. There have been conflicting studies that link 5HT level to the 5HT transporter on chromosome 17. Further study is necessary to evaluate whether the factor used in the Sutcliffe study which is linked to chromosome 17, is associated with 5HT level.

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P2.1.3 DBH POLYMORPHISMS AND SERUM ACTIVITY IN AN FAMILY BASED IRISH POPULATION SUFFERING AUTISM. J. Conroy, N. Murphy, E. Meally , G. Kearney, M. Fitzgearld, G. Anderson, M. Gill and L. Gallagher. Smurfit Institute, Dept.s of Genetics and Psychiatry, Trinity College Dublin, Ireland and Child Study Center, New Haven, CT 06516, USA. Autism is a neurodevelopmental disorder of childhood affecting three core areas of communication, social interaction and behaviour. Genetic factors have been implicated in the aetiology. A number of candidate genes have been investigated, including Dopamine ²-hydroxylase (DBH). This catalyses the conversion of dopamine to noradrenaline and is released into circulation from sympathetic nerve terminals. This study looks at the relationship between DBH alleles and activity levels and autism. The transmission of five polymorphisms within the DBH gene, were tested using TDT. Two of these polymorphisms were in the promoter region of the gene (C-2124T and C-1021T) and included the functional variant C-1021T. Polymorphisms were also investigated in exon 2, exon 5 and exon 12. There was increased transmission of the G allele of exon 5, (TDT chi sq = 4.2828 p = 0.0385). Another three polymorphisms are been presently investigated, including two in the promoter. Haplotype data will be presented. DBH Activity was also investigated. Probands with autism had lower DBH activity than either parent or than the parental mean and these differences were statistically significant (t test p-values ranging between 0.006 and <0.001). Further investigation is needed to identify the causative polymorphism / set of polymorphisms for the lower activity levels in the individuals suffering autism. This work was funded by the Health Research Board, Ireland, Wellcome Trust and National Alliance for Autism Research. P2.1.4 MUTATION SCREENING AND EXPRESSION ANALYSIS OF A CANDIDATE GENE FOR AUTISM. J.A. Duvall 1, J. Simon 4, K. Wilkes 2, J.L. Stone 1, S.F. Nelson 1, E.H. Cook 3, D.H. Ledbetter 3,5, C.L. Martin 3 and D.H. Geschwind 2*. 1)Depts. of Human Genetics, and

2)Neurology, UCLA Sch. of Med., LA, CA 90095; 3)Dept. of Human Genetics, Univ. of Chicago, Chicago, IL 60637; 4)Schering-Plough Research Inst., Kenilworth, NJ 07033; 5)Dept. of Human Genetics, Emory Univ., Atlanta, GA 30322 . Numerous family and twin studies provide compelling evidence that autism has a significant genetic component. Recent work by Martin et al. (AJHG 2003, p.325) has identified an autistic patient with a chromosomal translocation that disrupts the A2BP1 (ataxin-2 binding protein-1) gene on the short arm of chromosome 16. The breakpoint of this translocation is in the first intron of A2BP1, which presents the possibility that RNA and protein expression may be decreased due to nonsense-mediated decay. We have begun analyzing expression by semi-quantitative rtPCR and Western blot analysis. Preliminary data suggest that both the RNA and protein expression are reduced in this individual compared to unaffected family members. To test whether mutations in this same gene may underlie the mutational basis of autism in other autistic patients showing genetic linkage to this region, we are sequencing all exons of A2BP1 in one sib from each of 90 sib pairs showing allele sharing over this region. Thus far, no significant mutations have been identified. Identification of disease-associated mutations in A2BP1 in this sample would provide compelling evidence that A2BP1 influences susceptibility to autism and would greatly aid in elucidating the mechanisms underlying autism and similar disorders. Supported by NIH/NIMH grant R01 MH64547. J.A.D. supported by an award from the M.I.N.D Institute, UC Davis. P2.1.5 CHROMOSOME X-WIDE ASSOCIATION STUDY IN AUTISM. J. Gauthier, R. Joober, J. St-Onge, A. Bonnel, D. Gariépy, H. Lacasse, D. Verlaan, R. Najafee, É. Fombonne, L. Mottron and G.A. Rouleau. Research Institute of the McGill University Health Center, 1650 Cedar Ave, Montreal, H3G1A4, Canada It is now well known that genetic factors play an important role in the pathogenesis of AD. So far

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many loci on several chromosomes have been associated but none have been clearly associated with the pathogenesis of autism. The higher prevalence of AD in male, the higher than expected prevalence of Fragile X among autistic subject, monosomy X in females with maternally inherited X chromosome, Xp deletion, and X;8 translocation are lines of evidences that chromosome X may harbour a candidate gene for autism. Moreover, four out of six genome-wide scans reported suggestive linkage to the X-chromosome. We tested using a family-based association study approach the implication of the X chromosome in 119 unrelated trios presenting affected autistics offspring. We used 13 highly polymorphic covering the whole X chromosome. In addition 3 known SNPS within the MAOA genes were analyzed. We did analyze our data by dividing in two subgroups base on their ethnicity: (1) French-Canadian (FC), or (2) Non-French-Canadian (NFC). In addition, we stratified those two subgroups by gender: (3) FC males, and (4) NFC males. We performed the test for multiallelic markers using the likelihood-based Extended TDT. Four markers were found to be positive for association, DXS8043, DXS6789, DXS1047 and DXS998. Except for DXS8043 all of them already had been reported to be link to AD. The results of our family-based analyses study provide support for X-linked loci as predisposing to AD. Ethnic stratification may provide greater power to fine map disease genes especially in complex traits. P2.1.6 BIOMARKER DISCOVERY THROUGH GENOMIC-ARRAY PROFILING OF AUTISM J. Gregg*, W. Zhang, C. Baron and D. Milliken. M.I.N.D. Institute, Departments of Pathology. Autism is characterized as a pervasive neurodevelopmental disorder with onset before 30-36 months of age, resulting in impairment of social interaction and communication, and manifestation of repetitive stereotypic behavior. The involvement of genetic factors for autism has been well established in family and twin studies. In addition, there is emerging evidence that the presence of chromosomal abnormalities may play a significant role in the etiology of autism; in particular, cytogenetically detected deletions on 15q and 7q

have been described. Because techniques such as high-resolution cytogenetics and now-classical chromosomal genomic hybridization (CGH) have limited chromosomal resolution (>5 Mb), there is great potential to miss disease-associated smaller –cryptic- chromosomal deletions or amplifications. We hypothesize that with this limited resolution scanning of the genome, there are autism-associated small cryptic (<5Mb) chromosomal aberrations that remain systematically undetected. Recently, the advent of BAC arrays and oligonucleotide arrays has yielded high-resolution genomic scans (currently at d1 Mb) in a rapid and highly reproducible fashion. We have used the BAC and oligonucleotide array technology and demonstrate that it provides accurate quantitative measures of genome copy number in predefined patients with chromosomal abnormalities. We have now begun to analyze additional samples from cell lines obtained from the Autism Genetic Resource Exchange and derived from children with autism. We believe that this analysis and potential detection of micro-chromosomal alterations will have significant implications in elucidating the etiology, the diagnosis, and biology of autism. P2.1.7 DETAILED PHENOTYPING AND GENOTYPING OF MULTIPLEX AND SIMPLEX FAMILIES WITH AUTISM SPECTRUM DISORDERS. J.J.A. Holden* and the Autism Spectrum Disorders Canadian-American Research Consortium. Dept. Psychiatry & Physiology, Queens University, Kingston, Ontario. ASD-CARC is a group of >60 researchers, clinicians, and parents, dedicated to “Unraveling the Mystery of Autism Spectrum Disorders”. Our hypothesis is that there are several different “autism syndromes”, with overlapping phenotypes, and that specific characteristics or gene findings will distinguish these groups. The objective of our Genetics Project is to recruit and assess 600 multiplex and 10,000 simplex families. This will enable subgrouping based on several criteria, including physical features and other characteristics, family history and characteristics in other family members. Most multiplex families will be assessed using the ADOS and ADI-R, whereas the majority of

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the simplex families will have diagnoses provided by clinicians and they will complete the PDDBI (parent and teacher versions also completed for the multiplex families). All families are invited to complete a variety of questionnaires relating to problems in the affected individual(s) and/or families members, including questionnaires on sleep, autoimmune disorders, obsessive compulsive behaviours and traits, handedness, language, personality, etc). In addition, some of the multiplex families are being assessed using a variety of laboratory-based tests: multimodal communication, eye-tracking, ERPs during emotion and word-recognition, etc. Samples for DNA studies are being collected from all consenting families and gene studies are carried out, first on the multiplex families, with promising results extended to the simplex families. Details about the studies being carried out and our progress to date will be presented. P2.1.8 EXAMINATION OF PARENT OF ORIGIN EFFECTS AT AUTISM SUSCEPTIBILITY LOCI ON CHROMOSOMES 2, 7 AND 15. J. Jaworski, A.E. Ashley-Koch, M. Cuccaro, J.R. Gilbert and M.A. Pericak-Vance*. Duke University Medical Center, Durham, NC 27710. Loci on chromosomes (Ch) 2, 7, and 15 have been implicated in susceptibility for autistic disorder (AD). To determine whether these loci display parent of origin (POO) effects, we examined 210 multiplex AD families ascertained through Duke or AGRE. ASPEX was used to test for excess paternal or maternal allele sharing among sibpairs. For Ch 2, D2S425 provided the most evidence for POO effects with a p-value of 0.03 for excess paternal sharing. For Ch 7, D7S640 provided the most evidence for POO effects with increased paternal sharing (p=0.01). For Ch15, D15S817 provided the most evidence of a POO effect with increased maternal sharing (p=0.02). GENEHUNTER-Imprinting was used to maximize the heterogeneity LOD score (hetlod) over five heterozygote penetrance models; dominant, co-dominant, recessive, paternal imprinting and maternal imprinting. For Ch 2, a peak 2pt hetlod of 1.8 was observed at D2S1776, maximizing under the maternal imprinting model. For Ch 7, the peak 2pt marker was D7S496, maximizing

under the dominant model (hetlod=1.1). For Ch 15, the maximum 2pt hetlod was observed with D15S817, under the paternal imprinting model (hetlod=0.87). While intriguing, these results do not provide definitive evidence for parent of origin effects in AD. It is likely that a much larger sample size will be needed for conclusive evidence to emerge for such complex inheritance patterns. P2.1.9 THE AUTISM GENETIC RESOURCE EXCHANGE: A NOVEL COLLABORATIVE RESOURCE FOR THE STUDY OF AUTISM GENETICS. C.M. Lajonchere*, S.J. Spence, T. Brown, T.C. Gilliam, P. Iversen, C.L. Martin and D. Geschwind. Cure Autism Now, Los Angeles, CA, 90036. Autism is the most heritable of neuropsychiatric disorders. The Autism Genetic Resource Exchange (AGRE) was created to establish a publicly available genebank with biomaterials, genotypic and phenotypic data from multiplex autism families to facilitate research into autism genetics. Established in 1998 by the Cure Autism Now Foundation, the resource consists of banked biomaterials (DNA, immortalized cell lines, serum) and a web accessible database that contains genotypic and phenotypic data available to approved researchers. Diagnosis is based on the Autism Diagnostic Interview-Revised (ADIR-R) supplemented by the ADOS-G, physical/neurological examination, detailed medical histories and psychometric testing. Genotyping and fine mapping have been performed by collaborating investigators at Columbia and UCLA, and subsequent genome scans will be performed at the Center for Inherited Disease Research. Fragile X testing and molecular cytogenetic studies have also been performed. To date, AGRE has biomaterial and diagnostic information for over 400 families (> 800 affected individuals), genotypic information for 350, and detailed phenotypic data (exams/histories/ADOS-G) for 180. A genomewide scan was conducted on 345 families in the AGRE collection in 2003. The AGRE program is a novel resource that successfully promotes collaborative efforts to speed the progress of autism genetic studies. Such large-scale open efforts are critical to

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the identification of genes for complex neurologic or psychiatric diseases. P2.1.10 INCREASED INCIDENCE OF MATERNAL HLA-DR4 IN SINGLE-BIRTH, BUT NOT MULTIPLEX FAMILIES WITH AUTISM . L-C. Lee, A. Zachary, S. Leffell, C. Newschaffer, K. Matteson, J. Tyler and A. Zimmerman. Johns Hopkins Univ. Sch of Public Health, Ctr for Autism & Developmental Disabilities Epidemiology, Sch of Med, & Kennedy Krieger Institute, Baltimore, MD 21205; Univ. of Tenn, Knoxville, TN 37920. Autoimmune disorders (ADs) occur with increased frequency in families with autism, particularly mothers. Since ADs are associated with specific antigens/alleles of the HLA system, we examined HLA in families to determine their incidence and parental inheritance. Two groups were studied: a sample of 18 families with one autistic child from East Tennessee (TN); and a sample from all areas of the USA, which included 33 families with multiple autistic children. The HLA-DR4 frequencies in the two groups were compared to 475 normal, unrelated Caucasians. Low resolution HLA typing indicated that DR4 was not higher in individuals with autism or in their fathers, compared to the normal controls. Mothers in the TN sample had significantly higher frequency of DR4 than normal controls (Odds Ratio=3.96; 95% CI= 1.39, 11.57). High resolution typing suggested no sharing of alleles, and no significant change in the distribution of DR4 alleles among those with DR4. No distortion in the segregation of the maternal DR4-bearing haplotype occurred among the autistic children. Distributions of HLA homozygotes and heterozygotes were normal and no evidence of antigen sharing between parents. Increased HLA-DR4 in mothers, but not children or fathers, in the single-birth families is consistent with a hypothesis that prenatal maternal-fetal immune interaction can affect fetal brain development in autism. This study was supported by the Autism Society of America - East Tennessee Chapter and by Barry and Renee Gordon.

P2.1.11 ORDERED-SUBSETS LINKAGE ANALYSIS ON SAVANT SKILLS OF AUTISTIC DISORDER IN 15Q11-Q13. D. Ma, J. Jaworski, M. Menold, S. Donnelly, R.K. Abramson, H.H. Wright, J.R. Gilbert, M.A. Pericak-Vance* and M. Cuccaro. Duke University Medical Center, Durham NC, 27710 Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to narrow potential regions of interest. Ordered-subset analysis (OSA) is a statistical method for identification of a homogeneous subset of families that contribute to overall linkage at a given chromosomal location as well as fine mapping and localization of susceptibility genes. Using OSA with insistence on sameness (IS) as a covariate, linkage has been demonstrated in chromosomal region 15q11-q13. Increased evidence for linkage has been shown in this same region using a stratified subgroup based on a savant skills factor (SSF) from the ADI-R. We examined the savant skills phenotypic finding in our sample of 91 multiplex autism families. Using Multipoint HLOD analysis with stratification by SSF with a cutoff point at 0.16 our families failed to demonstrate linkage to 15q11-q13 (p >0.05 for both recessive and dominant HLOD). In addition, using the SSF as a covariate in an OSA analysis also failed to show evidence for linkage (p = 0.74). Our findings do not support savant skills as an informative phenotypic subset for linkage in these data. These findings reflect potential differences in the samples as well as a disparity in the phenotypic meaningfulness of savant skills and insistence on sameness as covariates. P2.1.12 BUCCAL BRUSHING FOR DNA COLLECTION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. P. Manning-Courtney, C.A. Molloy, A.L. Morrow, G. Radloff and S.M. Davies. Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229. Autism Spectrum Disorder (ASD) is a complex genetic disease. Definitive genetic studies of the disorder require large sample sizes representative of children with ASD. The purpose of this study was to see if a minimally invasive technique using cytology

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brushes to collect buccal cell DNA would be tolerated by children with ASD. In a routine clinical setting, 20 of 21 families who were invited chose to participate in the study. A modification of the PUREGENE DNA extraction protocol produced a median DNA yield of 2.22 mcg from 4 brushes, a quantity sufficient for genotyping. No special preparation was required. The brush technique was well tolerated by all participants; nearly half (9/19) the parents described the technique as pleasant. Most respondents (13/19) did not think it was likely they would have participated if the study required a blood draw. The buccal brush technique is an effective, well tolerated method for obtaining genomic DNA in children with ASD. P2.1.13 INCREASED LIPID PEROXIDATION IN CHILDREN WITH AUTISM. X. Ming*, T.P. Stein, M. Brimacombe, T. Ticinetti, M.L.A. Daniels, W.G. Johnson and G. Lambert. The Autism Center, UMDNJ-New Jersey Medical School, Newark, NJ 07103 Autism is caused by the interaction of genetic and environmental factors. One of the best understood causes of autism is fetal exposure to thalidomide. Thalidomide has been shown to cause fetal malformation in rabbits by a mechanism involving oxidative stress. Sogut et al (2003) in a small scale clinical study of antioxidant enzymes showed that there is a reduction of glutathione peroxidase and catalase in autism. This study is designed to test the hypothesis that oxidative stress mechanism contributes to the pathogenesis of autism in the absence of thalidomide exposure. Urinary excretion of oxidative stress biomarkers, 8-hydroxy-2-deoxyguanosine (8-OHdG), 8 isoprostane F2a (8-iso-PGF2a) and creatine were determined in 33 children with autism and 29 healthy children. ELISAs were used to measure 8OHdG (Genox Inc., Baltimore MD) and 8-iso-PGF2a (Oxford Biomedical Research, Oxford, MI). Diagnosis of autism was made by ADI-R, ADOS or DSM IV criteria. The medication, vitamin, nutritional supplements and dietary history were recorded. 8-iso-PGF2a levels were significantly higher in children with autism as compared to healthy children (autism group: 32.92+/- 1.98 ng creat-1M, Control: 5.71+/-

0.98 ng creat-1M, p<0.01). There is also a trend of increased 8-OHdG urinary excretion in autism subjects, but it did not reach statistical significance possibly due to small number of subjects studied (autism: 13.73+/- 1.03 ng creat-1M, control: 11.87+/- 0.81 ng creat-1M, p=0.08). These results showed that lipid peroxidation is increased in this cohort of autism children who had no known exposure to thalidomide. P2.1.14 IDENTIFICATION OF POSSIBLE EPISTATIC GENES INVOLVED IN DEVELOPMENT OF AUTISM WITH FRAGILE X SYNDROME. S.T. Nowicki, L. Li, S. Jacquemont, J.P. Gregg, R.J. Hagerman, D.M. Rocke and P.J. Hagerman*. M.I.N.D. Institute, Departments of Pediatrics, Pathology, Biological Chemistry, School of Medicine, and Department of Applied Science, Division of Biostatistics, University of California, Davis, CA, 95616. Fragile X syndrome (FXS) is a single-gene disorder with a strong association with autism (AUT). FXS may hold clues to the identification of autism-associated genes. Our hypothesis is that one or more genes, from a pool of autism susceptibility genes, are responsible for the autism phenotype with FXS. To test this hypothesis, we analyzed the gene expression profile of fourteen patients (5 patients with FXS+AUT and 9 patients with FXS). A cognitive assessment and ADOS-G were performed. Total RNA was isolated from whole blood using Trizol. Samples were prepared and analyzed on the HG-U133A gene chip using standard protocols (Affymetrix). The data was transformed and normalized as described by Geller et al. A two-sample t-test was performed between the groups for each probe set associated with a subset of 520 genes previously described as autism susceptibility genes. A method proposed by Storey was employed that simultaneously controlled the false discovery rate (FDR) and maintained a high power. Using a controlled a level equal to 0.02, we detected 20 differentially expressed genes with an estimated FDR of 0.4 and p-values < 0.01. Several neurotransmitter receptors and transcripts involved in neuronal development were significantly up regulated in the FXS+AUT group compared to the

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FXS group. These data support our hypothesis that differential gene expression in FXS patients with autism offers additional clues to identify epistatic genes that contribute to the development of autism. P2.1.15 BEHAVIOR ANALYSIS OF SECRETIN RECEPTOR DEFICIENT MICE AS MODEL ANIMALS FOR AUTISM. I. Nishijima 1, T. Yamagata 4, C.M. Spencer 2, O. Alekseyenko 2, E. Weeber 3, J.D. Sweatt 3, M.Y. Momoi 4, R. Paylor 2, D.L. Nelson 2and A. Bradley 2. 1Department of Pediatrics, The Ohio State University, Columbus, OH 43205. 2Department of Molecular and Human Genetics, 3Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030. 4Department of Pediatrics, Jichi Medical School, Tochigi, Japan. Secretin is a peptide hormone that stimulates the pancreas to regulate digestion. The receptor for secretin is a G-protein coupled receptor, which is expressed in pancreas, muscle, kidney and brain. Recent reports indicated that treatment with exogenous secretin alleviated the symptons of autism in some patients. To analyze the mechanisms between secretin signaling and the development of autism, we made secretin receptor deficient mice. The mutant mice are normal and fertile; however, they have social behavioral abnormalities. Thus secretin signaling may be involved in one of the key cascades for normal neuronal development. We are continuing to analyze the effects of this mutation on the central nervous system. P2.1.16 MICROARRAY ANALYSES OF LYMPHOID CELLS FOR AUTISM SUSCEPTIBILITY GENES . R.K. Pullarkat*, D. Kowal, P.S. Pullarkat and M.A. Junaid. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 Autism is a multigene disorder with probable involvement of more than 10 genes. Extensive linkage analyses followed by positional cloning, so far failed to identify any major susceptibility genes for autism. The objective of the study is to explore

microarray analyses of lymphoid cells for the identification of autism susceptibility genes from families with multiple sibs affected. We have conducted microarray analyses of total RNA isolated from lymphoid cells from an autism family that included two affected boys, one affected girl, parents and an unrelated control. Analyses were carried out on Affymetrix HG-U133A gene chip. The image files were processed by Affymetrix Microarray Suite, and a list of genes showing more than two fold changes in expression were calculated. Candidate genes were selected by comparing aberrantly expressed genes with the genes in the areas of chromosomes that show significant linkages for autism. Compared to controls, less than 250 genes changed significantly in patients and parents. Some of the genes whose expressions are drastically reduced in autism patients are related to the immune response. Aberrant expressions of the genes were confirmed by quantitative real time PCR. Abnormalities in immune system have been implicated in autism although no specific gene defects have been consistently observed. Microarray on lymphoid cells is particularly suited to delineate aberration in the immune system. Supported by grants from NIH (NS40691), NAAR & New York State OMRDD. P2.1.17 DEVELOPMENT AND VALIDATION OF A CHROMOSOME 15 DNA MICROARRAY FOR COMPARATIVE GENOMIC HYBRIDIZATION AND APPLICATION TO AUTISM . T. Sahoo, W. Yu, C. Shaw and A. Beaudet. Baylor College of Medicine, Houston, TX. Array based comparative genomic hybridization (CGH) provides a high resolution genome-wide scan for identifying DNA copy number variations. We are developing a high density large-clone based DNA microarray for detection of abnormalities involving chromosome 15. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are known to map to 15q11-q13, a region which includes a 3-4 Mb domain subject to genomic imprinting. Paternal and maternal deletions of 15q11-q13 cause PWS and AS respectively. Cytogenetic abnormalities of chromosome 15q11-q13 cause autism. Interstitial duplications and isodicentric chr 15 found in

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association with autism are usually of maternal origin. An initial version of the chr15 microarray consisting of 120 genomic clones provides a genome scanning resolution of better than one clone per Mb on average across chromosome 15. The density of clones is extensive across the PWS/AS interval and previously identified regions of instability on chromosome 15. Inclusion of chromosome-specific subtelomeric clones across the genome will increase the detectability of unbalanced rearrangements. Initial validation of the proposed technology involves specificity and sensitivity of detection of cytogenetically identified 15q rearrangements in autistic disorder. A number of cases of autism with well characterized duplications involving 15q11-q13 serve as test samples for initial assessment. Continuing development of array CGH will help identify deletions, duplications, and unbalanced structural rearrangements contributing to autism and provide detailed data at the molecular level and provide a more cost-effective and sensitive approach to a molecular karyotype. P2.1.18 EFFECT OF MECP2 MUTATION ON EXPRESSION OF TWO CONDITIONALLY IMPRINTED GENES ON CHROMOSOME 15. R.C. Samaco, T.L. Simcox, A. Hogart, D. Braunschweig and J.M. LaSalle*. Med Micro and Immuno, Rowe Program in Human Genetics, School of Medicine, UC Davis, CA 95616 Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG binding protein 2 (MeCP2). Mutations in the coding region of MeCP2 have also been found at a low frequency in autistic and Angelman syndrome (AS) patients. Evidence of deficiencies in homologous pairing of 15q11-13 domains and in the percentage of MeCP2hi cells in RTT, autism and AS suggest an overlapping epigenetic pathway involving chromosome 15q11-13 and MeCP2 in the pathogenesis of these neurodevelopmental disorders. Although we previously determined that the parental expression of several imprinted genes was not affected by MECP2 mutation, we now examine two genes showing conditionally imprinted expression in brain. Allelic expression was determined in

(Mecp2tm1.1Bird/+ x PWK+/y)F1 brain tissue and no evidence for altered allelic expression was observed. In contrast, RNA-FISH and semi-quantitative RT-PCR amplification of Ube3a and Rasgrf1 showed preliminary evidence for expression level defects of these genes. Moreover, laser scanning cytometry (LSC) analysis of Rasgrf1 and Ube3a immunofluorescence in MeCP2-/y cerebral cortex samples confirmed differences in expression levels compared to wild-type controls. In addition, RTT patients display similar defects in protein expression, including one patient without a detectable MECP2 coding region mutation. These results further illuminate the role of MeCP2 in the pathogenesis of RTT and autism and provide evidence of potential downstream targets for MeCP2. P2.1.19 MECP2 EXPRESSION CHANGES DURING NEURONAL DIFFERENTIATION. Y.M. Rao and J.M. LaSalle*. Med. Micro. and Immuno., Rowe Pr. in Hum. Genet., UC Davis, CA 95616 Rett syndrome is an X-linked neurodevelopmental disorder caused due to mutations in MECP2, encoding methyl CpG-binding protein 2 (MeCP2). The disorder causes severe mental retardation and autistic behavior in females with a delayed age of onset, around 6-18 months. MeCP2 expression involves both transcriptional and post-transcriptional regulation, in which elevated MeCP2 expression is acquired in individual neurons during postnatal development. Two transcripts of 1.9 and 10 kb are observed for MECP2 due to alternative polyadenylation. We developed two cell culture models to investigate changes in MeCP2 expression. The human neuroblastoma cell line SH-SY5Ywas induced to differentiate with 16 nM PMA. Elevated MeCP2 expression was observed for 2 days following PMA treatment, prior to full differentiation at 3 days. Northern blots demonstrate a slight increase in both 1.9 kb and 10 kb transcripts by 6-24 hr following PMA treatment in SH-SY5Y cells, but not HEK control cells. The ratio of long to short MECP2 transcripts was higher in the SH-SY5Y cell compared to HEK. A second in vitro model utilized primary cortical neurons isolated from neonatal mice and induced to differentiate with

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retinoic acid (RA). Elevated MeCP2 expression was observed following 2-3 days in culture. The results demonstrate that elevated levels of MeCP2 expression can be induced by different neuronal cell culture methods and transient transcriptional changes of both MECP2 transcripts may explain the acquired elevated MeCP2 expression observed during postnatal brain development. P2.1.20 ANALYSIS OF EPIMUTATION IN THE 15q11-13 IMPRINTED DOMAIN IN AUTISM . M. Shinawi, R. Wagle, T. Sahoo, R.J. Schroer, R. Stevenson and A.L. Beaudet. Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas,USA. Greenwood Genetic Center, South Carolina 29646, USA The genome wide linkage studies have failed so far to identify major autism-related loci suggesting that many loci might contribute to the etiology of autism. We have proposed that there may be an epigenetic component to the etiology of autism. The maternally inherited duplication of 15q11-q13 among autistic patients indicates gene-dosage and parent-of-origin effects in this domain. In previous studies, we showed increased sharing for the paternal haplotypes at D15S817. One possible mechanism to explain this would be an imprint-switch failure in the maternally inherited paternal allele of the domain 15q11-q13. To determine the grandparental origin of this domain, we genotyped fathers from the AGRE and NIMH collections by analyzing a SNP within the telomeric portion of the imprinting center of the 15q11-q13 domain and analyzed the informative families by a combined RFLP/ methylation-specific PCR. In 29 families from the AGRE and NIMH collections, the paternal chromosome in the autistic child was derived from the paternal grandmother in 22 patients and paternal grandfather in 25 patients. This finding is not compatible with an imprint-switch failure, but it doesn’t exclude switch failure in the maternal germ line or a post-zygotic error. Currently, we are analyzing the grandpaternal of origin of the 15q11-q13 domain among informative mothers and families with a single autistic child from the South Carolina Autism Project with the hypothesis that the etiologic mechanisms may differ in families with

affected sib pairs compared to families with a single affected individual. P2.1.21 CHROMOSOME 7 BREAKPOINTS CORRESPOND TO LINKAGE PEAKS AND INDICATE CANDIDATE GENES FOR AUTISM SUSCEPTIBILITY. D.A. Skaar(1), L. Christ(2), M. Cuccaro(1), J.R. Gilbert(1), S. Schwartz(2) and M.A. Pericak-Vance*(1). (1)Center for Human Genetics, Duke University Medical Center, Durham, NC; 2) Dept. of Genetics, Case Western Reserve University, Cleveland, OH In a multiplex family ascertained for an autism linkage study, a paracentric inversion was found in one copy of Chromosome 7 ((inv(7)(q22-q31.2)) for the mother and all three children. Two of the children are autistic, and the third, while not diagnosed as autistic, exhibits expressive language disorder. Multiple researchers analyzing microsatellite markers have found linkage peaks to autism over the ~30cM region of 7q which includes this inversion, and around the probable breakpoints in particular. We report here the identification of the breakpoints, and investigations into association of the inversion with autism susceptibility. FISH mapping with BAC clones first identified a 194kb region for the proximal breakpoint, and a 175kb region for the distal. The proximal region contains a number of genes and pseudo-genes for Cytochrome P450 polypeptides (CYP3A5, CYP3A5P1, CYP3A7, CYP3A5P2, and CYP3A4) as well as the uncharacterized FLJ32468. The distal breakpoint region contains no known genes, but does contain several transcribed regions, indicated by ESTs, and one exon of a predicted novel gene. The precise breakpoints are being mapped by southern blotting, which will identify any directly affected genes. Also, SNPs are being tested in both breakpoint regions for linkage and association to autism, with the preliminary results suggesting significance. This work is funded by NINDS grant 2 P01 NS026630-16A1 P2.1.22 HOMOLOGOUS PAIRING OF 15Q11-13 IMPRINTED DOMAINS IN BRAIN IS

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DEVELOPMENTALLY REGULATED BUT DEFICIENT IN RETT AND AUTISM SAMPLES . K.N. Thatcher, D. Braunschweig, R.C. Samaco, J.M. LaSalle*. Medical Microbiology & Immunology, UC Davis Sch. Med., Davis, CA 95616. Mutations in MECP2, encoding methyl CpG binding protein 2, cause Rett syndrome (RTT), and a few cases of Angelman syndrome (AS) and autism. MeCP2 is predicted to be a transcriptional repressor of methylated genes, but its essential function appears limited to postnatal brain. We tested a potential role for MeCP2 in homologous pairing of imprinted 15q11-13 alleles in neuronal differentiation and brain tissue by fluorescence in situ hybridization (FISH). SH-SY5Y neuroblastoma cells showed a significant and specific increase in the percentage of chromosome 15q11-13 paired alleles following differentiation, coinciding with an increase in MeCP2 expression. Blocking MeCP2 binding to endogenous sites with a methylated decoy significantly lowered the percentage of paired alleles. FISH analysis performed on normal human cerebral samples on a tissue microarray demonstrated a significant increase in homologous pairing during early infancy that was specific to chromosome 15 and persisted throughout adulthood. Significant deficiencies in the percentage of paired chromosome 15 alleles were observed in RTT, AS, Prader-Willi (PWS), and autism brain samples compared to normal controls. We are currently expanding our studies to include additional autism samples, controls, and additional neurodevelopmental samples. These combined results suggest a role for MeCP2 in the nuclear organization of chromosomes in the developing human brain and demonstrate an association between several related neurodevelopmental disorders. Funded by MIND Institue and NIH. P2.1.23 A REVIEW OF CYTOGENETIC ABNORMALITIES IN AUTISM: IMPLICATIONS FOR GENETIC STUDIES. J.A.S. Vorstman, W.G. Staal, E. van Daalen and H. van Engeland. Department of Child and Adolescent Psychiatry Heidelberglaan 100 3584 CX Utrecht, The Netherlands

Despite the fact that genetic factors are strongly involved in autism, no specific genes have been identified consistently. Through linkage and association studies several loci have been connected with autism however, most results have been difficult to replicate. Alternatively, cytogenetic deficits associated with autism could be used to identify susceptibility genes and have been reviewed previously. Nevertheless, advances in genetic research and recent publications indicate the need for an extensive study of the literature. Therefore, the English-language literature was searched with the Pubmed and Medline libraries. All studies that related cytogenetical abnormalities with autism spectrum diagnosis were investigated and summarized. Next, the genes that mapped the relevant chromosomal abnormalities were identified using the available libraries of the human genome. The findings of this extensive review indicate that several specific chromosomal regions implicated in cytogenetic disorders, are associated with autism. Some candidate genes can be identified on the basis of their location on the breakpoints of a chromosomal rearrangement. Candidacy of other genes is suggested when they can be mutually connected on the basis of their positions in different cytogenetically or otherwise with autism associated regions (i.e. through association / linkage studies), while at the same time they are affiliated with the same neuro-biological pathway. We will present some of these putative candidate genes. Future directions: we are currently designing a multiprobe PCR based assay which we intent to use as a screening instrument for the detection of the most frequently reported cytogenetic abnormalities in autistic individuals. P2.1.24 RH AND ABO MATERNAL-FETAL INCOMPATIBILITY AND RISK OF AUTISM. P.P. Zandi, M.D. Fallin, D. Avramopoulos, Y. Huo and C.J. Newschaffer. Departments of Mental Health and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. Although evidence clearly suggests that genetic factors play an important role in autism, no autism-related genes have been conclusively identified. The limited success is likely due to the fact that the

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etiology of autism is complex and may involve non-Mendelian mechanisms of transmission. Rh and ABO maternal-fetal incompatibility may lead to an adverse prenatal environment with implications for fetal neuro-development. Two epidemiologic studies have implicated Rh and ABO incompatibility as risk factors for autism. However, these studies were of limited sample size and could not distinguish between associations that are due to the maternal-fetal incompatibility itself or to the presence of an autism susceptibility allele located close to either the maternal or fetal Rh or ABO loci. We are genotyping the Rh and ABO loci and neighboring microsatellite markers in a sample of [n = 370] autism trios (an affected proband and both biological parents) collected by the Autism Genetics Resource Exchange (AGRE). We will analyze the data using the maternal-fetal genotype incompatibility (MFG) test as adapted from the log-linear model for case-parent trios of Weinberg et al (1998) by Sinsheimer and colleagues (2003). The approach has recently proven successful in the study of Rh incompatibility and schizophrenia. We will present estimates of the effects for incompatibility at the Rh and ABO loci on autism risk separately from estimates of the direct effects of maternal and offspring genotype. This study is supported by CDC cooperative agreement U10/CCU320408-03 and a grant from the National Alliance for Autism Research. P2.1.25 BLOOD SEROTONIN AND YALE BROWN OBSESSIVE COMPULSIVE BEHAVIOR SCALE SCORES IN PARENTS OF PROBANDS WITH AUTISTIC DISORDER. H.H. Wright,* R.K. Abramson, A.V. Hall, S.A. Ravan, E.H. Cook and M. Cuccaro. Dept. Neuropsychiatry, Univ S Carolina Sch Med, Columbia, SC 29203 AD is a genetic neurodevelopmental disorder diagnosed in part by patterns of compulsive/stereotyped behaviors and rigidity. Abramson (2002) reported that a group of parents of individuals with AD have clinically significant Y-BOCS scores that correlate positively with the factor Insistence on Sameness derived from the Autism Diagnostic Interview - Revised (ADI-R)(Cuccaro,2002). Sutcliffe (2002) reported linkage and association of haplotypes at the 5HT transporter

locus in a group of individuals with AD with a rigid-compulsion factor derived from the ADI-R. Elevated blood 5HT is found in a subgroup of parents. This study examines the association between Y-BOCs scores and 5HT levels in parents. South Carolina parents (n=38) who had Y-BOCS scores and 5HT levels were identified from the Duke/Univ. of South Carolina study of 185 parents with 5HT levels. Seasonal variation in 5HT was not significant in the control sample. In parents there was no significant correlation between 5HT and Y-BOCS scores, but there was a significant negative correlation between 5HT and drugs (selective serotonin reuptake inhibitors-SSRIs, r=-0.462, p=0.004). A significant 5HT gender difference (male X=153.37±SE12.28, n=19; female X=103.74±SE17.23, n=19; t(1,36)=2.347, p=0.025) disappeared when SSRIs were included in the analysis (drug F=6.43 df=1, p=0.016; gender F=2.59 df=1, p=0.117). While an association between the 5HT system and Obsessive Compulsive Disorder has been reported, there is no significant correlation between blood 5HT and the YBOCS score in parents of individuals with AD in this preliminary study. Poster Session 2: Topic 2:` Epidemiology P2.2.1 BIRTH & FAMILY HISTORY RELATED RISK FACTORS IN A COHORT OF AUTISTIC PATIENTS. M. Brimacombe, M. Lamendola, A. Parikh, M.L.A. Daniels and X. Ming*. New Jersey Medical School, Newark NJ 07101-1709. An epidemiologic cohort study was conducted to identify specific birth & family history related risk factors associated with autism. The cohort consisted of one hundred and forty-four autistic patients referred to the Autism Clinic at the New Jersey Medical School over a two-year period. As part of patient intake, parents completed a detailed survey consisting partly of questions regarding family history, prenatal and birth history. This information was reviewed and clinical information validated by the supervising clinician. Frequencies of various birth and prenatal difficulties as well as the psychiatric, developmental and medical problems in

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the family were assessed and compared to national and New Jersey levels. Patients demonstrated high levels of psychiatric, developmental, and medical problems among family members. In regard to prenatal risk factors, significantly higher rates were found for the autism cohort versus reported national levels; prematurity (16.7% to 11.6%, P=.044), vaginal bleeding (16.7% to 6.6%, P=.001), prolonged labor (7.6% to .78%, P=.001), caesarian delivery (29.9% to 22.9%, P=.032), multiple delivery (9.7% to 3.1%, P=.001) and diabetes (6.3% to 2.9%, P=.025). Comparison with NJ rates were similar. These results support underlying genetic and environmental causes of autism and show lower levels of birth optimality in mothers of autistic children. P2.2.2 WISC PROFILES IN CHILDREN WITH AUTISM AND PDD . S. Chandler, T. Loucas, G. Baird, T. Charman and E. Simonoff, A. Pickles. School of Medicine and Biomedical Sciences, King’s College London, SE1 3SS. United Kingdom. Susie.Chandler@kcl.ac.uk Verbal and Performance IQ abilities were measured in a population-representative sample of children with autism (n=38) and PDD (n=74) who were able to complete the WISC-III (UK). Diagnoses were confirmed using the ADI-R, ADOS and clinical review. WISC data was analysed to examine the effect of IQ and diagnosis on learning ability profiles. There were no significant discrepancies between VIQ and PIQ for the high IQ (FSIQ>=70) or low IQ (FSIQ<70) group with autism (n=19, n=19, respectively), or for the high IQ or low IQ group with PDD (n=51, n=23, respectively). Differences between individual subtest standard scores and mean subtest standard scores were calculated in order to compare profiles across the 4 groups (autism and PDD, at high and low IQ). Only the low IQ group with autism showed the classic profile of stronger performance on perceptual organisation tasks (eg Block Design) compared to verbal comprehension tasks (eg Comprehension). There was a significant interaction between Diagnosis and IQ on Object Assembly (p<.05). When IQ<70, the autism group was stronger than the PDD group on this task but when IQ>=70 this pattern was reversed.

There was a main effect of IQ on Object Assembly and Coding (p<.001), with the high IQ groups showing more relative difficulty on these compared to the other subtests. There was also a significant effect of diagnosis on Block Design (p<.001), with the autism groups performing relatively well on this compared to the other subtests. These results do not indicate a uniform WISC profile across autism and PDD. Instead, patterns of learning ability appear to vary with diagnosis and IQ. Funder: Wellcome Trust P2.2.3 NEW JERSEY ANSWERS FOR AUTISM SURVEY. F. Desposito, W. Zahorodny and M. Brimacombe. New Jersey Medical School, Newark, NJ 07103. Many gaps exist in the scientific understanding of autism. The New Jersey Answers for Autism Survey (Survey) was established as a voluntary, comprehensive, longitudinal, autism-specific database. The goals of the Survey are to identify possible Autism Spectrum Disorders (ASD) risk and protective factors, characterize ASD subtypes, examine change in persons with autism, monitor needs of persons with ASD and their families. Participation in the Survey is limited to persons with ASD and parents of persons with ASD residing in New Jersey. Participation in the Survey is by completion of a questionnaire. The Survey recruits information related to demographic background, medical and developmental history and status, current functions and needs. This presentation will offer analysis of data provided by the initial 1,000 Survey participants. Information presented will describe the Survey methodology, define the Survey population, estimate risk factor associations, characterize phenotypic aspects of the population, report on treatments and interventions implemented on behalf of the Survey population. This research is supported by the New Jersey Governor's Council on Autism. P2.2.4 MERITS AND DEMERITS OF EARLY SCREENING FOR AUTISM SPECTRUM DISORDERS. C. Dietz, S.H.N. Willemsen-Swinkels, E. van Daalen, J.K. Buitelaar and H. van Engeland.

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UMC-Utrecht, Department of Child and Adolescent Psychiatry, Post box 85500, 3508 GA, Utrecht, The Netherlands. A two-stage protocolled screening for Autism Spectrum Disorders (ASD) was performed in a random population of 31.724 children at age 14 months. With this screening method, 19 children with ASD were identified. Although we demonstrated with this study that a very early detection of ASD is in fact possible, several limitations of early screening became as well apparent. The sensitivity of the instrument was not as high as we had hoped for. At least two reasons seem to be inherent to this problem. First, a high number of parents would not co-operate with our screening procedure. The hesitation of parents shows as well in the time span of 7 months on average between the home visit and the moment of diagnostic examinations, whereas no waiting list existed. Second, because developmental disorders like ASD will appear at some time in development, the age of screening is highly related to the sensitivity of the screening instrument. It is plausible to believe that especially the milder cases will be missed with a screening at this early age. The positive predictive value was lowered by the high amount of false positives. It should however be noted that no typically developing children were found within the screen-positive group but the instrument did depict children with related disorders like Language Disorder (n=20) and Mental Retardation (n=9). This questions the demarcation between the childhood psychiatric disorders, at least at this early age. Merits and demerits of especially early screening will be further discussed. P2.2.5 CHARACTERISTICS OF YOUTH WITH ASPERGER’S DISORDER REFERRED FOR PSYCHIATRIC SERVICES. D. Edgell*, R. Lampard and S.A. Johnson. Queen Alexandra Centre for Children’s Health, Child, Youth & Family Mental Health Services, Vancouver Island Health Authority, Victoria BC, V8N 1V7. In order to study the incidence and characteristics of Asperger’s Disorder in a sample of

youth referred to an inpatient-outpatient child and adolescent psychiatric facility we completed a retrospective review of clinical records for all individuals diagnosed with Asperger’s Disorder (ASP) between 1994 and 2000. Of the 1460 youths enrolled for services, 39 (2.7%) received a diagnosis of an autism spectrum disorder based on DSM-IV criteria, and 22 (1.5%) were diagnosed with ASP. All of those diagnosed with ASP were male. Within the ASP group, the initial assessment and/or intervention for symptoms related to the disorder was completed at a mean age of 5.6 years. However, the mean age for diagnosis of ASP was 11.3 years. The most frequent previous diagnoses were Attention Deficit Hyperactivity Disorder (59 % of ASP group) and developmental disability (23% of ASP group). The majority of youth had current comorbid psychiatric diagnoses, were receiving psychotropic medication, were involved in special education services, and took part in outpatient psychiatric services. Youth with ASP referred for psychiatric support had complex developmental and psychiatric backgrounds. In most cases, these children and their families required significant mental health and educational support services, usually extending over many years. This research was supported by a grant from the Queen Alexandra Foundation for Children. P2.2.6 AUTISM PREVALENCE BY BIRTH COHORT FROM US SPECIAL EDUCATION DATA . M.D. Falb, J.G. Gurney* and C.J. Newschaffer. Center for Autism and Developmental Disabilities Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; *Univ. of MN, Minneapolis, MN 55455. National data collected by the US Department of Education’s Office of Special Education Programs on children receiving special education services were analyzed by birth cohort for prevalences of autism and three other special education classifications (hearing impairment, speech/language impairment, and other health impairments). Age-specific prevalences were calculated for these special education classifications for annual birth cohorts from 1975 to 1998 using denominators from US Census Bureau estimates.

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For autism, there are clear birth cohort differences - prevalence is increasing with successive (younger) birth cohorts. This effect is greatest for cohorts born between 1987 and 1992. For cohorts born after 1992, the prevalence increases with each successive year but does not appear to be as great as in previous years, although there are fewer data points available within cohorts. The curves for other health impairment are notable both because this is the special education typically including children with attention deficit hyperactivity disorder and because strong cohort differences are also present here. There are no birth cohort differences for speech language impairment or hearing impairment prevalence. Cohort graphs reveal that autism prevalence is increasing with time, as evidenced by higher prevalence in younger birth cohorts. Whether the narrowing in vertical separation of the cohort curves marks a slowing autism prevalence increases remains to be seen. This study was supported by CDC cooperative agreement U10/CCU320408-03. P2.2.7 EPIDEMIOLOGY OF AUTISM AMONG CALIFORNIA-BORN TWINS. J.K. Grether*, M. Anderson, B. Hopkins, L.A. Croen, P. Choate and R. Huff. California Department of Health Services, Oakland, CA 94612 The epidemiology of autism among twins is largely unknown. From among the autism population enrolled with the California Department of Developmental Services (DDS), we have identified >400 twin pairs born 1987-1998 in which one or both members of the pair are diagnosed with autism. The electronic client records on these twins have been individually linked to their birth certificate to identify births to California residents and to obtain demographic variables. To describe and interpret the epidemiologic characteristics of these twins with autism, we have constructed multiple comparison groups: twin pairs enrolled in DDS with mental retardation of unknown etiology without autism (N=719), all live born twins (N=140,656), all twin pairs/pregnancies (N=70,328), and all live born singletons (NH6,000,000). Variables considered include maternal and paternal age, education, and

race; infant gender, birth weight, and birth order; length of interval since last live birth; parity; and twin concordance in DDS for autism. The large number of twins in this population-based series permits an evaluation of the epidemiology of autism among twins with a high level of precision. Univariate and multivariate data will be presented from the most informative comparisons to evaluate possible etiologic clues. P2.2.8 CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT. R.L. Hansen*, I. Hertz-Picciotto, L.A. Croen, M. Sigman, G.G. Hughes, A. Harley, C. Beck and A. French. M.I.N.D. Institute, UCDavis, Sacramento, CA; and UCLA, Los Angeles, CA; CHARGE is a case-control epidemiologic study of the Center for Children’s Environmental Health at UCDavis to study the contributions of genetic susceptibility and environmental exposures to the development of autism and other developmental disabilities. CHARGE will compare 2000 children 2-5 years of age born in CA with autism, developmental disabilities and typical development on exposures to environmental factors posited to be developmental neurotoxins, susceptibility factors that may affect early brain development such as gene expression, immune system and metabolic function, and clinical phenotype. Recruitment of children with autism and developmental disability has required the establishment of collaborative protocols with 7 regional centers in CA, and the development of a protocol for identifying/recruiting typically developing children from the general population using a state-wide birth certificate database. Community outreach and education, supported by a parent-provider based community advisory council, has been critical. Evaluations include parent interview regarding demographic /lifestyle factors and exposure history during pre-conception, prenatal and postnatal periods; clinical evaluation of children including cognitive, behavioral and medical assessment; collection of biological specimens; medical record review including obstetric, neonatal, pediatric and dental records; parent questionnaires regarding behavioral history. Critical features of the recruitment process and protocols will be presented, including

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difficulties and successes in their implementation. Current recruitment/evaluation data will also be presented. P2.2.9 WHY SEARCH FOR ENVIRONMENTAL FACTORS IN AUTISM? I. Hertz-Picciotto, L.A. Croen and R.L. Hansen. M.I.N.D. Institute and Departments of Epidemiology and Preventive Medicine, and of Pediatrics, University of California Davis; Kaiser Permanente Division of Research . This paper reviews the rationale for examining environmental factors as causes of and contributors to autism. First, the literature on twin concordance and familial recurrence is examined critically. In particular, it is useful to focus on differences in phenotypic expression (e.g., severity), noting that monozygotic twins who are at different points along the autistic spectrum provide evidence of non-genetic contributions to the condition. Similarly, the familial recurrence rates are assessed with regard to diagnostic classification. Second, the strength of the literature on chemical and biological agents that have been reported to have an association with increased risk of autism is assessed. As recent work in experimental animals suggests that viral exposures can induce autistic-like behaviors, the rubella experience in relation to autism is scrutinized carefully. Third, the role of prenatal neurotoxin exposures in cognitive and social development is discussed, with a focus on mercury and polychlorinated biphenyls. Fourth, if incidence has been rising over the last few decades, then this constitutes a further argument for the study of non-genetic causes. Finally, beyond the empirical evidence, it is argued that the coherence of any hypothesized behavioral intervention paradigm presumes neural plasticity in some form, beyond the period of any hypothesized insult, whether genetic or environmental in origin. Thus, environmental factors, broadly defined, would be expected to contribute to autism, whether or not the incidence of the disorder is increasing. P2.2.10 MEDICAID EXPENDITURES FOR CHILDREN WITH AUTISM: 1994 THROUGH 1999 . R.F. Ittenbach, J. Cao, D. S. Mandell, S. E. Levy, J.

Pinto-Martin*. University of Pennsylvania CADDRE, School of Nursing, The University of Pennsylvania, Philadelphia, PA 19104. Recent studies have reported an increase in the number of children with autism. Such reports imply a corresponding increase in medical expenses for the service delivery system. The purpose of the present study was twofold: first, to estimate Medicaid expenditures associated with a diagnosis of autism for a sample of Pennsylvania children 0 through 21 years of age (n = 298) for the years 1994 through 1999; and, second, to compare these expenditures to those of other Medicaid-eligible children without autism from the same county during the same time period. Results suggest that children diagnosed with autism had Medicaid reimbursed expenditures that were approximately ten times greater than those of other Medicaid-eligible children. Although average annual expenditures for the two groups remained relatively similar in ambulatory physical care and emergency physical care, average annual expenditures varied markedly in other areas such as inpatient physical health care. Major cost differences were observed in outpatient mental health care, as expenditures for children with autism decreased over the six-year period from $4,100 (1994) to $2,632 (1999), yet increased for other children, $58 (1994) to $114 (1999). Average inpatient mental health expenditures over the same time period followed a less discernable pattern. While the number of children with autism served each year in the Medicaid system remained relatively stable during this period, per person expenditures actually decreased, phenomena that were believed attributable to decreases in average outpatient and inpatient mental health expenditures. P2.2.11 CHARACTERISTICS OF CHILDREN WITH AUTISTIC SPECTRUM DISORDERS SERVED IN COMMUNITY MENTAL HEALTH SETTINGS, AND CORRELATES OF PHYSICAL AND SEXUAL ABUSE . D.S. Mandell*, C.M. Walrath, B. Manteuffel, G. Sgro, J.A. Pinto-Martin and PA-CADDRE. University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

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We describe the characteristics of children with autistic spectrum disorders (ASD) receiving treatment in community mental health settings, and examine the prevalence and correlates of physical and sexual abuse within this group. Children who had received a primary diagnosis of ASD in a national community mental health intitiative were compared with children with other diagnoses on socio-demographic and psychosocial characteristics, presenting problems and service histories. Regardless of diagnosis, children were most often referred because of disruptive behaviors. Children with ASD were more likely than other children to be referred for social interaction difficulties and strange behavior than children with other diagnoses. Within the group of children diagnosed with autism, caregivers reported that 18.5% had been physically abused and 16.6% had been sexually abused. Physically abuse was significantly associated with sexual acting out, and conduct-related and academic problems. Sexual abuse was significantly associated with sexual acting out, suicide-related, or self-injurious behavior. After adjusting for other factors, the relationship between sexual abuse and sexual acting out persisted; the relationships between suicide-related behavior and sexual abuse, and between conduct-related problems and physical abuse remained of marginal significance. Based on the prevalence of abuse in this group of children, clinicians should be as attuned to the psychosocial histories of children with autism as they are for other children. P2.2.12 INVESTIGATING DEVELOPMENTAL DELAYS STUDY: COMPARISON OF SCQ AND PDDST. C.J. Newschaffer, L-C. Lee, A. B. David and N. L. Lee. Center for Autism and Developmental Disabilities Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. OBJECTIVE: To compare the effectiveness of the Social Communication Questionnaire (SCQ) and the Pervasive Developmental Disorders Screening Test (PDDST) in identifying autism spectrum disorder (ASD) among children age 3-5 years receiving special education services. METHODS: A brief, self-administered questionnaire consisting of demographic questions

and the SCQ and PDDST was mailed to all parents of children age 3-5 years receiving special education services through the Howard County School District in Maryland (n=740). In these preliminary findings, parent’s report of the child having an autism special education classification determined case status. Clinical assessments using the ADOS and ADI-R will validate these administrative classifications and the results will be presented at the meeting. RESULTS: Thirty-five percent (n=258) returned completed surveys, and 15% of these (n=38) scored positive for ASD on either the SCQ (score >15) or PDDST (score >13). When compared to autism special education classification, the sensitivity and specificity of the SCQ was 55.2% and 90.8%, respectively, with a positive predictive value (PPV) of 43.2% and a negative predictive value (NPV) of 94.1%. The sensitivity and specificity of the PDDST were 20.7% and 98.7%, respectively (PPV 66.7% and NPV 90.8%). CONCLUSION: Sensitivity of these two brief screening tools appears limited. While specificity is higher, PPV is still fairly low even in this target population with enriched autism prevalence. This study is supported by CDC cooperative agreement U10/CCU320408-03. P2.2.13 ENVIRONMENTAL TOXINS AND DEVELOPMENTAL DISORDERS: A U.S. ECOLOGICAL STUDY. R. Palmer*. University of Texas Health Science Center San Antonio, Dept of Family and Community Medicine, San Antonio Texas, 78232 Objective: To investigate the association between state level environmental toxins and rates of childhood developmental disorders. Methods: Data from the U.S. dept of Education and the Environmental Protection Agency were analyzed using poisson regression models to estimate the relative rate of developmental disorder associated with environmental neurotoxins including mercury and lead. Results: Adjusted for population size and economic factors, there was a significant increase in a variety of developmental disorders associated with increased levels of environmental toxins. Compared to states in the lowest quintile of environmental

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toxins, states in the highest quintile were approximately three times more likely to have increased rates of mental retardation, learning disabilities, autism and neurosensory impairments. Conclusions: This ecological study indicates a state level association between rates of developmental disorders and the number of pounds of recognized developmental toxins that are put into the environment. This association warrants further investigation and has important policy implications. P2.2.14 AUTISM IN CALIFORNIA: EPIDEMIC OR ILLUSION? D. Pyles. Dept. of Education, CSU Dominguez Hills, Carson, CA 90747 As a means of resolving apparent discrepancies in reported prevalence of autism in the State of California ArcView GIS software was employed to create a comprehensive map displaying figures provided by the California Regional Centers. The twenty-one regional centers within the State of California provide a coordinated system for diagnosing individuals suspected of or having a developmental disability. Maps were created displaying the changing occurrence rates of autism in the State of California over the last 10 years as it pertained to the twenty-one regional centers. The study concluded that there needs to be further employment of ArcView GIS software in tracking the prevalence of autism in the State of California, which warrants serious attention by the educational, scientific and medical communities. P2.2.15 POPULATION-BASED MONITORING OF THE AUTISM SPECTRUM DISORDERS VIA RECORD REVIEW: OPERATIONALIZING THE DSM-IV TR CRITERIA. C. Rice*1, G. McGee 2, M. Morrier 2, C. Lord 3, J Baio 1 and L. Wiggins 1. 1Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-86, Atlanta, GA 30333; 2Emory University; 3University of Michigan. In order to determine prevalence rates and establish ongoing monitoring of the Autism Spectrum Disorders (ASDs), the Centers for Disease Control and Prevention (CDC) has developed a

record review methodology to identify children with an ASD in the population. Over time, data from these surveillance systems will enable a more comprehensive understanding of trends in rates and risk factors associated with the ASDs. The initial prevalence study was conducted in five counties of metropolitan Atlanta for children ages 3-10 years in 1996 (N = 290,000) and 3.4 per 1,000 children were identified as having autism (a minimal estimate of the ASDs including Autistic Disorder, Asperger’s Disorder, and Pervasive Developmental Disorder-Not Otherwise Specified). CDC has now funded a collaborative network of 16 sites in 18 states with 14 of these sites using a similar methodology to determine ASD prevalence. Current data collection is underway for 8 year old children residing in the study areas during the years 2000 and 2002 identified through a systematic review of evaluation records at multiple sources, e.g., schools, clinics, evaluation centers. A panel of clinicians and researchers developed a systematic coding scheme updated to reflect the DSM IV, Text Revision to each individual record. This presentation will discuss the development of the use of the DSM-IV TR criteria to establish a coding scheme and reliability standards for determining surveillance case status through population-based record review. P2.2.16 ARE CHILDREN WITH AUTISM MORE LIKELY TO REPORT ALLERGIC DISORDERS COMPARED TO HEALTHY CONTROLS? T. Webb*, J. Meinzen-Derr, S. Wilson and M. Wess. University of Cincinnati, Cincinnati, OH 45267 Our objective was to determine the prevalence of allergic disorders in children identified with autism compared to healthy controls. Subjects (ages 3-17 years) were participants of the National Health Interview Survey between 1997-2001. Autism was defined as a healthcare provider diagnosis of autism as reported by the interviewee. Allergies were self-reported by the interviewee. We conducted a series of multi-variable logistic regression models using SAS-callable SUDAAN to investigate the relationship of autism with respiratory, digestive, and skin allergies in children after controlling for developmental delay, chronic illness, asthma history, chronic medication use, frequency of physician

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visits, family size, age, and sex. Children with autism were more likely to have reported digestive and food allergies (OR 2.92, 95% CI 1.72 - 4.96) when compared to healthy controls. There was a trend towards a positive association of autism and respiratory allergies (OR 1.23; 95%CI 0.79-1.90) and skin allergies (OR 1.40; 95% CI 0.81-2.41), which did not reach statistical significance. However, children with autism were significantly less likely to report a history of asthma (OR 0.35; 95% CI 0.19-0.66). In conclusion, children with autism were reported to have an increased prevalence of allergic disorders, particularly of the gastrointestinal system, and less likely to report asthma. Further research to examine the link of autism and immunologic disorders, including allergic diseases, is warranted. P2.2.17 A COLLABORATIVE NETWORK FOR MONITORING THE AUTISM SPECTRUM DISORDERS IN THE UNITED STATES. J. Wojcik* and ADDM CADDRE Network. CDC, 1600 Clifton Road, MS E-86, Atlanta, GA 30333. Given concerns about increasing rates of children with an Autism Spectrum Disorder (ASD), the Centers for Disease Control and Prevention (CDC) has recently established a collaborative effort to monitor rates of the ASDs in the US. Recent estimates of ASD prevalence are as high as 2-6 per 1,000 and service providers have reported notable increases in the number of people with ASDs receiving services. In order to determine prevalence rates in areas across the US and establish ongoing monitoring of ASDs using a population-based methodology, CDC has funded an alliance of researchers organized as the Autism and Developmental Disabilities Monitoring (ADDM) Network and the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE). The ADDM CADDRE Network consists of 16 sites in 18 states. The Network has established common case definitions and methods for case abstraction, review, and quality assurance. Children with an ASD are currently being identified from a combined population base of over 600,000 eight year old children who were residing in the study areas in either the years 2000 or 2002. These data will

provide initial information for the establishment of an ongoing monitoring system for ASDs, including diagnostic information, behavioral descriptions, and associated conditions. This poster will present the network’s methodology for case identification, abstraction, and determination of case status and results to date. Over time, data from the Network will provide a comprehensive understanding of trends in rates of ASDs and provide an important resource for further research on risk factors associated with the ASDs. P2.2.18 EARLY HEAD GROWTH IN AUTISM. C.K. Yoshida*, L.A. Croen, R. Odouli, M. Wier, R.L. Hansen, J.K. Grether and K.B. Nelson. Kaiser Permanente Division of Research, Oakland, CA, 94612. We examined serial measurements of head circumference (HC) to explore whether HC between birth and one year of age differed between children with autism and typically developing children (controls). All children with autism (n=23) and controls (n=25) were singleton, non-Hispanic white, male, term infants born at a Kaiser Permanente Northern California (KPNC) facility in 1994 who remained health plan members for at least 2 years following birth. All anthropometric measurements recorded in the first year of life (head circumference, weight, length/height) and dates of measurements were abstracted from birth hospitalization and pediatric outpatient charts. Autism diagnoses were verified by expert clinical review of detailed diagnostic and clinical information abstracted from KPNC medical records. We compared the mean HC of children with autism and controls at birth, 2 months, 4 months, 6 months, and 12 months of age for the subset of children with measurement data at each of these time points (11 cases, 12 controls). No case-control differences in unadjusted or weight- and height-adjusted mean HC were observed at any age (adjusted means at birth: 35.7 vs. 35.5, p=0.7; 2mos: 40.5 vs. 39.8, p=0.1; 4mos: 43.6 vs. 43.2, p=0.5; 6mos: 45.5 vs. 44.9, p=0.4; 12mos: 48.0 vs. 48.2, p=0.7). These findings suggest that factors not controlled for in previous studies may have resulted in spurious case-control differences in head circumference.

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P2.2.19 NEW JERSEY ANSWERS FOR AUTISM SURVEY. M. Brimacombe, W. Zahorodny and F. Desposito. New Jersey Medical School, Newark, NJ 07103. Many gaps exist in the scientific understanding of autism. The New Jersey Answers for Autism Survey (Survey) was established as a voluntary, comprehensive, longitudinal, autism-specific database. The goals of the Survey are to identify possible Autism Spectrum Disorders (ASD) risk and protective factors, characterize ASD subtypes, examine change in persons with autism, monitor needs of persons with ASD and their families. Participation in the Survey is limited to persons with ASD and parents of persons with ASD residing in New Jersey. Participation in the Survey is by completion of a questionnaire. The Survey recruits information related to demographic background, medical and developmental history and status, current functions and needs. This presentation will offer analysis of data provided by the initial 1,000 Survey participants. Information presented will describe the Survey methodology, define the Survey population, estimate risk factor associations, characterize phenotypic aspects of the population, report on treatments and interventions implemented on behalf of the Survey population. This project is supported by the New Jersey Governor's Council on Autism. Poster Session 2: Topic 3: Structural Brain

Imaging P2.3.1 MRI VOLUMETRIC ANALYSES OF THE MEDIAL TEMPORAL LOBE IN AUTISM AND ASPERGER SYNDROME. C.M. Schumann*, J. Hamstra, B.L. Goodlin-Jones, M.H. Buonocore, C.R. Lammers and D.G. Amaral. The M.I.N.D. Institute, UC Davis, Sacramento, CA 95817. We initiated a series of magnetic resonance imaging (MRI) studies designed to better define brain alterations associated with autistic spectrum disorders. Here we report findings on the amygdala and hippocampus. Neuroanatomical borders were defined and volumetric measurements recorded

from T1-weighted 3D SPGR images of male subjects 7-19 years of age in four diagnostic groups: autism with mental retardation (IQ < 70; n=18), autism without mental retardation (IQ >70; n=15), Asperger syndrome (IQ >70; n=15), and age-matched typically-developing controls (IQ >70; n=14). Children 7-12 years of age with autism, with and without mental retardation, had a larger right amygdala relative to typically-developing children. In addition, young children with autism without mental retardation had a larger left amygdala volume relative to typically-developing children. Through adolescence, the size of the amygdala increased with age in typically-developing children, but not in children with autism. At 12.5-19 years of age, there was no difference between groups in amygdala volume. Hippocampal volume did not change with age in typically-developing children, and was larger in children with autism plus mental retardation relative to typically-developing children and those with Asperger syndrome. These data indicate an abnormal pattern of medial temporal lobe development in autism that persists through adolescence and varies by autism spectrum diagnosis. Funded by The M.I.N.D. Institute and the NIMH. P2.3.2 SUPERIOR TEMPORAL GYRUS ABNORMALITIES IN CHILDREN WITH AUTISM. A.Y. Hardan*, M. Vitale, S. Muddasani, M.S. Keshavan and N. Minshew. Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA 15213. Structural abnormalities have been reported in several brain regions in children and adults with autism. While multiple studies have examined the volume of the total brain, the amygdala, and other regions of interest, the superior temporal gyrus (STG), a structure that has repeatedly been incriminated in the pathophysiology of autism, has received little attention. The volume of the STG was measured on MRI scans obtained from a sample of 40 non-mentally retarded individuals with autism and 40 gender, IQ, and age group-matched healthy controls. When controlling for total brain volume, the size of the total left and the right posterior STG were found to be larger in children with autism (d 12 years

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of age) when compared to matched controls. No differences between the two groups were observed in any region in the adolescent and adult groups. The STG plays an important role in social cognition and in language development, and the abnormalities reported in the present investigation may shed light on the deficits reported in these two domains in autism. Additionally, the age-related aspects of these anomalies should provide impetus to examine the developmental characteristics of on any abnormalities observed in this severe disorder. This work was supported by grant MH 64027 to Dr. Hardan and NS 33355 and 35469 to Dr. Minshew. P2.3.3 BRAIN VOLUMES IN BIOLOGICAL NON-AFFECTED PARENTS OF AUTISTIC PROBANDS. S. Palmen 1, H. Hulshoff Pol 2, C. Kemner 1, H. Schnack 2, R. Kahn 2 and H. van Engeland 1. Departments of Child and Adolescent Psychiatry1 and Psychiatry2, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. Objective: Autism is a neurodevelopmental disorder with a genetic origin of 90%. Likewise, brain volume has a genetic origin of 90%. Previous studies by our group have reported a 5% increase in brain volume in autistic children and adolescents. As it has never been established whether brain volumes of biological non-affected parents of autistic probands are enlarged as well, quantitative anatomic brain magnetic resonance images of the biological non-affected parents of these autistic probands were compared with those of healthy control couples. Identifying structural brain abnormalities under genetic control is of particular importance as these could represent endophenotypes of autism. Methods: Brain volumes were measured in 29 autism parent couples and 30 healthy, matched control couples. Results: No significant differences were found between the autism parent couples and the healthy control couples in any of the brain volumes (intracranial, total brain, frontal, parietal, temporal, and occipital lobe, cerebral and cortical gray and white matter, cerebellum, lateral and third ventricle volume). No significant effect of gender was found.

Conclusions: Biological, non-affected parents of autistic probands do not show brain enlargement. Thus, it seems that increased brain volume is not part of the genetic diathesis of autism. More likely, the increased brain volume found in autistic probands may represent a secondary, likely non-inherited, factor which, combined with genetic risk for autism, increases the chances that an individual will manifest the disorder. P2.3.4 REPETITIVE BEHAVIOR IN AUTISM SPECTRUM DISORDER: THE RELATIONSHIP BETWEEN BRAIN AND BEHAVIOR. K. Dominick, R. Killiany, G.J. Harris and H. Tager-Flusberg*. Lab of Developmental Cognitive Neuroscience, Boston Univ. School of Med., Boston, MA 02118. This research explores autism-specific neuroanatomic abnormalities and their relationship to one of the core domains of autism, the restricted behavior domain (RB). Two studies were conducted in order to (1) characterize repetitive behaviors in children with autism spectrum disorder and (2) to investigate putative neural substrates of such behavior. In the first study, participants were children with autism spectrum disorder (ASD) and children with a history of language impairment (HLI). The Repetitive Behavior Scale - Revised was used to characterize restricted repetitive behaviors in these children (Bodfish, Symons & Lewis, 1999; Bodfish et. al. 2000). In the second study another cohort of children was used in magnetic resonance imaging (MRI) analyses. Coronal 3D-SPGR, T1-weighted scans were obtained from 20 children with ASD and HLI. Two regions of interest were defined: the anterior cingulate gyrus and the caudate nucleus. Regions of interest were measured using the software package “3D Slicer” (www.slicer.org) while blind to both patient diagnosis and identity. The findings implicate the anterior cingulate gyrus and the caudate nucleus as substrates of repetitive behaviors and offer insight into specific brain-behavior relationships in autism. The results are discussed in terms of neural abnormalities seen in children with autism and the role played by individual differences in restricted repetitive behaviors. Funded by a grant from NIDCD: U19 DC 03610.

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P2.3.5 BRAIN GROWTH DIFFERENCES IN AUTISM FROM BIRTH TO 46 YEARS: A META-ANALYSIS. E. Redcay* 1 and E. Courchesne 2. Departments of Psychology1, Neurosciences2, UCSD, San Diego, CA 92037. Brain size abnormalities are commonly reported in autistic individuals; however, the developmental course of this overgrowth is often overlooked. A recent finding suggests early brain development in autism is characterized by a period of rapidly accelerated brain growth (Courchesne et al., 2003). To examine brain growth rates across a wider age range, brain size measures from 12 MRI and 2 head circumference studies, which together covered the ages from birth to 46 years, were analyzed. Due to the variability in MRI acquisition and segmentation methods, percent differences (%Diff) between autistic and control participants were calculated within each study (100*(Autistic-Control)/Control). %Diff values were plotted against mean age and a curve fitting algorithm was used to estimate a continuous function. While the autistic brain is smaller than normal by an average of -8% at birth, the average %Diff across 0.5 to 4 years is +10%. Brain growth slows during late childhood, such that the average %Diff is only +2.66% between ages 5 and 12. During adolescence and adulthood, the size of the autistic brain is near normal, with an average %Diff of +1.62%. These findings suggest the greatest differences in brain growth occur just prior to, and during, the clinical behavioral onset of autism. Understanding the neurobiological causes and consequences of this transient, massive overgrowth may give insight into the etiology of autism. (Supported by RO1NS-19855) P2.3.6 TRANSVERSE RELAXATION TIME ABNORMALITIES OF FRONTAL-SUBCORTICAL CIRCUITS IN AUTISM. J. Hendry, T. DeVito, N. Gelman, N. Rajakumar, P. Williamson, W. Pavlosky, D.J. Drost and R. Nicolson. University of Western Ontario, London, Ontario, Canada Objectives: Although abnormalities have been noted in neuroimaging studies of autism, few have specifically examined MRI transverse relaxation

times (T2). The purpose of this study was to examine T2 for regions involved in frontal-subcortical circuits in males with autism. Methods: Fourteen males with autism (age: 8.9±2.9 years) and 16 male controls (age: 10.1±2.6 years) participated in this study. Patients all had a non-verbal intelligence greater than 70. All controls were screened using the K-SADS to exclude psychiatric disorders. The groups did not differ significantly in age, sex, race, or non-verbal intelligence, although more patients than controls were not right-handed (4/14 vs 0/16). All subjects completed a magnetic resonance scan using a 3T MRI scanner. T2 images were acquired using a GESFIDE sequence. T2 from the basal ganglia (caudate nucleus, putamen, globus pallidus), thalamus, and frontal white matter was analyzed using a slice parallel to the imaginary line joining the anterior and posterior commissures. Group differences in T2 were compared using one-way ANOVA. Results: Patients with autism had increased T2 in the left frontal white matter (p=0.03), left putamen (p=0.05), and left thalamus (p=0.05). There were also significant differences in asymmetry, with patients having a reversal of the pattern seen in controls in the frontal white matter (p=0.02) and in the globus pallidus (p=0.04). Conclusions: Patients with autism had significant increases in T2 relaxation times in several left-sided regions, suggesting abnormalities of tissue composition in frontal-subcortical circuits, particularly in the left hemisphere. P2.3.7 MRI-BASED PARCELLATION OF THE CEREBELLUM IN AUTISM AND SLI. S.M. Hodge, N. Makris, G.J. Harris*, L. McGrath, S. Steele, D.N. Kennedy, V.S. Caviness Jr., J. Frazier and H. Tager-Flusberg. Mass. General Hospital, Charlestown, MA 02114 and Boston University School of Medicine, Boston, MA 02118. We report a structural imaging study of the cerebellum in autism and specific language impairment (SLI). The cerebellum was subdivided at a level of analysis that matches the current understanding of anatomy and with a method that conserves the topographic uniqueness of the individual brain. Coronal 3D-SPGR T1-weighted scans were obtained from 42 boys 6-13yrs: 22 with

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autism (16 with language impairment, 6 with normal language ability), 9 with history or present SLI, and 11 normal controls. We applied a system for parcellation of the cerebellar cortex into well-defined closed areas, or parcellation units (PUs) based upon a set of fissures (see Schmahmann, 2000, and Makris, 2003). Cerebellar cortical exterior and gray-white matter borders were defined, 11 fissures were identified using a cross-referential morphometric tool, and cerebellar subdivision was performed. The entire cortex was parcellated into 23 PUs for each hemicerebellum: 11 in each hemisphere and 12 in each hemivermis. Preliminary results for 5 boys with autism and language impairment, and 5 boys with SLI showed no group distinction in the PU volumes of the vermis or hemisphere. Total cerebellum volume was larger, but not significantly, in the autism group. Support: NIDCD: PO1 DC 03610, part of the CPEA; and NIMH: K08 MH01573-01. P2.3.8 STRUCTURAL MAGNETIC RESONANCE IMAGING OF THE CEREBELLUM IN AUTISM SPECTRUM DISORDER. J. Hamstra*, C.M. Schumann, B.L. Goodlin-Jones, M.H. Buonocore, C.R. Lammers and D.G. Amaral. The M.I.N.D. Institute UC Davis, Sacramento, CA 95817. Both magnetic resonance (MR) imaging and neuropathology studies have implicated the cerebellum in the pathophysiology of autism. Using structural MR imaging, we have examined the cerebellum of male subjects (7-19 years of age) in four diagnostic groups: autism with mental retardation (IQ < 70; n=18), autism without mental retardation (IQ > 70; n=15), Asperger syndrome (n=15), and age-matched typically-developing controls (n=14). Using T1-weighted coronal SPGR images, manual segmentation of the whole cerebellar volume was carried out. The midsaggital area of the vermis and its lobules (anterior lobules I-V, superior posterior lobules VI-VII, and inferior posterior lobules VIII-X) were also measured. We observed no reliable difference for the total cerebellar volume between the four diagnostic groups. Nor did we find any differences in the cross-sectional areas of the vermis either as a whole or when lobules were evaluated. We are currently

carrying out additional segmentation of the cerebellum to investigate potential grey matter or white matter differences and potential differences in lobulues of the whole cerebellum. The lack of cerebellar alterations in this cohort of subjects thus far is in contrast to detected volume changes in the amygdala and hippocampal formation of the same subjects (Schumann et al., This meeting). Study funded by The M.I.N.D. Institute and NIMH. P2.3.9 WHITE AND GRAY MATTER DIFFERENCES IN AUTISM USING VOXEL-BASED MORPHOMETRY. E.D. Bigler, S.L. Provencal, W. McMahon and J.E. Lainhart*. Brain Imaging and Behavior Lab, Brigham Young University, Provo, UT, 84602; Department of Psychiatry, University of Utah, Salt Lake City, UT, 84103. Structural MRI findings using traditional volumetric measurements in autism are often complicated by inconsistent control of variables such as head size and intellectual functioning. This study applied voxel-based morphometry (VBM) to segmented gray and white matter brain volumes of individuals with autism and controls. Data were analyzed using statistical parametric mapping (SPM) techniques. In the first comparison, few significant differences were found between normocephalic, high-functioning autistic subjects (n=28) and normocephalic controls (n=18). Numerous density differences were found, however, in a comparison between autistic individuals with macrocephaly (n=15) as compared to controls with benign macrocephaly (n=9). Gray and white matter differences were prominent in frontal regions, fusiform gyri, superior temporal gyri, and cerebellar hemispheres. Lastly, brain morphometry was examined in a small sample of individuals with low-functioning autism (n=5) verus high-functioning autism (n=28). Gray matter differences were found in the left temporal lobe and bilateral cerebellar hemispheres. Bilateral white matter density differences were noted in superior temporal gyrus. Overall, gray and white density differences were found in regions consistently implicated in the neurobiology of autism. Experimental control of characteristics (e.g., head size and intellectual

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functioning) and the use of these findings in guiding future research are discussed. Funded by NICHD 5 U19 HD035476-07, the NICHD Collaborative Programs of Excellence in Autism, and the Ira B. Fulton Foundation. Poster Session 2: Topic 4: Intervention P2.4.1 IMPROVING EMOTION RECOGNITION USING VIDEO MODELING IN A CHILD WITH AUTISM. M. Abdullah and B.A. Corbett*. UC Davis Department of Psychiatry and Behavioral Sciences and M.I.N.D. Institute, Sacramento CA, 95817. Video modeling is a well-validated behavioral intervention documented in the behavioral sciences. The methodology appears particularly beneficial for children with autism. A case study is presented replicating previous results displaying the efficacy of using video modeling to improve the perception of emotion in a 7-year, 2-month old child with autism and mild mental retardation. The subject was administered cognitive, adaptive and neuoropsychological measures pre- and post-treatment. The video modeling treatment consisted of observing professionally produced videotaped scenes of typically developing children engaged in a variety of play and social scenarios showing four basic emotions: happy, sad, angry and afraid. After each scene, the child was asked to identify the emotion and to engage in a role-play providing the opportunity to model the emotion. The preliminary results, based on neuoropsychological data, demonstrated video modeling to be an effective intervention for the attainment and generalization of emotion perception. Post-testing revealed that the subject showed significant improvement in the perception of emotions via facial expressions and moderate improvement in identifying pantomime actions. The acquisition of skills using video modeling is often very rapid compared to other methods of intervention and requires limited time and personal resources to implement. Further, anecdotal data suggest enhanced play skills and interactions with others.

P2.4.2 VIDEO DOCUMENTATION OF FUNCTIONAL DEVELOPMENT IN A PRESCHOOLER WITH AUTISM IN RESPONSE TO EARLY INTERVENTION USING THE DIR APPROACH (DEVELOPMENTAL, INDIVIDUAL DIFFERENCE, RELATIONSHIP-BASED APPROACH). C.J. Claflin*. Northwest Missouri State University, Maryville, MO 64468. Normative developmental and clinical intervention research supports the usefulness of functional developmental capacities (DC) as a means to document deficits and response to early intervention (EI) (Greenspan, 1992; Tanguay, Robertson, & Derrick, 1998). This longitudinal study documents changes in six DC core to the DIR Approach and ICDL (Interdisciplinary Council on Developmental & Learning Disorders, 2000) Clinical Practice Guidelines over a 15-month intervention in a preschooler with autism. Subject diagnosed with mild-moderate autism, moderate cognitive deficiencies, language development of 5-9 mos at age 37 mos, and exhibited significant deficits in the first DC of shared attention. Intervention video documents progression through the five other DC of engagement; affective reciprocity and gestural communication; complex presymbolic, shared social communication and problem solving; symbolic and creative use of ideas; and the beginnings of logical and abstract use of ideas and thinking. Independent testing scores and educational placement validate progress. Aspects of EI consistent with DIR-approach associated with functional DC are identified. At 41 mos (4 mos of EI), speech/language scores improve to 2-3 year levels. At 46 mos (9 mos of EI), Weschler Verbal IQ: 79, Performance IQ: 95, Full Scale IQ: 85. Currently at 7 yrs 9 mos, child functions independently at grade-level in regular first grade with only remaining diagnosis as mild speech and language delay. Funding sources: Northwest Missouri State University Applied Research Grants #122424 & #122160. P2.4.3 A NURSING INTERVENTION FOR PARENTS AFTER A CHILD IS DIAGNOSED WITH AUTISM SPECTRUM DISORDER: RESULTS OF A PILOT STUDY. E. Giarelli, M. Souders, R. Ittenbach,

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J. Pinto-Martin* and PA-CADDRE. University of Pennsylvania, Philadelphia, PA 19104. Parents of children newly diagnosed with ASD face difficult circumstances and react with disbelief and emotional distress as a result of increased caregiver burden. The primary purpose of this pilot was to refine a parent-focused nursing intervention designed for the post-diagnosis period. A secondary purpose was to test the effect of the intervention by comparing treatment and control groups on published measures of stress and family functioning. Data were collected at baseline and 3 months. A convenience sample (n=29) was randomly assigned to group. The intervention group (n=18) received usual care plus 1 hour of telephone and 2 hours in-home instruction and counseling. Demographics were comparable. Parent age ranged from 33-49 years and the 11 male and 4 female children ages ranged from 2-5 yrs. The most urgent needs of parents were for emotional support from a professional with expert knowledge and guidance to individualize the treatment plan to best meet the child’s behavioral problems and family resources. A larger study is feasible and highly desired by parents. The intervention will be expanded to 4 telephone contacts and 1 home visit over 20 weeks and to include: a family needs assessment, content on problem solving and treatment options, and planned counseling sessions to address multiple psychosocial and informational needs of both parents and siblings. Analysis of group differences on Perceived Stress, Family Inventory of Resources, and Quality of Life Scales were statistically non-significant and attributed to sample size. Analyses of subscales and key items will be completed by January 2004. P2.4.4 PEER-MEDIATED SOCIAL SKILLS TRAINING FOR CHILDREN WITH HIGH-FUNCTIONING AUTISM. K.M. Chung, S. Reavis, M. Mosconi*, J. Drewry, T. Matthews and M. Tasse. Center for Development and Learning, University of North Carolina - Chapel Hill, Department of Psychology, Chapel Hill, NC 27599. A peer-mediated social skills training program combined with video feedback was implemented

with 4 children previously diagnosed with high functioning autism and 4 typically developing peers. Children attended 90-minute weekly training sessions for 12 weeks in order to work on specific social skills. Target skills were identified prior to treatment by parents and included basic conversational skills (e.g. initiating conversation, making contingent remarks, etc.). The children with autism were videotaped during a 5-minute interaction with a typically developing peer and later watched these videotapes with the group while receiving feedback from each child. The effectiveness of the training program was evaluated with parent measures at baseline and post-treatment, as well as a social skill coding system applied to the video-taped dyadic interactions. Two independent raters coded each tape and demonstrated good inter-rater agreement (85%). Parent reports and the coding system each indicate that the individual children with autism showed increases in social initiations and appropriate contingent responses as well as decreases in inappropriate talking. Each target child varied somewhat in their level of improvement as well as in which skills they improved. However, overall results suggest that peer teaching and interactions combined with video feedback are effective strategies for helping children with high-functioning autism learn appropriate conversational skills. P2.4.5 PRACTICE PATTERNS IN COMMUNITY EARLY INTERVENTION PROGRAMS FOR CHILDREN WITH AUTISM: PRELIMINARY FINDINGS FROM THE FIELD. A. Stahmer.* Child and Adolescent Services Research Center, Children’s Hospital, San Diego, CA 92123 Early intervention providers working with children who have autistic spectrum disorders (ASD) must choose from a myriad of treatment options. Although a few specific treatment methods have been established as efficacious for some children with autism in laboratory settings, research examining the translation of these treatments into service systems is virtually nonexistent. Little is known about the types of treatment methods used in early intervention programs, how those methods are chosen and whether the methods used are

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experimentally based. The purpose of the current project was to conduct qualitative research examining the practices of early intervention providers working with children who have a diagnosis of autism under the age of five. Providers in two California counties, San Diego and Riverside, participated in a series of focus groups to help answer the following questions: (1) What methods are providers using in their publicly funded programs; (2) Do providers have an understanding of which treatment practices have a research base? And (3) How do providers adapt research-based practices for use in community settings? There was variability among providers in attitudes about, knowledge and use of experimentally based treatment practices. There was consensus about training and adaptation challenges of using experimentally based treatments. The majority reported they used an eclectic approach, combining treatment based on child needs, individual preference, and external influences such as parent request or program policy. Methods providers use to adapt treatment methods for practice in community environments are discussed. P2.4.6 ECOBEHAVIORAL ASSESSMENT OF INCLUSIVE PRESCHOOL CLASSES INVOLVING CHILDREN WITH AUTISM . S.L. Odom, L. Tsao and K. Hume. School of Education, Indiana University, Bloomington, IN 47405-1006 The purpose of this study was to examine the ecological and behavioral features of inclusive preschool classes in which children with autism participated. Ten preschool-age children with autism or pervasive developmental disorder, ten children with other disabilities matched for cognitive ability and chronological age, and ten typically developing children matched for chronological age were participant. All matched children were enrolled in the same inclusive preschool programs, and the programs were located in California, Maryland, Tennessee, and Washington. Six, 30 minute samples of observational data were collected on each child using the CASPER ecobehavioral assessment. Children with autism tended to more often be located in solitary and 1:1 teaching activities than other children, although a substantial

portion of there time was spend in activities with typically developing children. They were involved less in art and pretend play activities and more in manipulative activities than other children. Children with autism were less socially engaged than other children, and directed more social behavior to adults. Also, they received more adult support than other children. Difference in activity engagement across groups were not found. These finding suggest that intervention to promote social engagement in inclusive preschool program would have been beneficial to children with autism, although they did appear to be receiving support for activity engagement. P2.4.7 THE EFFECTS OF PLAY GROUPS ON SYMBOLIC AND SOCIAL PLAY FOR PRESCHOOL CHILDREN WITH AUTISM IN TAIWAN. T.R. Yang*. The Department of Special Education, National Taipei Teachers College, Taipei, Taiwan. 134 Sec. 2 Ho-Ping E. Rd. Taipei 112, Taiwan Symbolic and Social Play of children with autism are remarkably limited. Any intervention for children with autism should address this issue. The Integrated Play Groups model, which was originally designed by P.J. Wolfberg and A.L. Schuler, was adopted to promote the symbolic and social play of children with autism. To examine whether the symbolic and social play of preschool children with autism were promoted after target subjects participated in the Integrated Play Groups, a withdrawal and reversal single subject research design (A-B-A-B) was adopted. Three play groups were implemented into a preschool classroom located at Taipei City, Taiwan. Each play group recruited one preschool child with autism and two typically developing peers. Every play group was conducted by a special education teacher. Symbolic play was analyzed in terms of no interaction, manipulation, functional, and pretended play. Social Play was analyzed in terms of isolate, orientation, parallel, common focus, and common goal play. The findings showed that three preschool children with autism did increase higher level of symbolic play, functional and pretended play, and

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higher level of social play behaviors, common focus play. Play intervention seems very promising for improving imagination and socialization for preschool children with autism. Key words: Autism, symbolic play, social play, play intervention *This study was funded by Taiwan National Science Council, 91-2413-H-152-015. Poster Session 2: Topic 5: Perception and

Cognition in Early Development

P2.5.1 INFLEXIBLE THINKING OR INFLEXIBLE RESPONDING? ANALYSIS OF ERRORS COMMITTED BY CHILDREN WITH AUTISM ON THE FLEXIBLE ITEM SELECTION TASK . O. Landry, S. Jacques and J.A. Burack*. Dept. of Educ. Psych., McGill Univ., Montreal, QC, Canada H3A 1Y2 The Flexible Item Selection Task (Jacques & Zelazo, 2001) is a measure of cognitive flexibility for use with young children. On this task, children are asked to choose from a set of three images (e.g., a blue boat, a red boat, and a red shoe) two pictures that go together in one way (Selection 1; e.g., blue boat and red boat), and then asked to choose two pictures that go together in another way (Selection 2; e.g., red boat and red shoe). Typically developing children demonstrate difficulty on this task before the age of 5. We tested 14 children with autism (VMA=47.1 mos.; PMA=72.4 mos.) on this task and found that they performed significantly better on Selection 1 than on Selection 2. Performance was then analyzed as a function of trial type (i.e., whether the irrelevant variable was color, size, or shape) and as a function of response type (i.e., correct pair, wrong pair, or same pair). A repeated-measures ANOVA revealed a significant main effect of response type: Participants were less likely to select the same pair across the three trial types than to select the correct or wrong pair (F=5.43, p=0.01). No significant main effect of trial type or interaction was found. The findings that they did not select the same pair twice but that their performance did not

differ from chance suggest difficulties with cognitive (as opposed to response) flexibility. Thus, as is the case with typically developing children, the difficulties displayed on this task by children with autism do not appear to result from response-inhibition problems, but rather, from an inability to switch conceptually between dimensions. (SSHRC Grant Canada). P2.5.2 EXECUTIVE FUNCTIONS IN CHILDREN WITH ASPERGER SYNDROME. V.N. Salimpoor and M.E. Desrocher. Autism Society of Ontario*, York University, Toronto, Ontario, M3J-1P3 Executive functions (EF) are those abilities that allow us to plan and organize future events, as well as initiate, maintain, and shift mental sets. These fontal lobe skills are important for abstract reasoning, judgment, decision making, and problem solving. Previous studies have shown that children with autism experience executive dysfunction; however, results have been mixed with high-functioning individuals and children with Asperger Syndrome (AS). This study investigated the performance of 40 children between the ages of 8-18 with AS on a battery of 15 EF tests, compared with matched control participants. Tests were selected to cover the various domains of EF. Preliminary results show that children with AS experience deficits with problem solving, developing and applying strategies, abstract concept formation, initiation, and shifting of mental set. Furthermore, overall reaction time and speed of processing was slower in children with AS. The clinical and theoretical implications of the findings will be discussed. P2.5.3 COGNITIVE ASSESSMENT OF YOUNG CHILDREN WITH ASD: ATTENTION AND INHIBITORY CONTROL . V. Grindell, C. Bloss and N. Akshoomoff*. Center for Autism Research, Children’s Hospital San Diego, University of California San Diego, San Diego, CA 92037. Autism is a developmental disorder characterized by impaired communication and social skills. Cognitive deficits also accompany these

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impairments in the majority of children with autism. Many factors can interfere with an accurate assessment of a child’s cognitive abilities. This study sought to identify specific, overt behaviors that may contribute to difficulty in accurate assessment of cognitive abilities in young children with autistic spectrum disorders (ASD). A group of 20 children with ASD, ranging in age from 18-48 months, were administered the Mullen Scales of Early Learning. A typically developing group of children matched for age and gender were also administered the test. Videotaped sessions of the test administrations were coded for both off-task and on-task behaviors. Children with ASD spent significantly more time engaged in off-task behaviors, such as whining or crying, and looking away from the task materials in defiance, than the typically developing children. These off-task behaviors interfere with the assessment process and may hamper the child's ability to perform to their full capacity. The relationship between these factors and severity of symptoms will be discussed. ROI NS-19855 P2.5.4 EARLY SOCIAL COMMUNICATION, LANGUAGE, AND THEORY OF MIND IN CHILDREN WITH AUTISM SPECTRUM DISORDER. P. Warreyn and H. Roeyers. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium, B-9000 Introduction-In autism, it has been suggested that a deficit in early social communicative abilities leads to later language problems and a lack of theory of mind. Subjects-20 preschool children with an autism spectrum disorder (ASD) and 20 children without signs of ASD participated in the study. The control group was matched with the ASD group on chronological age and IQ. There was no difference between the groups on language level. Method-The children and their mothers were invited to the University lab. The following components of social communication were assessed: - Imitation of body movements, object manipulations and symbolic play

- Initiating and following of declarative joint attention, social referencing and requesting, during a play interaction with the mother. - Symbolic play abilities, measured by the Test of Pretend Play (Lewis & Boucher, 1997) Theory of mind abilities were assessed by a combination of visual, affective and conceptual perspective taking tasks. All sessions were videotaped and coded afterwards. Results and discussion-Children with ASD especially showed shortcomings on their symbolic play and perspective taking scores. The control group showed more joint attention and imitation than the children with ASD, although these children were not entirely impaired. Social referencing and joint attention were significantly correlated to each other, and showed some correlations with requesting abilities. Imitation abilities were strongly intercorrelated, and formed a correlation cluster with language, pretend play, and perspective taking scores. Slide Session 2: Topic 1: Face Processing I S2.1.1 FACE AND GAZE PROCESSING IN CHILDREN WITH AUTISM . R.M. Joseph, K. Ehrman, C. Connolly and H. Tager-Flusberg. Boston University School of Medicine, Boston, MA, 02118. Experiment 1 investigated holistic face processing in children with autism by comparing their ability to recognize a face part (eyes, mouth) in the context of the whole face in which it was learned with their ability to recognize the same face part in isolation. Following up on Joseph and Tanaka’s (2003) finding that children with autism showed a normal holistic processing bias for the mouth region but generally impaired processing of the eye region, we assessed whether eye recognition would improve if children were visually cued to attend to this region of the face. Children with autism showed only marginal improvement in eye recognition when cued, and no holistic processing effects for eyes whether cued or uncued. In contrast, the comparison group exhibited a holistic processing bias for eyes in the uncued condition as well as in the cued condition, in which their performance improved

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significantly. Experiment 2 examined the same children’s tendency to orient reflexively to peripheral targets in response to central, non-predictive gaze and arrow cues. Whereas comparison participants oriented reflexively to gaze and arrow cues, children with autism oriented reflexively to arrows, but showed an attenuated orienting response to gaze. S2.1.2 CAN PEOPLE WITH AUTISM FIND A FACE IN THE CROWD? C. Ashwin, S. Wheelwright and S. Baron-Cohen*. Autism Research Centre, Depts. of Experimental Psychology and Psychiatry, University of Cambridge, Cambridge UK CB2 2AH. Previous research on face-processing suggests that people with autism use a more feature-based strategy and have difficulty identifying facial expressions of emotion. However, findings have been inconsistent and results from recent research have raised questions. To investigate this area further we used a visual search paradigm with neutral, threatening and friendly schematic faces. The threatening and friendly faces had exactly the same features, but in reversed orientation to each other in order to produce the appropriate emotion. Previous research has shown that threatening faces are found quicker and more accurately than friendly faces, which is known as the “anger superiority” effect. Our aims were to investigate whether controls and people with autism showed the anger superiority effect. To show this effect, a participant would have to: (1) process faces holistically, and (2) recognise the emotional expressions. We compared reaction times and accuracy to finding a threatening face versus a friendly face, while varying crowd size, crowd type, display time, and orientation. Results showed, surprisingly, that both the control and autism groups identified threatening faces faster and more accurately than they identified friendly faces. This effect disappeared for the autism group when faces were inverted, but remained intact for the control group. These findings suggest that people with autism can judge threatening vs. friendly intent from facial expressions, but might be using a different strategy since this is effect is easily disrupted by inversion.

This research was funded by a grant from the MRC UK. S2.1.3 STRAIGHT GAZE ACCELERATES DETECTION, BUT DIRECT GAZE DOES NOT: THE CASE OF AUTISM . A. Senju, Y. Kunihira, T. Hasegawa and Y. Tojo. Dept. of Cognitive and Behavioral Science, Univ. of Tokyo, Tokyo, 153-8902, Japan. Atypical pattern of mutual gaze behavior is one of the crucial characteristics in individuals with autism. Current study adopted visual search paradigm to investigate whether perceived mutual gaze facilitate detection latency in children with and without autism. In Experiment 1, targets and distracters were either eyes with center-, leftward- or rightward-looking gaze, as in von Gr¤au and Anston (1995). Results revealed that children with autism, as well as typically developing children, were faster to detect eyes with center (or straight) gaze among leftward- and rightward-gazing eyes than vice versa. In Experiment 2, participants detected target faces with either direct gaze or averted gaze. Laterally averted faces were used to eliminate lower perceptual characteristics such as symmetry, which were inherent with the ” straight gaze• used in Experiment 1. As in Experiment 1, typically developing children were faster to detect direct gaze than averted gaze. However, gaze direction made no effect on the detection speed of children with autism, which contrasts with the results in Experiment 1. These results suggest that children with autism can detect and orient to others• ” straight gaze• when lower perceptual property such as symmetrical feature are available, but fail to preferentially detect “direct gaze” which can only be perceived with the reference of facial orientation. Implications for the atypical mutual gaze behavior will be discussed. S2.1.4 PHENOTYPIC SUBTYPING OF INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS BASED ON PHYSIOLOGICAL INDICES OF AROUSAL PILOT DATA REPORT . S.S. Cohen, H.B. Perry, R.J. Hagerman* and D.

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Hessl*. M.I.N.D. Institute, University of California, Davis Medical Center, Sacramento, CA, 95817 Autism is widely recognized as a heterogenous disorder with multiple etiologies. In an effort to subtype autism, we have utilized physiological measures of the autonomic nervous system to examine individual differences in response to various emotional and social probes. Sympathetic tone is assessed using electrodermal response, a measure of eccrine sweat gland activity. Parasympathetic arousal is indexed via changes in vagal tone. The potentiated startle reflex is a well-validated physiological measure mediated by amygdala function and associated with anxiety and fear in human and animal studies. Fragile X syndrome, a single gene disorder, is one of the most common known causes of autism. In our studies, we have contrasted physiological and behavioral profiles of children with idiopathic autism, with those children who have co-morbid diagnoses of fragile X syndrome and autism. This comparison between known and unknown causes of autism can serve as potential model for subtyping this complex disorder. Children, 6-18 years-old, view a series of emotionally evocative stimuli (human faces and non-human objects), and also engage in an interaction with an unfamiliar investigator while the physiological measures are collected. We will present a preliminary comparison of the physiological data with behavioral measures of stress, fear, and anxiety in children with autism, with and without co-morbid fragile X syndrome. Funding for this project provided by the M.I.N.D. Institute, and by the Department of Psychiatry, University of California, Davis Medical Center S2.1.5 ACTIVATION OF THE FUSIFORM GYRUS WHEN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER VIEW FACES. N. Hadjikhani, R.M. Joseph, C. Chabris, J. Clark, S. Steele, L. McGrath, M. Vangel, J. Snyder, I. Aharon, E. Feczko, G.J. Harris and H. Tager-Flusberg*. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. Prior imaging studies have failed to show activation of the fusiform gyrus in response to non-

emotional faces in individuals with autism spectrum disorder (ASD)(Schultz et al., 2000, Pierce et al., 2001). However, individuals with ASD do not typically exhibit dramatic behavioral deficits that might result from fusiform gyrus damage such as in prosopagnosia, and their deficits extend well beyond face perception to include social cognition (Mundy, 2003). In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high field (3 Tesla) functional magnetic resonance imaging to study face perception in 11 individuals with autism spectrum disorder (ASD) and in 10 normal controls. We used face stimuli, object stimuli and sensory controls (Fourier scrambled versions of the stimuli) containing a fixation point in their center to ensure that our participants were looking at and attending to the stimuli. Our data show that individuals with ASD activate the fusiform face area and other brain areas involved in face processing when viewing faces as compared to non-faces. These data indicate the face processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the network of brain areas involved in face processing. S2.1.6 FUNCTIONAL AND STRUCTURAL SUBSTRATES OF AFFECTIVE PROCESSING IN AUTISM: REFRAMING THE ORIGINS OF FUSIFORM HYPOACTIVATION . R.J. Davidson*, K.M. Dalton, B.M. Nacewicz, A.L. Alexander, M.A. Gernsbacher and H.H. Goldsmith. W.M. Keck Laboratory for Functional Brain Imaging and Behavior, Waisman Center, University of Wisconsin-Madison, 53705 This talk will summarize 3 studies examining functional and structural bases of affective processing in autism. In study I, subjects with autism and controls were presented with emotional and non-emotional faces, directed at the viewer or not, during a task that required discrimination between emotional and neutral faces while undergoing fMRI. Eye tracking was used in the scanner. Subjects with autism showed less activation in the right fusiform compared with controls. However, this was driven by gaze fixation. Duration of fixation on the eye region

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was highly predictive of fusiform activation. In response to emotional faces, subjects with autism showed highly significantly elevated activation in amygdala, orbital frontal cortex and anterior cingulate. In study II, the fusiform activation difference between subjects with autism and controls was replicated using highly familiar faces. Again, gaze fixation strongly predicted fusiform activation. A third study examined volumetric differences in amygdalae between groups. There were no significant differences in amygdala volume, but subjects with autism exhibited significantly greater variability compared with controls. Those subjects with autism who had the smallest amygdalae volumes showed the most aberrant behavior and functional activation. The implications of these findings for the role of elevated anxiety in response to social stimuli playing a causal role in gaze aversion and abnormal face processing, resulting in decreased fusiform activation will be discussed. Slide Session 2: Topic 2: Language Processing S2.2.1 FACIAL SPEECH PROCESSING IN CHILDREN WITH AUTISM . K. Condouris, R.M. Joseph, K. Ehrman, C. Connolly and H. Tager-Flusberg. Lab of Developmental Cognitive Neuroscience, Boston University School Of Medicine, Boston, MA, 02118-2526. The bimodal integration of auditory and visual information from the face, known as facial speech, is well-documented. When auditory and facial speech information are congruent, facial speech can serve to disambiguate heard speech; when auditory and facial speech are incongruent, “illusory” percepts result. Given autistic children’s atypicalities in face processing, deficits in crossmodal integration, and impairments in language, their ability to integrate facial speech information with auditory speech is of great interest. The current study investigated bimodal speech perception in 24 children with autism and an IQ- and language-matched comparison group. Using a McGurk-type paradigm, auditory synthesized syllables and visual exemplars for the three syllables /ba/, /da/, and /va/ were

presented on a computer screen in auditory-alone and auditory-visual conditions. In the auditory-visual condition, congruent syllables were presented to assess facial speech influence under naturalistic conditions, and incongruent syllables were presented to assess variations in facial speech influence. In the auditory-visual congruent condition, both groups showed improved speech perception accuracy relative to auditory alone. In the incongruent condition, children with autism as a group showed reduced influence of facial speech. However, a small number of children with autism performed like the comparison group, showing strong facial speech influence. Individual differences in the influence of facial speech were not related to level of language functioning. S2.2.2 LIMITED EFFECTS OF LABELING ON COGNITIVE FLEXIBILITY IN CHILDREN WITH AUTISM. S. Jacques, N. Russo, T. Flanagan, O. Landry, D. Berringer and J.A. Burack. Dept. of Educ. Psych., McGill Univ., Montreal, QC, Canada H3A 1Y2 People with autism display poor language abilities relative to their nonverbal abilities and exhibit difficulties on tasks that require cognitive flexibility, the ability to take conflicting perspectives on a single object or event. We recently suggested that difficulties with cognitive flexibility in people with autism might be causally linked to their language difficulties and found that the performance of children with autism on the Flexible Item Selection Task (FIST) correlated with their language abilities (Jacques et al., 2002). However, we did not manipulate language experimentally. Thus, to assess whether children with autism benefit from experimental language manipulations, we administered two counterbalanced versions of the FIST to 40 children with autism-spectrum disorders (CA= 9.8 yrs.; rec. VMA= 7.1 yrs.; exp. VMA= 6.6 yrs.; NVMA= 7.5 yrs.) including a labeled version in which the experimenter labeled relevant information and an unlabeled version. As predicted, children’s performance on FIST correlated with their receptive and expressive VMAs. Also, children who spontaneously labeled relevant information themselves during the task (n=24) scored higher

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than those who did not, even when receptive or expressive VMA were covaried. However, unlike typically developing preschoolers who benefit from both their own as well as an experimenter�s labels, children with autism did not benefit from the experimenter’s labels. The finding that children with autism only benefit from labels they generate themselves is relevant for theoretical accounts of autism and for language-based interventions designed to improve cognitive functioning in this population. S2.2.3 LANGUAGE PROFILES IN HIGH-FUNCTIONING CHILDREN WITH ASD . T. Loucas, S. Chandler, G. Baird, T. Charman, E. Simonoff and A. Pickles. School of Medicine & Biomedical Sciences, King's College London, London SE1 3SS, United Kingdom. Language functioning in a population-representative sample of high-functioning 11-year old children with autism spectrum disorder (ASD) was investigated using a range of psychometric measures. The children’s diagnoses were confirmed by ADI-R, ADOS and clinical evaluation; cognitive performance was assessed using the WISC-III (UK), BPVS-2 and CELF-3 (UK). The data for 19 children meeting criteria for autism and 45 children with a pervasive developmental disorder (PDD) with Full Scale IQs of 70 or above were analysed. Taking both groups together, FSIQ and receptive vocabulary were well within the average range (FSIQ = 90.3, SD=15.1; BPVS = 95.8, SD=14.6). Performance on the CELF-3 was weakest (Total Language = 80.4, SD=13.5) and was significantly lower than Verbal IQ (mean=92.2, SD=15.7). This pattern of performance was the same for autistic and PDD groups taken individually. A comparison of the CELF-3 Receptive and Expressive subscales showed that, when IQ-level was controlled for, receptive language was weaker than expressive language for the PDD but not the autistic children. For the autistic children there was a non-significant trend towards weaker expressive language. Whilst language ability and IQ are highly correlated, language is relatively impaired in ASD when IQ is controlled for. In autistic children, both receptive and expressive language are equally impaired, whereas

for children on the broader autism spectrum expressive ability is spared relative to receptive language. (Submitted 12/12/03, resubmission to add: This research was funded by an independent research-funding charity, the Wellcome Trust) S2.2.4 INTONATION AND CONTENT IN SARCASM UNDERSTANDING BY PARTICIPANTS WITH AUTISM, WITH AND WITHOUT LANGUAGE IMPAIRMENT . S. Pearlman-Avnion*; K. Condouris; L. Evancie, K. Ehrman and H. Tager-Flusberg. Lab of Developmental Cognitive Neuroscience, Boston Univ. Sch. Of Med., Boston, MA, 02118-2526. The contribution of intonation and content to the comprehension of sarcasm (Ackerman, 1981; 1983) was examined in 21 participants with autism, with and without language impairment (ALI and ALN respectively). Twelve stories with a sarcastic and a literal version were digitally audio taped, ending with exactly the same utterance, offering sarcastic or sincere interpretation depending on the story version. Each participant listened to 6 sarcastic and 6 literal stories, half of which were accompanied by a congruent intonation (sincere utterance after a literal story, or a sarcastic utterance after a sarcastic story), and half by incongruent intonation (sincere utterance after a sarcastic story or a sarcastic utterance after a literal story). Following, participants were asked if the person in the story meant what he said in the utterance, and accordingly how did they know if he meant it or not. Finally participants were asked to judge if that person was happy or sad. In contrast to previous findings indicating a tendency towards literal interpretation of sarcasm in participants with autism, the present results revealed such a deficiency only for the ALIs, with a near-to-ceiling performance for the ALNs. In addition, ALNs were tuned to a sarcastic intonation when it accompanied a literal story, similarly to typically developing participants, yet ALIs were susceptible to the intonation in both incongruent combinations, revealing a tendency to make rapid judgments about other people’s mental states based on their vocal expressions, ignoring what the content might have suggested.

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S2.2.5 EARLY LANGUAGE COMPREHENSION VIA PREFERENTIAL LOOKING . L. Swensen, E. Kelley, J. Latz, D. Fein and L. Naigles. Univ. of Conn., Storrs, CT 06269. It is unknown to what extent autistic children show normal language acquisition processes. By 15 months, typical children understand an ambiguous word (“toopen”) to refer to a novel object rather than its action (Noun Bias). By 17 months they differentiate identical words in different orders. Preferential looking has proved useful in demonstrating comprehension in normal infants. The present study used preferential looking to study autistic children’s responses to noun bias and word order paradigms. Participants were 11 children with autism (mean age=35 months). Side-by-side videos were presented with a linguistic stimulus that matched one of the videos. Eye movements were coded for percent time looking to the video matching the linguistic input. To test Noun Bias, six novel active puppets were labeled with nonsense words. Test trials compared the (old) puppet doing a new action with a new puppet doing the old action. Word Order was tested with six verbs (“the girl washes the boy” vs. “the boy washes the girl”). The autistic children looked longer (p<.05) at the familiar animal than the action, demonstrating noun bias on all six trials. They also looked longer (p<.05) at the matching screen for five of the six word order trials. These autistic children, therefore, whose mean MLU (1.4) was at about a 20 month language level, displayed the noun bias and word order sensitivity found in 1-to-2-year-old typical children. Like typical children, they comprehend word order before they produce it. Finally, preferential looking appears useful for demonstrating competence in children with autism. Funded by the National Alliance for Autism Research Slide Session 2: Topic 3: Genetics II S2.3.1 DETECTION OF ALLELIC INTERACTION IN ASSOCIATION TO AUTISM: APPLICATION TO THE 15q12 GABAA RECEPTOR SUBUNIT

REGION. J.L. McCauley, L.W. Hahn, E.R. Martin, J.H. Moore and J.S. Sutcliffe*. Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232 and Center for Human Genetics, Duke University, Durham, NC 27710. Chromosome 15q11.2-q13 is a candidate region for autism susceptibility based on chromosomal duplications and findings of linkage and association in autism. Evidence points to a cluster of GABAA receptor subunit genes (GABRB3, GABRA5, GABRG3) as being prime candidates based on increased linkage in phenotypic subsets of autism and association. Given that GABAA receptor subunits associate to form a heteropentameric receptor complex, we hypothesized that disease risk associated with this complex could involve interaction between alleles within 15q12 or also involving other GABAA subunit genes. To test this hypothesis, we analyzed genotype data from 158 families for 59 SNP markers across the 1-Mb gene cluster applying a novel method that allows detection of allelic interaction using family data structures. The MDR-PDT combines the Multifactor Dimensionality Reduction (MDR), designed to permit detection of gene-gene interaction using case-control data, and the Pedigree Disequilibrium Test (PDT), designed to carry out valid single-locus tests of linkage disequilibrium in general pedigrees. MDR-PDT uses cross-validation and permutation testing to estimate prediction errors, calculate significance and control for type I error due to multiple comparisons in identifying the combination of alleles that are positively correlated with disease. This analysis revealed a significant (P<0.01) three-way interaction involving alleles in GABRB3 and GABRA5. These data further support involvement of GABRB3 and GABRA5 in autism susceptibility. S2.3.2 INVESTIGATION OF GENE-GENE INTERACTIONS IN AUTISTIC DISORDER. A.E. Ashley-Koch, H. Mei, J. Jaworski, E.R. Martin, M.M. Menold, M. Cuccaro, J.R. Gilbert and M.A. Pericak-Vance *. Duke University Medical Center, Durham, NC, 27710. Autistic disorder (AD) has a complex genetic architecture with evidence for susceptibility loci on

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several chromosomes. We hypothesize that some of these genes may act epistatically to contribute to AD susceptibility. Thus, we have examined 210 multiplex (including 99 from AGRE) and 175 singleton AD families for gene-gene interactions among AD candidate genes on chromosomes 2, 7, 15, 17 and 19. We have used a novel statistical method, the multilocus genotype-PDT, to detect multi-locus associations, as well as the pattern recognition approach of the multifactor dimensionality reduction (MDR) method to detect such epistatic interactions. Examination of the multiplex families alone indicate that the most significant two-locus associations detected with the genotype-PDT occur between a SNP in the SLC6A4 gene on chromosome 17 (RS140700) and two SNPs in the RELN gene on chromosome 7 (RELN_59 and REEXN45AG; uncorrected p-values were 0.0007 and 0.0006, respectively). Examination of the combined multiplex and singleton data set by the MDR method detected potential interactions among the GABAA receptor subunit genes on chromosome 15 (GABRb3, GABAa5 and GABAg3), as well as APOE on chromosome 19 with RELN. Further analysis will be required to determine if the interactive effects detected by these multi-locus analyses are simply a reflection of the main effects of the markers, or truly detecting interactive effects. S2.3.3 A GENOMIC SCREEN AND EVIDENCE FOR GENE-GENE INTERACTION IN AUTISM. J.S. Sutcliffe*, L.M. Olson, S.E. Folstein, J.L. Haines and J.L. McCauley. Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232. Idiopathic autism exhibits a complex genetic etiology and may involve inheritance of alleles at as many as fifteen or more genes. Several genomic screens in multiplex autism families have identified numerous loci across the genome, and a few of these (e.g. 7q, 2q) have been replicated across multiple studies. A limitation of studies to date is a restriction of analyses to algorithms that detect only main effects, in which allele(s) at a given locus act independently of other loci in the genome. Gene-gene interaction, or epistasis, would hinder attempts to identify loci using standard analytical paradigms

(i.e. linkage and association) and could explain failure to replicate linkage. We recently completed a genomic screen in 144 multiplex autism families and identified six chromosomal regions exhibiting multipoint heterogeneity LOD (HLOD) scores >1.5. Promising results included findings of linkage on 17q at 50 and 70 cM (HLODs = 2.64 and 1.86) and a peak on 19p (HLOD = 2.42). Chromosomes 3p, 6q, 12p and 16p were also detected (HLOD > 1.5). To test the hypothesis that gene-gene interaction effects exist in autism, we have performed exploratory studies in which linkage at a suggestive locus is used as a covariate in analysis of linkage elsewhere in the genome. This approach has revealed a significant (P<0.05) interaction between the 19p locus and the more distal region on 17q. Significant interactive effects were also observed for other locus combinations. These data support involvement of 17q and 19p and highlight the need to consider the potential of epistatic effects in genetic analysis of autism. S2.3.4 EVIDENCE SUPPORTING THE MULTIFACTORIAL THRESHOLD MODEL IN AUTISM. C. Wolpert 1, J. Grubber 1, S. Donnelly 1, H. Wright 2, J.R. Gilbert 1, M. Cuccaro 1, M.A. Pericak-Vance 1. 1 Center for Human Genetics, DUMC, Durham, NC 27710. 2 USC, Columbia, SC 29202 The MTM predicts a higher genetic load is necessary to cause discrete traits in the less frequently affected sex. Since the male:female ratio in autism is 4:1, we hypothesized autistic females have a higher genetic load than autistic males as manifested by increased clinical severity (e.g. earlier age of onset (AOO), greater developmental impairment). We analyzed these variables in 139 Fhx- families (one individual with autism, no family history of autism) and 95 Fhx+ families (+ family history of autism). All individuals met ADI-R criteria. The Vineland Adaptive Behavior Scales (VABS) was used to assess adaptive functioning. In the overall data set, females (N=56) showed lower VABS communication (p=0.03) and adaptive behavior composite scores (ABC; p=0.03) than males (N=178) but equivalent AOO. When stratified by family history status, Fhx- females (N=28) had

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significantly lower VABS scores than Fhx- males (N=111) on communication (p=0.002), daily living skills (p=0.013) and ABC (p= 0.009) scores. Fhx- females also showed significantly earlier AOO than Fhx- males (ADIq5, p =0.03; ADIq94, p=0.05). No gender differences were noted in Fhx+ families for adaptive behavior or AOO. In summary, Fhx- females show earlier AOO and more impaired adaptive behaviors than Fhx- males. These indices may have etiologic relevance in sporadic cases of autism. For example, different genes may segregate in Fhx- families than in Fhx+ families. Furthermore, AOO, sex, and family history data have potential for use in statistical modeling to further refine the search for genetic factors associated with autism. Slide Session 2: Topic 4: Early intervention S2.4.1 INTERVENTION FOR INFANTS WITH AUTISTIC FEATURES: IMPLEMENTATION ISSUES. J. Brian 1*, S. Bryson 2, W. Roberts 1, P. Szatmari 3 and L. Zwaigenbaum 3. 1 Hospital for Sick Children/University of Toronto, ON, M5G 1X8; 2 Dalhousie/IWK, NS; 3 Hamilton Health Sciences/McMaster, ON, Canada. As a result of focused efforts to identify children with signs of autism as early as possible, some children are coming to attention at 2 years of age or younger. Existing literature identifies the importance of fostering social-communication and play development with this age group, although outstanding questions remain. In the course of our ongoing prospective study of high-risk infants (siblings of children with autism), we have identified early signs in several children at 12-24 months (many of whom have subsequently been diagnosed with autism). This has led us to develop an individualized, target-based program that incorporates developmental and behavioral principles into the context of naturalistic infant-caregiver social-communication and play interactions. We summarize our initial experience with this unique group to highlight the potential benefits of intervening at this early age, as well as some of the implementation challenges and how

they can be addressed. Challenges include reduced social engagement and motivation, extreme reactivity, limited communicative intent and reduced awareness of social contingencies. Some strategies to address these challenges include using exaggerated affect, creating highly motivating activities, capitalizing on intense interests, operating within an optimal level of arousal, and explicitly targeting contingency learning. We hope to generate discussion about intervention targets, implementation considerations, and future directions in the ongoing refinement of intervention programs for infants. Funding source: Grant S2.4.2 TEACHING THE IMITATION AND SPONTANEOUS USE OF GESTURES IN YOUNG CHILDREN WITH AUTISM . B. Ingersoll* and L. Schreibman. Autism Research Program, Univ. of Calif., San Diego, CA 92093. Young children with autism exhibit deficits in imitation skills. These deficits are particularly pronounced in the imitation of gestures. Traditional imitation training procedures are typically adult-directed, implemented in a highly structured environment, and target non-meaningful gestures, which inhibit generalization. Reciprocal imitation training (RIT) is a child-directed imitation intervention designed to increase object imitation in children with autism in an interactive play context. This study used a multiple-baseline design across three participants to assess whether RIT could be adapted to teach the imitation of meaningful gestures and whether this would lead to an increase in the participants’ spontaneous use of gestures. Results indicate that gesture imitation can be taught effectively in an unstructured, play environment and that this procedure leads to an increase in the spontaneous use of descriptive, affective, and conventional gestures in young children with autism. Research supported by the M.I.N.D. Institute Scholars Program.

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S2.4.3 THE EFFECTS OF JOINT ATTENTION TRAINING ON LANGUAGE, PLAY, AND SOCIAL SKILLS IN YOUNG CHILDREN WITH AUTISM. C. Whalen. * University of Washington Autism Center, Seattle, WA 98195 and Schreibman, L. Autism Research Laboratory, University of California, San Diego 92093 Young children with autism often demonstrate deficits in joint attention. Joint attention is believed to be related to the development of other skills including language, play, and social skills. Because of this relationship, joint attention is often described as a pivotal behavior and many researchers believe that joint attention training may positively impact the development of other skills in young children with autism. In this study, four children with autism (ages 3-4 years) participated in a joint attention intervention and a multiple-baseline design across participants was used to assess the collateral effects of the joint attention training on language, play, imitation, positive affect, and social initiations. Results indicate that joint attention may help to facilitate the development of these skills, that these skills are likely to be maintained, and that these improvements are likely to generalize to interactions with parents. S2.4.4 PERCEIVED RELATIONSHIPS WITH SERVICE PROVIDERS AMONG PARENTS OF CHILDREN WITH AUTISM. N.O. Davis, A.S. Carter* and J.C. Kuhn. Psych. Dept. UMass. Boston, Boston, MA 02125. Understanding perceived relationships with service providers among parents of children with autism is essential for improving child and family interventions. Psychotherapy outcome research indicates that positive client-provider relationships or 'working alliances' contribute to positive outcomes. In this study, Horvath and Greenberg's Working Alliance Inventory (1989) was adapted to assess parents' perceptions of their relationship with their child's service provider. Participants were 19 parents who responded to an internet survey. Children had a mean age of 9.1 and 75% were boys. Reliability analysis indicates strong internal consistency (alpha=.90). Relationships between working alliance

and child and parent functioning were explored. Results indicate that parents of children with more problem behaviors and parents who were worried about children's behavior reported a weaker connection and less confidence in their child's care provider (rs=-.55 to -.74). Worry about child language was not related to relationship ratings. Although general parenting stress was not related to working alliance in this small sample, stress specific to children's difficult behaviors was correlated with ratings of working alliance (r=-.45). Despite reports of high symptom levels, depressive symptoms were not correlated with working alliance. These preliminary results suggest that parents are less positive about and have less confidence in intervention providers when children have challenging behaviors. Parents may feel that help from providers is less consistent with the challenges they face. Future studies should explore how working alliance may impact interventions for children and families. *Supported by NAAR and NIMH S2.4.5 AUTISM AND STRONGER FAMILIES: AN EARLY INTERVENTION PERSPECTIVE. D. Keen, M. Braithwaite, S. Rodger and A. Jobling. University of Queensland, Brisbane, Queensland 4072, Australia In order to access most forms of early intervention in Queensland, Australia, a definitive diagnosis of autism is required. However, even with this diagnosis services often have extensive waiting lists and provide either workshop-format support for parents or centre-based intervention for the child. Families facing these difficulties identified a need for a family-focused, strengths-based approach, accessible on the basis of a diagnosis of autism or early signs of the disorder. Researchers/clinicians from the University of Queensland collaborated with families and with members of autism support groups to develop the Stronger Families and ASD Project. Families participate in parent workshops, home facilitation sessions and community meetings. These activities provide opportunities for building greater connectedness within families, social networks and local communities. Home facilitation involves

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supporting families to identify priorities and goals for both the family and the child with autism. The home facilitator then supports the family to implement techniques to meet these goals by working with the child,s existing strengths and interests. An action research approach, consistent with the family-centred philosophy of the project, is used to ensure ongoing input from families. This presentation will outline the Stronger Families and ASD Project, and report on parent and child outcomes. The presentation will be of particular relevance to delegates interested in a family-centred, strengths-based approach to early intervention. Funded by Commonwealth Department of Family and Community Services. S2.4.6. PREDICTORS OF MATERNAL SELF-EFFICACY: PARENTING STRESS, GUILT, AGENCY, & AUTISM KNOWLEDGE. J.C. Kuhn*, A.S. Carter* and M. Belzince. Psych. Dept. UMass. Boston, Boston, MA 02125 Given the challenges of raising a child with autism, learning more about multiple dimensions of parenting experience may inform interventions for these families. Self-efficacy, defined as a parents¡¯ sense of competence in their parenting role has been linked to parenting stress and depression. Using new measures, associations between self-efficacy and 1) agency for promoting child development; 2) guilt in the parenting role; and 3) autism knowledge were investigated. Participants were 66 mothers of a child with autism spectrum disorders who completed an internet survey. Mothers¡¯ mean age was 36.5 years (range=20-49) and children¡¯ s mean age was 4.7 years (range=2.4¨C6.9). New continuous measures showed good internal reliability (¦Ás>.79). We predicted that controlling for demographic characteristics, low self-efficacy would be associated with autism diagnosis (versus Aspergers or PDD), and depression, high parenting stress, high guilt, low agency, and low autism knowledge. Counter to expectations, demographic characteristics, autism diagnosis, and maternal depression were not associated with self-efficacy. Consistent with hypotheses, agency, guilt, parenting stress and

autism knowledge were significantly correlated with self-efficacy. However, autism knowledge was negatively associated. This may reflect higher expectations among educated mothers with internet access. When entered into a multiple hierarchical regression equation, only guilt did not contribute unique variance in the model (F(4,61)=15.3, p<.001, Adj. R2 =.47). Efforts to promote parental self-efficacy may be informed by considering the role of these previously unexplored aspects of parental experience. *Supported by NAAR Slide Session 2 Topic 5: Early indicators in

Sutism Spectrum Disorder

S2.5.1 VISUAL FIXATION DURING VIEWING OF NATURALISTIC SOCIAL SITUATIONS IN 2- TO 3-YEAR-OLD CHILDREN WITH AUTISM SPECTRUM DISORDERS. A.Klin*, W. Jones, K. Chawarska and F.R. Volkmar . Yale Child Study Center, New Haven, CT 06520. One of the hallmarks of early symptomatology in children with autism is reduced visual social engagement. We used eye-tracking technology to trace and measure visual fixation patterns of 2- to 3-year-old children with autism spectrum disorders (ASD) while they were viewing a range of naturalistic, videotaped social scenes. These included a single adult's social approach and toddlers at play. Measures of visual fixation obtained for the young children with ASD relative to developmentally-matched controls indicate abnormalities that mirror the results obtained for older individuals with autism previously reported by us. These include markedly reduced fixations on eyes and significantly increased fixations on mouth and body areas as well as greatly increased fixations on inanimate objects. Individual children's visual scanning tracings illustrate in greater detail the abnormal patterns of preferential visual attention displayed by children with ASD relative to controls. Implications of these results for theories of the pathogenesis of autism and for current efforts to

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identify vulnerabilities for autism at the earliest possible age are discussed. Funding agency: National Institute of Mental Health (STAART grant U54-MH066494), and National Institute of Child Health and Human Development (R01-HD042127-02). S2.5.2 RED FLAGS OF AUTISM SPECTRUM DISORDERS IN THE SECOND YEAR OF LIFE . A. Wetherby and J. Woods. FIRST WORDS Project, Florida State University, Tallahassee, FL 32306-7814. The purpose of this prospective, longitudinal study of the FIRST WORDS Project is to identify more precise early indicators of autism spectrum disorders (ASD) by examining videotaped communication samples collected during the second years of life for three groups of children: one with ASD, one with developmental delays in which ASD was ruled out (DD), and one with typical development (TD) matched on age and gender. The children were identified from a pool of 3,026 children from the general population who were screened with the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP, Wetherby & Prizant, 2002) Infant-Toddler Checklist between 12 and 24 months of age. The CSBS DP Behavior Sample was videotaped on selected children during the second year of life and these videotapes were reanalyzed to identify red flags of ASD. The results indicated that nine red flags differentiated children in the ASD group from both the DD and TD groups and four red flags differentiated children in the ASD Group from the TD group but not the DD group. The 13 red flags were found to discriminate the three groups with a correct classification rate of 94.4%. These results have important implications for earlier identification of ASD, which will enable earlier intervention. This work was supported by two grants from the U.S. Department of Education, Office of Special Education and Rehabilitation Services (H324M980173 and H324C030112) and a grant from the U.S. Department of Education, Institute of Education Sciences (R305T010262).

S2.5.3 REPETITIVE BEHAVIORS IN AUTISM ACROSS DEVELOPMENT M. Cuccaro, S.L. Donnelly, R.K. Abramson, C.M. Wolpert, S.A. Ravan, H. Cope, H.H. Wright, A. Hall, R.L. Gabriels and M.A. Pericak-Vance*. Duke University, Durham, NC 27710. Restricted and repetitive behaviors and interests (RBs) are a defining feature of autism. Changes in RBs were examined across development (chronological age and developmental level) using a cross sectional design. 162 participants with autism between the ages of 3 and 21 years were drawn from a larger group of individuals involved in an autism genetics study. Participants consisted of 130 males (mean age = 94 months, sd = 45) and 32 females (mean age = 105 months, sd = 44) from trio (single individual with autism) and multiplex (more than one individual with autism) families. A standard protocol of clinical diagnostic and behavioral assessments including the Autism Diagnostic Interview-Revised (ADI-R), Aberrant Behavior Checklist (ABC), and Vineland Adaptive Behavior Scales (VABS) was completed for all participants. Analyses indicated that neither the ADI-R Repetitive Domain nor ABC Stereotypy factor score was correlated with adaptive developmental level. Age was significantly negatively correlated with the ADI-R Repetitive Behavior domain score (Pearson r = -0.20, p = 0.006, n = 162) but not the ABC Stereotypy score (Pearson r = -0.51, p = 0.26, n = 162). Group comparisons (based on age) revealed that younger children showed significantly more RBs based on the ADI-R Repetitive Domain score (p = 0.037). The results suggest that select RBs may change with age and merit further study. S2.5.4 REGRESSIVE AND NON-REGRESSIVE AUTISM: EFFECTS ON EARLY DEVELOPMENT . S.J. Rogers and S. Hepburn. Funded by *NICHD U19HD35468* one of the CPEA Network projects. carried out at Univ. Colo. Health Sciences Ctr, Denver, CO, 80262. Objectives: to explore developmental correlates of regressive onset of autism in very young children with autism.

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Methods: we enrolled 25 two year olds carefully diagnosed with autism. The children had no medical conditions associated with their autism. All walked by 15 months and categorized their onset course and regressive or not based on ADI regression questions and a regression questionnaire by C. Lord. Assessment measures included Mullens, Merrill-Palmer, ESCS, and ADOS. Results: 11/25 children reported regression with complete loss of speech at a mean age of 17 months. No medical cause for the regression was found for any of the children. The regressive subgroup was significantly more impaired than nonregressive on visual-spatial tasks of Merrill Palmer and on sharing affect in ESCS, but not on joint attention, IQ, play, or language development. There was also a 10-point IQ difference that approached significance. Conclusions: onset of autism via regression and speech loss in toddlerhood is related to greater impairments in both cognitive and affective domains than gradual onset. This is the youngest group of subjects studied concerning the developmental profile of regression, and results support earlier reports of more severe deficits in some areas in children with regressive history. S2.5.5 CHANGES IN RED FLAGS OF AUTISM SPECTRUM DISORDERS FROM THE SECOND TO THE THIRD YEAR OF LIFE. S. Shumway, A. Wetherby, J. Woods and N. Watt. FIRST WORDS Project, Florida State University, Tallahassee, FL 32306-7814. The purpose of this prospective, longitudinal study of the FIRST WORDS Project is to determine whether red flags of autism spectrum disorders (ASD) identified in the second year of life change in the third year of life in children later diagnosed with ASD. The CSBS DP Behavior Sample was videotaped during the second year of life and again during the third year of life for fifteen children who were later diagnosed with ASD and these videotapes were analyzed to identify red flags of ASD. The video analysis indicated that 13 red flags of typical and atypical social communication and repetitive behavior that were present in the second year of life persisted in the third year of life.

Additionally, new red flags not present in the second year emerged in some children during the third year of life. These results may have important implications for better understanding how the characteristics of ASD unfold, which will enable earlier identification and intervention. This work was supported by two grants from the U.S. Department of Education, Office of Special Education and Rehabilitation Services (H324M010071 and H324C030112) and a grant from the U.S. Department of Education, Institute of Education Sciences (R305T010262). S2.5.6 OUTCOME AT 7 YEARS OF CHILDREN DIAGNOSED WITH AUTISM AT AGE 2. T. Charman*, E. Carter, A. Drew and G. Baird. Behavioural & Brain Sciences Unit. Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. t.charman@ich.ucl.ac.uk Twenty-six children diagnosed with autism at age 2 were re-assessed at ages 3 and 7 years. Although non-verbal IQ (NVIQ) for the group as a whole was stable across the 3 assessments, this masked considerable individual instability. Standard assessments at age 2 did not predict outcome at age 7 the same assessments conducted at age 3 did. A measure of rate of non-verbal communication at age 2 was significantly associated with language, communication and social outcomes at age 7. The pattern of autistic symptom severity varied over time by domain. On all measures group variability in scores increased with age. Caution is required when interpreting the findings from assessments of children with autism at age 2 years. At this age measures of non-verbal communicative function might be more informative than scores on standard psychometric tests. Predictive validity of assessments at age 3 years was greater. Variability in language, NVIQ and symptom severity increased over time. The trajectory of autism symptoms over time differed in different domains suggesting that they may be, at least in part, separable. Supported by grants from the Guys and St. Thomas Charitable Foundation and Cure Autism Now.

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Slide Session 2: Topic 6: Autism, Genes and

Enivronment S2.6.1 PRENATAL EXPOSURE TO ENVIRONMENTAL NEUROTOXICANTS DYSREGULATES DEVELOPMENT OF THE SEROTONERGIC SYSTEM: RELEVANCE TO AUTISM? J.M. Lauder. Dept. of Cell and Developmental Biology. Univ. NC School of Medicine Chapel Hill, NC. Autism is a complex neurodevelopmental disorder with strong genetic, and likely environmental, components. Evidence from animal and human studies indicates that multiple neurotransmitter systems may be altered in autism, including the serotonergic, GABAergic, cholinergic and glutamatergic systems. Candidate genes include neurotransmitter receptors, transporters, biosynthetic and metabolic enzymes, as well as transcription factors involved in neural development and patterning. Environmental neurotoxicants, like pesticides, interfere with neurotransmission by blocking receptors or enzymes that regulate biosynthesis or metabolism of neurotransmitter substances. These actions may make the developing nervous system especially vulnerable to prenatal exposures, since neurotransmitters play important roles in regulating key aspects of embryonic and fetal development. Vulnerability of developing neurotransmitter systems to prenatal neurotoxicant exposures is supported by recent evidence that organochlorines (dieldrin) and organophosphates (chlorpyrifos) dysregulate development of the serotonergic system in animal models. These studies bear relevance to human studies implicating abnormalities in the serotonergic system in autism. Genetic animal models that might be useful in dissecting potential gene-environment interactions in autism will be discussed S.2.6.2 LOSS OF NEUROPATHY TARGET ESTERASE IN MICE LINKS ORGANOPHOSPHATE EXPOSURE TO HYPERACTIVITY. C. Barlow (presenter), C.J. Winrow and J. Casida. The Salk Institute for

Biological Studies and the University of California at Berkeley. The interplay between genetics and environment and their contribution to early and late manifesting psychiatric disease remain unclear. In an effort to better understand how genetic alterations might predispose patients to developing symptoms while sparing other similarly exposed individuals, we studied the role of the gene Neuropathy Target Esterase (NTE) in contributing to the pathologies associated with exposure to organophosphates. NTE was originally described as an enzyme activity that could be inhibited by exposure to organophosphates found in nerve agents and specific classes of pesticides. We found that haploinsufficiency for an inactivating mutation of NTE in a mouse model led to marked increase in the susceptibility to the toxic effects of organophosphates (Winrow, et. al., 2003). In addition, characterization of the mice in the absence of organophosphate exposure showed that they exhibited symptoms consistent with hyperactivity. Finally, based on these findings we exposed normal mice to very low doses of organophosphates and found that a similar degree of hyperactivity was induced. These studies suggest that even extremely low levels of exposure can result in a neurobehavioral phenotype, particularly in individuals who might harbor mutations in the enzyme NTE. These and other recent findings that may help us understand the mechanism whereby these abnormalities occur will be discussed. 1. Winrow, C.J., Hemming, M.L., Allen, D.M., Quistad, G.B., Casida, J.E., Barlow, C. Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity. Nature Genetics 2003, 4, 477-485.

S2.6.3 RESPIRATORY INFECTION IN PREGNANT MICE CAUSES BEHAVIORAL AND CEREBELLAR DEFECTS IN THEIR OFFSPRING RESEMBLING THOSE IN AUTISM . P.H. Patterson* and L. Shi. Biology Division, California Institute of Technology, Pasadena, CA 91125.

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Maternal viral infection is implicated as a risk factor in autism. In developing an animal model based on this risk factor, we found that respiratory infection with influenza virus of pregnant mice at mid-gestation leads to behavioral abnormalities in the adult offspring. These include deficits in open field and novel object exploration, prepulse inhibition (PPI) and social interaction. These adult mice also display a type of neuropathology repeatedly found in autism - a deficit in Purkinje cells, specifically in lobules VI and VII of the cerebellum. We also occasionally see misplaced Purkinje cells in the white matter of lobule VII. This pathology may be related to the behavior of these mice, as Pierce and Courchesne (2001) found a strong correlation in autistic subjects between the extent of deficit in lobules VI-VII and the lack of exploration of novel objects. Also consistent with findings in autism, the offspring of infected mothers display abnormally small brains at birth, but by adulthood, these brains are larger than controls. The cause of these abnormalities is likely to be the maternal response to viral infection, as we find no evidence of virus in the fetus. Moreover, treatment of pregnant mice with dsRNA, which evokes an anti-viral-like immune response, also induces PPI abnormalities in the offspring. Supported by Ginger and Ted Jenkins, the Mettler Fund for Autism Research, the Stanley Medical Research Institute, the McKnight Foundation, Cure Autism Now, and the NIMH S2.6.4 WHAT CULTURE MODELS TELL US ABOUT MERCURY NEUROTOXICITY. M. Aschner* and J.L. Aschner**. Departments of *Physiology and Pharmacology, and **Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC. Mercury (Hg) is a pervasive global pollutant. Stringent control of man-made sources of mercury pollution will not eliminate human exposure to potentially toxic quantities, given its ubiquitous presence in the environment. Environmental exposure to mercury occurs primarily via the food chain due to accumulation of MeHg in fish. Latest US statistics indicate that 46 states have fish consumption advisories covering 40% of rivers, lakes and streams. Additionally, mercury is a common pollutant in hazardous waste sites. It is

estimated that 3-4 million children live within one mile of at least one of the 1,300+ active hazardous waste sites in the USA. The pathophysiology of MeHg and related organic mercury species has also been discussed within the context of exposure to thimerosal, a vaccine preservative. Traditionally, mechanistic studies on the effects of MeHg in the CNS have been limited to morphology, substrate uptake and macromolecular synthesis, differentiation, and changes in gene expression during development and adulthood, but its primary site of action has yet to be identified. Studies in our lab have begun to explore the role of posttranslational modifications by MeHg of the NOS and the COX-prostaglandin (PG) signaling pathways in search of unifying upstream mechanisms accounting for its ROS generation, mitochondrial dysfunction, changes in redox potential, macromolecule synthesis, and cell swelling. Studies on altered post-translational modification of NOS and COX-PG by Hsp90 suggest that MeHg interferes with Hsp90 chaperone function resulting in altered cellular homeostasis and neurotoxicity, providing broad biological implications for mechanisms associated with abnormal development and neurodegeneration. Supported by NIEHS 07331 S2.6.5 GABAa RECEPTOR DEFICIENCY SIGNIFICANTLY POTENTIATES EXCITOTOXICITY OF NONCOPLANAR PCB 170 IN THE ACUTE HIPPOCAMPAL SLICE PREPARATION. K.H. Kim and I.N. Pessah*. Center for Children’s Environmental Health and Disease Prevention and M.I.N.D. Institute, University of California, Davis, CA 95616. Evidence is mounting that exposure to non-coplanar PCB's is associated with significant changes in locomotor activity, spatial learning and memory in humans and animal models. In the current study, PCB 170-induced changes in synaptic transmission of rat hippocampal slices were monitored by electrophysiological measurements using the MED64 electrode array system. Field excitatory postsynaptic potential (fEPSP) was evoked by single pulse stimulation of Schaffer Collateral/commissural fibers at striatum radiatum of the CA1 region in the hippocampus. Following exposure to 10-1000 nM PCB 170, time-dependent

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changes in the slope and amplitude of fEPSP were seen, with phases of enhancement and subsequent depression. To investigate the contribution of inhibitory neurons in the actions of PCB 170, hippocampal slices were pre-treated with the GABAa receptor antagonist, picrotoxin (PTX, 100 �M). Pre-treatment with PTX resulted in negligible change in EPSP slope elicited by single pulse stimuli. Importantly PCB170 (1-100 nM) introduced in the presence of GABAa blockade enhanced EPSP slope (20-300%) revealing a significant facilitation of synaptic transmission. Non-coplanar PCBs therefore influence both excitatory and inhibitory pathways in CA1 that can mask their potent effects. These results demonstrate that blockade of inhibitory inputs with PTX can unmask the potent actions of ortho-substituted PCB 170 toward facilitating excitatory transmission. Moreover the measured effect of PCB 170 on neuroplasticity is a summation of actions on inhibitory and excitatory pathways in hippocampus, which may stem from a common mechanism. Significance of these results to polymophisms within GABAa receptor beta3 subunit recently linked to autism susceptibility will be discussed. Supported by NIEHS 0P01 ES11269.

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Slide Session 3 Topic 1: Face Processing II S3.1.1 FACE PROCESSING IN AUTISM: IS THERE PLASTICITY IN BRAIN ACTIVATION? S. Faja, E. Aylward, R. Bernier, M. Bloomquist and G. Dawson*. University of Washington, Box 357920, Seattle, WA 98185. Typically developing adolescents and adults process faces in a way that uniquely differs from object perception (i.e. holistically, encoding configural information) using specifically devoted brain structures (e.g. the face fusiform gyrus). Recent evidence suggests that face processing in individuals with autism may not fully differ from objects (e.g. a lessened face inversion effect, less reliance on holistic processing, increased attention to features such as the mouth) and that the face fusiform region is weakly or not activated in response to faces, with more diffuse activation shown in surrounding regions (e.g. the inferior temporal gyrus). The present study investigates the effect of face-specific training, based on Gauthiers expertise protocol with autism specific modifications, on the face processing behavior and brain activation of 5 individuals (aged 13-32) with HF autism compared with 4 untrained individuals with autism. Behavior was examined using experimental measures of holistic processing and of configural sensitivity. Activation was measured using fMRI of passively viewed faces & cars and actively viewed upright & inverted faces. All trained individuals achieved the behavioral criterion of expertise established in the literature (Tanaka & Taylor, 1991). The trained group showed significantly improved sensitivity to configural information compared with untrained controls on a 96 item match-to-sample test, t(7)= 2.46, p=0.044, but did not differ on the measure of holistic processing. Neuroimaging results are currently being analyzed and will be reported. Supported by Cure Autism Now Foundation and NIMH U19 HD35465. S3.1.2 NORMAL ACTIVATION OF FUSIFORM GYRUS IN ADOLESCENTS AND ADULTS WITH

AUTISM DURING VIEWING OF FAMILIAR FACES. E. Aylward, R. Bernier, K. Field, A. Grimme and G. Dawson*. University of Washington, Box 357115, Seattle, WA 98185. Both clinical observation and research studies have demonstrated that individuals with autism often have difficulty in the ability to recognize faces. The fusiform gyrus is the region of the brain that is activated when normally developing adolescents and adults view pictures of faces. It has been argued that this region is also activated by visual stimuli with which the viewer is particularly familiar. Previous functional MRI (fMRI) studies have demonstrated that the fusiform gyrus is not activated when individuals with autism view faces; instead a more lateral brain region that is generally associated with object perception, the inferior temporal gyrus, is activated. The current study investigated activation of the fusiform gyrus and inferior temporal gyrus in 11 high-functioning adolescents and adults with autism and 10 matched controls when they viewed faces as compared with cars. As previously demonstrated, the area of activation was more lateral in individuals with autism than in controls. However, when individuals with autism viewed a familiar face (e.g., their mother’s face), as compared with cars or an unfamiliar face, the fusiform was activated. These results suggests that lack of normal activation of the fusiform gyrus in individuals with autism in response to viewing faces may be due to their lack of familiarity with this type of visual stimulus, rather than inherent abnormal functioning of this brain region. Supported by Cure Autism Now Foundation, and NIMH U54MH066399. S3.1.3 FACE PROCESSING IS ALTERED IN AUTISM FAMILIES: BEHAVIORAL AND ERP EVIDENCE. G. Dawson*, S. Webb, S. Faja and M. Paul. University of Washington, Box 357920, Seattle, WA 98185. Research indicates that individuals with autism have difficulty processing and forming memories for faces. It is unknown whether or not this deficit extends to first degree relatives. The present study investigates whether adults, who have at least two

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children with autism (Family Group), exhibit the same behavioral performance and ERP activity when perceiving human faces as typical adults, who do not have a child with autism (Control Group). Behavioral measures consisted of the Broader Phenotype of Autism Scale, face and object memory tasks, and the Reading the Mind in the Eyes task. ERPs were recorded to upright and inverted faces and chairs. On the face memory task, there were no differences in performance between the two groups. On the ERP, both groups replicated previous N170 results: greater amplitude responses to upright faces compared to upright chairs; greater amplitude responses to inverted faces than upright faces; and faster response to upright than inverted faces. However, the Family Group did not demonstrate right hemisphere lateralization of face processing; the Control Group demonstrated greater responses in the right than left. These preliminary results suggest that adults who have two children with autism display different topographical brain responses to faces than those of adults who do not have a child with autism. Further analyses will examine the relation between topographical distribution of ERP responses, behavioral assessments of face recognition, and broader phenotype traits. Support: This research was supported by a grant from NICHD and NIDCD (U19 HD35465). S3.1.4 ELECTROPHYSIOLOGICAL EVIDENCE OF DELAYED NEURAL PROCESSING OF FACES IN CHILDREN WITH AUTISM S. Webb, R. Bernier, J. Shook, M. Paul and G. Dawson. University of Washington, Box 357920, Seattle WA, 98195. Neuroimaging and behavioral studies indicate that autism is characterized by fundamental impairments in social cognition. This may be evident by a failure to process faces and to form memories for faces. For example, when examining the developmental precursor of the face specific N170 ERP (termed “prN170”), young children with autism spectrum disorder (ASD) show significantly slower ERP responses to faces (Webb et al., 2003), and fail to show differential responses to a familiar versus novel face (Dawson et al., 2002). Studies also demonstrate behavioral impairments in face

recognition in children with ASD. To elucidate the links between face processing and face recognition, we compared face and object processing using behavioral measures and event related potentials (ERPs) from six-year old children with autism (ASD), developmental delay (DD), and typical development. ERPs were recorded to familiar and novel faces and objects. Behavioral measures consisted of adaptive behavior, language, and face and object memory measures. On the face memory task, typically-developing children performed significantly better than children with ASD and DD. On the ERP task, all children displayed greater prN170 amplitude to the familiar as compared to the novel face. The prN170 latency to faces was significantly faster in the typical group than the DD and AUT group. Further analyses will examine the relation between speed of face processing, behavioral assessments of face recognition, and social abilities. Support: This research was supported by a grant from NICHD and NIDCD (U19 HD35465) S3.1.5 THE FEFA: A COMPUTER-BASED PROGRAM TO TEST AND TO TEACH THE RECOGNITION OF FACIAL AFFECT . F. Poustka, S. Feineis-Matthews and S. Bölte. Department of Child and Adolescent Psychiatry, J.W.Goethe-University, Frankfurt/M, Germany. The endophenotype of autism includes neuropsychological deficits, for instance a lack of facial affect recognition. In this study, we report the development and evaluation of a computer-based program to test and to train the ability to identify basic facially expressed emotions called FEFA (�Frankfurter Test und Training des Erkennens von fazialem Affekt). The two tasks (emotion in faces/eyes) of the facial affect recognition test showed good psychometric properties in a sample of N = 35 normative individuals (internal consistency: rtt=.91-.95; retest reliability: rtt=.89-.92). To evaluate the efficacy of the training module of the FEFA in a clinical sample, five adolescent or adult subjects with high-functioning autism or Asperger-syndrome received computer-based facial affect recognition training while additional five matched subjects served as control group. The training was conducted for five weeks, consisting of two hours training a

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week. Pre-post, the trained individuals improved significantly on both tasks of the affect recognition test (Z>1.9, p<.04). Despite an unknown generalization into everyday life other areas of function, the results support the usefulness of the program to teach the detection of facial affect. S3.1.6 FACE PROCESSING IN HIGH FUNCTIONING AUTISTIC ADULTS: A LOOK INTO SPATIAL FREQUENCIES AND THE INVERSION EFFECT. C. Rondan 1,2 and C. Deruelle 1. 1 Institute of Physiologic and Cognitive Neurosciences, CNRS, Marseille, France & 2 Laboratory of Psychology and Neurocognition, UMR 5105, CNRS, Grenoble, France This research was aimed at exploring possible abnormal face processing strategies in high functioning adults with autism (HFA). Subjects were to match faces (upright or upside down) or chairs filtered in high (HSF, local processing) and low spatial frequencies (LSF, holistic processing) to non-filtered images. Results show that contrary to controls the autistic group did not show a face inversion effect but that they presented the typical LSF advantage when matching faces. We suggest that the HFA population may de deficient in some (LSF processing) but not all (relationships between parts) forms of configural processing. Slide Session 3: Topic 2: Neuropsychological

Processes S3.2.1 REDUCED LEFT INFERIOR FRONTAL AND ENHANCED OCCIPITAL ACTIVATION DURING SEMANTIC DECISION IN AUTISM: AN fMRI STUDY. M.S. Gaffrey (1), N. Kleinhans (2), F. Haist (3), and R-A. Müller (1,4)*. (1) Dept. of Psychology, San Diego State University; (2) JDP Clinical Psychology; Depts. Of (3) Psychiatry and (4) Cognitive Science, University of California, San Diego, CA 92120/92093. Although a few behavioral studies have suggested atypical semantic organization in autism (1), little functional imaging evidence is available.

The current study examined hemodynamic effects during semantic category decision. Eight high-functioning autistic men and 9 gender, handedness, and age-matched controls were studied using fMRI. Subjects determined via button press response whether visually presented words belonged to a target category (tools, emotions, colors). The control condition required target letter detection in unpronounceable non-word letter strings. Correlation with hemodynamic ideals revealed extensive clusters of significant activation for semantic decision in left the inferior frontal gyrus and sulcus (areas 44 through 47) for the control group. Corresponding activation in the autism group was much more limited and only seen in left inferior frontal sulcus (areas 44/46). However, autistic patients showed significant greater activation than controls in the right visual cortex (area 18). Our findings may indicate reduced left inferior frontal participation in lexicosemantic processing in autism, possibly consistent with previous anatomical findings (2). Atypically robust occipital activation in autism further suggests an important role of nonlinguistic components (possibly visual imagery) during semantic decision. (1) Dunn et al., Child Neuropsy 2:99; (2) Herbert et al. 52:588. Supported by NIDCD 1R01-DC06155 S3.2.2 PERCEPTUAL AND NEUROPHYSIOLOGICAL MEASURES OF AUDITORY FUNCTION IN CHILDREN WITH AUTISM DISORDER: AN MEG INVESTIGATION . N.M. Gage*, P. Fillmore, L. Isenberg, L. Mays and A. Spence. Univ of Calif, Irvine, Irvine, CA 92697 Language deficits combine with abnormal sound sensitivity to implicate auditory system dysfunction in autism disorder (AD). We combine behavioral and neuroimaging techniques to investigate auditory function in AD children (9-11yrs) and healthy age-matched controls. Behavioral experiments: Frequency, Gap, Vowel (V), Consonant-Vowel (CV), & Vowel-Consonant-Vowel (VCV) Discrimination to evaluate perceptual acuity for speech and non-speech contrasts. Identical stimuli were presented during Magnetoencephalography (MEG) recording. Latency of the M100 component, localizing to auditory cortex, was measured. Behavioral Results:

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Frequency Discrimination thresholds were significantly higher in AD children (Difference Limen (DL): .30-.60) vs. Controls (DL: .01-.05). Gap Discrimination thresholds were higher in AD children (7.0 ms) vs. Controls (2.8 ms). AD children performed at similar levels as Controls in V Discrimination, however at lower levels in CV and VCV conditions. MEG Results: M100 latency was prolonged (30-40 ms) in both groups vs. adults. AD: dynamic range of M100 latency modulation by Frequency contrasts (250-2000Hz) was reduced (10 ms) in AD vs. controls (17 ms), perhaps reflecting a compressed range of frequency encoding. M100 modulation by Gap duration was also reduced in AD vs. controls, although high level of variability limited interpretation of results. Heightened perceptual thresholds combined with reduced M100 latency modulation in AD children may relate to language impairment in AD. Results provide complementary measures of perceptual acuity and neural discrimination in AD. Supported by M.I.N.D. Institute & NAAR (NG). S3.2.3 DIMINISHED SEROTONIN RECEPTOR FUNCTION: A POTENTIAL ENDOPHENOTYPE OF AUTISM. J. Goldberg 1, P. Szatmari 2 and L. Zwaigenbaum 2. 1c'o Department Psychiatry and Behavioral Neurosciences, Chedoke Child and Family Centre, HHS, Hamilton. 2 McMaster University, Hamilton ON, Canada, L8N 3Z5 BACKGROUND Autistic Disorder (AD), a severe developmental disorder, has an unknown etiology. Genetic factors and the neurotransmitter serotonin (5HT) have been implicated in the pathogenesis of this complex disorder. Moreover, 5HT function has been suggested as a possible an endophenotype of the autism spectrum of disorders (ASD). Against this background, we investigated central 5HT function as a potential endophenotype of ASD by examining parents of probands with AD using 18F Setoperone Positron Emission Tomography (SETOPERONE PET). METHODS 19 Parents and 20 controls underwent 18F SETOPERONE PET, a reliable and valid in-vivo method for measuring central 5HT2A receptor function. The ratio of 18F Setoperone activity in a specific brain region (S) and its activity in the

cerebellum (C), which is termed the binding potential (BP) is related to the Binding Density (BD) for that specific region. RESULTS BP’s in 24 brain regions were compared in parents and controls. The BP was significantly lower in 14 out of 24 brain regions. Given the multiple comparisons and our apriori hypothesis, that 5HT2A receptor density would be lower in the parents, we used the Wilcoxon Signed Rank Test to show that when the brain regions are viewed collectively, the BP is lower (using a nominal p value of 0.05) in parents as compared to controls (z = -4.170). CONCLUSION This is the first study to provide evidence of reduced 5HT2A receptor Binding Potential in the brain of parents of children with autism, which is consistent with previous studies that showed reduced platelet 5HT2A receptor binding density in autistic probands and in some of their parents. However, before reduced brain 5HT2A receptor density can be viewed as an endophenotype of ASD, this finding must also be shown in proband. S3.2.4 REDUCED MODULATION OF COVERT ORIENTING REFLEXES IN HIGH FUNCTIONING ADOLESCENTS WITH AUTISM. G. Iarocci, J.A. Burack*, J.T. Enns, B. Randolph, and L. Mottron. Department of Psychology Simon Fraser University 8888 University Drive Burnaby, British Columbia V5A 1S6 Method. High functioning adolescents with autism and typically developing adolescents matched for CA (approximately 15 years) and IQ (approximately 108) were administered a simple detection task in which the effects of the combination of predictive arrow cues and non-predictive flash cues within a single trial permitted the investigation of the coordination of reflexive and voluntary processes of visual orienting. Results. No group differences were found on either the reflexive or the voluntary aspects of orienting when these were examined separately. However, group differences were found when these components needed to be coordinated for effective target processing. Participants with autism were less able to flexibly coordinate competing voluntary and reflexive demands in order to execute a task-relevant response.

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Conclusions. These findings are consistent with previous reports of intact reflexive visual orienting in response to peripheral cues among persons with high functioning autism (Iarocci & Burack, in press), but inconsistent with reports of deficient disengaging or voluntary orienting in this population (Burack, Enns, Stauder, Mottron, & Randolph, 1997; Singer-Harris et al., 1999; Townsend, Courchesne, & Egaas, 1996; Wainright-Sharp & Bryson, 1993). Deficiencies in performance were apparent when persons with autism were required to exercise executive control in order to modulate their reflexes. Thus, the notion of a general voluntary orienting deficit needs to be re-examined. S3.2.5 PREFRONTAL-LIMBIC DYSFUNCTION IN AUTISM. K.A. Loveland, J. Bachevalier and D.A. Pearson. Univ Texas Med Sch Houston TX 77030. Children and adolescents VIQ > 64 (Autism n=53; Controls n=44) were compared on three neuropsychological tasks: Delayed Spatial Alternation (dorsolateral prefrontal cortex); Spatial Span (hippocampus); and Emotion Recognition/Delayed Non-match to Sample (amygdala orbitoprefrontal cortex). Delayed Spatial Alternation. Subjects learned to choose one of two stimuli alternately to receive a hidden reward. There was a significant effect of group overall (p=.016). Controls had fewer errors (p=.005) and fewer trials to criterion (p=.008). Memory Span. The spatial memory task Spatial Span (30 and 5 sec delays) was presented with its control task, Object Span. Subjects identified the newest item by location alone. The effect of group on mean trials to criterion was highly significant (p = .003). Both groups performed well on Object Span, however both Spatial Span conditions differed significantly between groups (Controls > Autism) (p=.001). Facial and Emotion Recognition. The subject learns that the reward will be hidden under the new stimulus in the pair. Three conditions are presented: Object Recognition (control , Facial Identity Recognition, and Emotion Recognition. Only the Facial Identity (p=.016) and Facial Emotion conditions (p=.047) were significantly different by group (Controls > Autism).

Compared with well matched control subjects, subjects with autism performed well on discrimination and memory for objects, but not when stimuli were facial or emotional, or when spatial location was the primary cue. Executive functioning was also impaired in the autism group compared with controls. S3.2.6 REDUCED OCCIPITO-FRONTAL FUNCTIONAL CONNECTIVITY DURING VISUOMOTOR PERFORMANCE IN AUTISM. M.E. Villalobos, A. Mizuno, B.C. Dahl and R-A. Müller *. Brain Development Imaging Lab, San Diego State University, San Diego, CA 92120. Previous autism studies (1) including our own fMRI studies (2) indicated abnormalities of the visual dorsal stream, which may underlie impaired joint attention (3). However, no study has yet investigated functional connectivity of the autistic brain during visuomotor processing in the dorsal stream. We applied a technique for functional connectivity mapping previously validated by several groups (4) Using fMRI, we studied 8 high-functioning autistic men and 8 handedness and age-matched controls. A visually prompted 6-digit sequence was performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal covariance with the mean time series in bilateral visual area 17. Normal adults showed significant functional connectivity with bilateral parietal, left pericentral, and dorsolateral prefrontal cortices (DLPFC). Autistic subjects showed left lateralizing effects in parietal, pericentral, and premotor cortices. Functional connectivity between area 17 and area 10 in DLPFC - prominent in controls - was absent in autistic patients. These results suggest that in autism connectivity along the dorsal stream is mostly functional during visuomotor coordination, but reduced in prefrontal cortex, possibly accounting for impaired visuomotor coordination and learning. (1) Spencer et al., NeuroReport 11:2765; (2) Müller et al., Am J Psychiat 160:1847; (3) Williams et al., Neurosci Biobehav Rev 25:287; (4) e.g., Xiong et al. Hum Brain Mapp 8:151. Supported by NIDCD 1R01-DC06155

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Slide Session 3: Topic 3: Gentetics III S3.3.1 EVIDENCE A NONVERBAL COMMUNICATION AUTISM ENDOPHENTOYPE IS LINKED TO CHROMOMSOME 3q25 AND ASSOCIATED WITH THE NEUROLIGIN-1 GENE IN THAT REGION. G. Chen, J.L. Stone, N. Kono, S.F. Nelson, D.H. Geschwindand and R.M. Cantor. Depts. of Human Genetics, and Neurology, UCLA School of Medicine, Los Angeles, CA 90024 Twin studies of autism indicate a high heritability; however, the major genes remain to be identified, providing support that it is genetically complex. We have been analyzing quantitative endophenotypes to identify heritable autism traits and map genes contributing to aspects of this disorder. A quantitative trait derived from items in the Autism Diagnostic Instrument - Revised (ADI-R) that addresses nonverbal communication skills was applied to the Autism Genetic Resource Exchange (AGRE) sample of affected sibling pairs. A Haseman-Elston QTL analysis of the genome scan data and this trait on concordant narrow-diagnosis sibpairs (N=259) implicated a region on chromosome 3 (3q25) with a LOD score of 2.1. Analyses of 14 SNPs located within the positional candidate gene, Neuroligin-1 (NLGN1), provide evidence of association (p<0.005) with the trait. While linkage was not seen, evidence for association with narrow autism was also observed (p < 0.05). Neuroligins (NLGN) have been shown to localize at postsynaptic neural junctions (particularly excitatory synapses), where they may interact with other proteins such as PSD-95 and NMDA-R1 during synaptogenesis in the young brain. Previous studies implicate NLGN3 and NLGN4 on the X-chromosome in the broad autism phenotype. These analyses suggest that NLGN1 may also play a role in the pathology of autism. This work was supported by NIH grants R01 MH64547 and T32 HG02536. S3.3.2 A GENETIC STUDY OF THE NEUROCOGNITIVE DEFICITS IN AUTISM. J. Hallmayer, D. Wong, A. Maley, W. Hill, D. Bishop

and M. Maybery. Department of Psychiatry, Stanford University School of Medicine, Department of Psychology, University of Western Australia (UWA), and School of Psychiatry and Clinical Neurosciences, UWA. Family and molecular studies failed to show a clear relationship between the clinical manifestation of autism and a specific genotype. Different aspects of the autism phenotype may be influenced by different loci. Identification of individuals based on indicators more proximal to the genetic liability may result in more coherent genetic results. In this family study we targeted specifically four areas of neurocognitive functioning shown to differentiate individuals with a pervasive developmental disorder (PDD) from controls: Theory of Mind (ToM), Executive Functioning (EF), Central Coherence and Language. All available first-degree relative of probands diagnosed with a pervasive developmental disorder in 80 families as well as 50 control families were assessed with a complex test battery (15 different tests in addition to the Autism Diagnostic Interview). The Autism Spectrum Quotient identified relatively high rates of autistic-like traits in parents of children with a PDD. Differences between parents in proband and control groups were seen only on the social skills and communication scales. On neither phonological measure differed relatives of probands from control relatives. Phonological processing deficits are not part of the broader phenotype. Two measures of EF, but none of the ToM variables, showed differences between probands and siblings. Only EF measures showed a relationship with behavioral measures of PDD. These results lend support to the hypothesis that impairments in EF are more primary and may hold more explanatory value for genetic studies. S3.3.3 STRATIFICATION OF AUTISM FAMILIES BASED ON SEX OF AFFECTED CHILDREN IDENTIFIES DISTINCT LINKAGE REGIONS . J.L. Stone, B. Merriman, R. Cantor, A. Yonan, AGRE Consortium, T.C. Gilliam, D.H. Geschwind and S.F. Nelson*. UCLA Human Genetics and Neurology departments, Los Angeles, CA 90095.

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Autism Spectrum Disorder (ASD) is marked by a profound bias in the gender of affected individuals. While the prevalence of ASD is estimated at 1/1000 in the general population (Folstein et al 2001), the ratio of affected males to females is 4-10:1 (Miles et al 2000, Frombonne E. 1999). This male bias is consistent across many studies and is more striking in higher functioning individuals with autism. It has been suggested that to produce an affected female requires a heavier genetic load of susceptibility genes (Tsai et al 1983). In order to test if a more homogeneous genetic group could be identified based on sex of the affecteds, we used genome scan data of Yonan et al (2003), and subdivided affected sibling pair families into two groups based on the sex of their affected children; 138 families contained only affected males while 108 families contained at least one affected female. Reanalysis of the genome scan data indicated two regions of the genome highly skewed due to the sex of affected children. First, there was stronger evidence of linkage to 17q11 (MLS 4.7) in families with affected boys only. The chromosome 17q region has been previously implicated by Yonan, et al. The shift in linkage score by sex-stratification is non-random (p=0.01). Second, 4q31-q34 was linked in families with at least one affected girl (MLS 2.8, genome-wide p<0.01), a region not implicated in the initial genome scan. These results support the notion that genetic variants which predispose to autism in boys and girls may have profoundly different effects in developing male and female brains. S3.3.4 INTERGENERATIONAL TRANSMISSION OF AUTISTIC TRAITS: A STUDY OF TWINS AND THEIR PARENTS. J.N. Constantino*, and R.D. Todd*. Social Developmental Studies Program, Washington University School of Medicine, St. Louis, MO 63110, USA. Autistic Disorder (AD) is an increasingly common, oligogenic condition in which fully affected individuals rarely reproduce. It is characterized primarily by deficiency in the capacity for reciprocal social behavior (RSB). When measured as a quantitative trait in the general population, deficiency in RSB exhibits a genetic structure highly similar to that observed for clinically-defined AD. Furthermore,

RSB deficits whose severity falls below the threshold for a clinical diagnosis of AD have been shown to aggregate in the family members of autistic probands. Using a quantitative measure of RSB, the Social Responsiveness Scale (SRS), we assessed 285 pairs of twins (by maternal report) and their parents (by spouse report). We observed intergenerational associations between the scores of parents and their children, the magnitude of which (Pearson�s coefficient of correlation on the order of 0.45) was similar to what has been observed between non-identical twins. Parameter estimates for genetic and environmental influences on SRS scores of fathers and mothers were highly consistent with those derived for male and female twins. In addition, there was evidence for preferential mating explaining up to 30 per cent of the variation in parent SRS scores. Such assortative mating may play a role in maintaining or increasing the prevalence of AD, and has important implications for genetic studies of social development in children. S3.3.5 SCREENING FOR THE AUTISM SPECTRUM IN A STATEWIDE TWIN SAMPLE. H.H. Goldsmith, M.A. Gernsbacher, E.K. Kees and C.A. Van Hulle. Waisman Center & Department of Psychology, Univ. of Wisconsin, Madison, WI. 53706. Inferences about the degree of genetic influence on individual differences in the autism spectrum depend crucially on the relative risk to siblings and the differential concordance of monozygotic (MZ) vs. dizygotic (DZ) cotwins. The latter is unknown (for the spectrum), but accurate information would affect the plausibility of various linkage approaches. In addition, population-based twin studies can address possible over-representation of twins among ASD cases. Beginning with 1997 births and working from all state birth records, we screened two-year old twins (mean age 27 mos.) statewide with a 20-item instrument designed to tap early signs of autism spectrum. Slightly >1% of scores lay beyond the tail of a normal distribution, and another 3-4% were in the tail of a slight skew toward a high screening score. Data from over 1600 children have been analyzed in ongoing screening. For a broad upper

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5% threshold, the pair-wise concordance rates were MZ=57% and DZ=25%. A more extreme threshold lowered only the DZ concordance rate. Examining only social or communication domains appeared not to affect concordance rates. We also report analyses for the screening instrument for the entire sample (i.e., considering the view of an "autism trait" in the population). In addition to expanding the sample, we have begun to identify subsequent clinical cases in the entire distribution of scores, with the expected concentration among those with high screening scores. Funded by a grant from the National Alliance for Autism Research and by NIMH (R01-MH59785), H. H. Goldsmith, PI. Slide Session 3 Topic 4: School Age

Intervention S3.4.1 SYSTEMIZING EMPATHY: TEACHING ADULTS WITH ASPERGER SYNDROME TO RECOGNIZE COMPLEX EMOTIONS. O. Golan and S. Baron-Cohen*. Autism Research Centre, Departments of Experimental Psychology and Psychiatry, Cambridge University, 18b Trumpington Road, Cambridge, CB2 2AH, U.K. Adults with Asperger Syndrome (AS) can recognize simple emotions and pass basic theory of mind tasks, but have difficulties recognizing more complex emotions and mental states. This might underlie their social difficulties. The study evaluates a new computer-based intervention, named Mind Reading (www.jkp.com/mindreading), and its effectiveness in teaching individuals with AS to recognize emotions. Three intervention groups for participants with AS and two control groups were assessed (n=15 in each): Group 1 used Mind Reading at home for a period of 10 weeks. Group 2 took a 10 week social skills course. Group 3 used the software at home for 10 weeks and met weekly with a tutor to enhance consolidation. Group 4 comprised participants with AS who had no intervention. Group 5 comprised typically developed controls. All groups were matched to each other on age and IQ. Participants with AS were assessed at week 1 and week 10 on their ability to recognize

emotions in faces and voices at two levels of generalization (close and distant). Results are described and discussed in terms of the ability to systematically teach emotion recognition to adults with AS and to generalize from taught to novel material. This study was supported by the National Alliance for Autism Research, The Corob Charitable Trust and the Cambridge Overseas Trust. S3.4.2 THE EFFECTIVENESS OF RELATIONSHIP DEVELOPMENT INTERVENTION IN REMEDIATING DEFICITS IN INTER-SUBJECTIVE ENGAGEMENT IN AUTISM-SPECTRUM CHILDREN. S.E. Gutstein. The Connections Center for Family and Personal Development, Houston, Texas 77025 Relationship Development Intervention (RDI) is a new treatment approach, specifically designed to provide parents with tools to remediate their child�s deficits in Inter-subjective Engagement - a core social-emotional impairment in autism. RDI is based on systematically replicating the implicit processes employed by parents and their typically developing children leading to the child’s eventual competence as an active participant in dynamic, emotion-based systems. RDI is a developmentally staged, explicit and sequenced clinical intervention, modified to address the unique obstacles presented by children in the autism spectrum. Parents are trained to implement activities and exercises based upon these methods under the consultation of a trained provider. In a preliminary evaluation of RDI’s effectiveness, seventeen children whose families participated in RDI were compared to 14 children receiving other therapies. Changes in the ADOS and school placement were used as primary outcome measures. Children in the non-RDI group received appreciably more intervention than the RDI group. However, only children in the RDI group demonstrated significant improvement in ADOS scores, ADOS diagnostic categories and more effective functioning in typical classrooms. Results, while preliminary, provide strong early support for RDI as a powerful intervention tool for treating the

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social-emotional deficits of children in the autism spectrum. S3.4.3 PROPOSED USE OF TWO-PART INTERACTIVE MODELING TO ENGENDER EMPTHAY IN CHILDREN WITH AUTISM . D. Sherman and I.M. Pepperberg. Psychol. Dept, Brandeis University, Waltham, MA 02454; MIT School of Architecture and Planning, Cambridge, MA 02139; New-Found Therapies, Monterey, CA 93940. Many behavior modification/intervention programs for children are based on operant procedures developed for animal subjects, but few use modeling procedures in which one student observes interactions between two proficient trainers. We show how such procedures, which successfully trained Grey parrots (Psittacus erithacus) to produce and comprehend elements of human language, have be adapted for use with autistic children to enable them to engage in different levels of empathetic interactions and to respond to others’ emotions and needs with varied voice and behavioral patterns. S3.4.4 A COGNITIVE-BEHAVIORAL INTERVENTION WITH PARENT COACHING FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS. M. Solomon, Ph.D. and B. Goodlin-Jones, Ph.D. Department of Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UCDHS, 2825 50th Street, Sacramento, CA 95817 Sponsor: Children’s Miracle Network* Autism spectrum disorders affect approximately 1 in 200 children. Studies have found that some children with autistic spectrum disorders have difficulties transitioning between activities, verbally expressing and modulating affect, and tolerating frustration when required to take another person’s lead in conversation or play. These challenges then may produce externalizing behavior problems and oppositionality. In general, there are few evidence-based interventions for children with ASDs (exceptions exist, e.g.Ozonoff (1995); Solomon, Goodlin-Jones

& Anders, (in press)). This report involves the use of a manualized and empirically supported 12-week intervention program called Parent-Child Interaction Therapy (PCIT; Mc Neill & Himbree-Kigin, 1995). PCIT has proven to be successful with children with oppositional, conduct, and hyperactivity disorders. A wait-list control group design was employed for comparison purposes. We describe preliminary success with children with ASD and required adaptations to the therapy for this clinical population. PCIT sessions have targeted deficits in behavioral compliance, improving social skills, scaffolding language development, increasing behavioral flexibility, and improving emotional awareness and expression. In PCIT, therapists work closely with the parents using bug-in-the ear technology and a two-way mirror. Significant results on children’s measures of psychological well-being as well as teacher and parent reports of behavioral problems will be described. S3.4.5 EFFICACY OF FATHER-FOCUSED PARENT TRAINING FOR FATHERS OF CHILDREN WITH AUTISM . J.M. Winter* and L. Schreibman. Autism Research Laboratory, Univ. of California, San Diego, Dept. of Psychology 0109, La Jolla, CA 92093-0109. Father participation in training programs for parents of children with autism is minimal and has not increased over time (Budd & O�Brien, 1982). Fathers who have not participated in training have reported a lack of time, find the times parent education is offered to be inconvenient, and report that incorporating recreational activities would increase the likelihood of their participation (Winter & Schreibman, 2002). Taking these needs into consideration, a parent training intervention was designed specifically for fathers. In the present study, this father-focused (FF) education program was compared to a standard (ST) program (how training is typically delivered to parents in a research setting). This study employs a single subject, multiple baseline design. In both the ST and FF packages, fathers receive 10 weeks of training in Pivotal Response Training (PRT), a naturalistic behavioral therapeutic technique aimed at increasing language and play skills by targeting the

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child’s motivation. Data have been collected from 3 fathers and their children with autism (ages 2-4) thus far. Preliminary findings suggest that fathers are more likely to participate in the FF package than the ST package. Also, children in the FF package have evidenced greater change in target behaviors than children in the ST package; high levels of cancellations seen in the ST package may negatively impact the child’s behavior changes and the parent’s effectiveness in implementing the therapy. The findings obtained so far suggest that a father-focused training program can be beneficial to both the child and the quality of the father-child interaction. Slide Session 3: Topic 5: Biological Aspects in

Early Development S3.5.1 ACCELERATED HEAD GROWTH DURING EARLY DEVELOPMENT AND RISK FOR AUTISTIC DISORDER. Y.A. Dementieva 1,2, D.D. Vance 1, S.L. Donnelly 1, C.M. Wolpert 1, S.A. Ravan 3, R.K. Abramson 3, H.H. Wright 3, M. Cuccaro* 1, 4. 1Center for Human Genetics, Duke University Medical Center, Durham, NC 27710. 2Division of Math. & Applied Science, Marshall University, Huntington, WV 25755. 3W.S. Hall Psychiatric Institute, University of South Carolina, Columbia, NC 29208. 4Division of Psychiatry, Duke University. Medical Center, Durham, NC 27710 Macrocephaly is a consistent physical finding in autism. The current study proposes that it is not macrocephaly but abnormal acceleration in head growth during early development that is associated with autism. Head circumference (HC) data was examined in 245 individuals with autism. Macrocephaly (HC > 97%) was found in 19% of the sample. Abnormal acceleration in head growth (an increase of > 25 points in HC percentile values) was found between two consecutive measurements in 35% of individuals with multiple HC records. A significant percentage showed an abnormal increase in head size between 1 to 2 months. Individuals with accelerated head growth in early childhood showed

significantly greater adaptive functioning and a trend toward less social impairment. The current study supports recent findings of abnormal acceleration in head growth in autism. The results from this sample of individuals with autism point to a clear abnormal acceleration during the first and second months of life, suggesting that this acceleration may serve as an early indicator of risk for autism development. S3.5.2 PATHOLOGICAL BRAIN OVERGROWTH LEADS TO REDUCED INTERHEMISPHERIC CONNECTIVITY. J.D. Lewis and E. Courchesne. Center for Autism Research, Children's Hospital Research Center, San Diego, CA, 92037 The clinical onset of autism appears to be preceded by a period of abnormally accelerated brain growth. Findings from comparative neuroanatomy and from developmental neuroscience motivate the hypothesis that this abnormal growth trajectory will give rise to a deviant pattern of cortico-cortical connectivity; specifically, a reduction in the number of long-distance connections such as those that comprise the corpus callosum. Interhemispheric conduction delay is proportional to brain size, and so brain overgrowth early in development will provide increased impetus to reduce interhemispheric communication, and so to reduce the corpus callosum. This prediction was tested by measuring the head circumferences and the corpora callosa from the MRIs of individuals with autism spectrum disorder for whom medical records were sufficient to approximate a growth trajectory, and for whom longitudinal MRIs were available. The relation between rate of growth and relative corpus callosum size was found to be significant for the anterior portion of the callosum in the earlier MRIs; and in the later MRIs the relation between head circumference and corpus callosum growth was significant in the posterior of the callosum. The earlier MRIs were made at approximately the time that the peak of development in the callosum shifts from the anterior to the posterior, and so these results provide strong support for the proffered hypothesis.

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S3.5.3 MERCURY LEAD AND ZINC LEVELS IN BABY TEETH OF CHILDREN WITH AUTISM . .J. Romdalvik and J.B. Adams.Arizona State University, Tempe, AZ 85287-6006. V.M.S. Ramanujam and M. Lagatore. U. of Texas Medical Branch, Galveston, TX 88555-1110 Baby teeth begin to form during gestation, and continue to grow during the first several yaers of life. Previous studies have demonstrated that they can provide a measure of infantile exposure to toxic metals such as lead and mercury. In this study we compare the levels of mercury, lead and zinc in children with autism (n=15) versus controls (n=11). Participants: Arizona residents born 1988-1999, with a diagnosis of Autism Spectrum Disorders (ASD) or no diagnosis (unrelated controls). Methods: Cold-vapor Atomic Absorption Spectrophotometry (CV-AAS) on "digested" samples. Results: Mercury levels were 3x higher in the autism group(median of 0.14ppm vs 0.046 ppm, p=0.05). Lead levels were very similar (0.36 ppm vs 0.29 ppm) and zinc levels were very similar (93 ppm vs 96 ppm). Correlations with the severity of autism per the ATEC are pending. Discussion: These results are consistant with a previous study by A. Holmes et al. which found that children with autism had very low levels of mercury in their baby hair, suggesting impaired excretion. These results are also consistant with a study by J. Bradstreet et al., which found that children with autism excreted much higher levels of mercury than typical children when given DMSA, a chelating agent, which suggests a much higher body burden of mercury in children with autism. Funded by the Autism Research Institute (ARI) S3.5.4 SEROTONERGIC DYSFUNCTION AND BEHAVIORAL CHANGE IN THE EMBRYONAL THALIDOMIDE/VALPROIC ACID EXPOSED AUTISM MODEL RATS. N. Narita*, M. Tazoe and M. Narita. Inst. of Basic Med. Sci., U of Tsukuba. Tsukuba, Ibaraki, 305-8575, Japan. The difficulties in creating an animal model of autism lie in reproduction of heterogeneic social and communicative defects of human autism in animals. We have recently established an autism model rat by exposing embryonic day (E) 9 rat embryo to

either thalidomide (THAL) or valproic acid (VPA) (Pediatric Research, 52:576, 2002). The concept of our model rat was achieved from the etiology of human autism that these two teratogens are responsible for the occurrence of autism when they are exposed to early developing embryos. 500mg/kg THAL or 800mg/kg VPA was orally administered to pregnant female Wister rats, and on postnatal day 35-50, offspring were evaluated biochemically, morphologically, and behaviorally. We observed characteristic findings in them as follows; (1)Both THAL and VPA-exposed rats exhibited hyperserotonemia, and significant increase of serotonin concentration in the hippocampus. (2)Both THAL and VPA-exposed rats commonly showed morphological changes in the dorsal raphe nuclei, the origin of serotonergic neurons, suggesting a migration disorder of serotonergic cells in early developmental stage. (3)They showed impairment of the learning task achievement and increased non-exploratory movement in the radial maze test, some of which are relevant to human autism. These results indicate that two potentially autism inducing teratogens, THAL and VPA, may disrupt early serotonergic neuronal development in the embryo, and may cause behavioral changes observed in autism. S3.5.5 WIDESPREAD SIMILAR CORTICAL ASYMMETRIES IN AUTISM AND DEVELOPMENTAL LANGUAGE DISORDER ARE MOST PROMINENT IN HIGHER-ORDER ASSOCIATION AREAS. M. Herbert1,2,6, D. Ziegler1,2,

C. Deutsch4,5,7, L. O’Brien8, D. Kennedy1,2,3, P. Filipek9, A. Bakardjiev10, J. Hodgson11, M Takeoka12, N. Makris1,2 and V. Caviness Jr1,2 . 1Center for Morphometric Analysis, and Departments of 2Neurology and 3Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 4Department of Psychiatry, Harvard Medical School, Boston, MA; 5Psychobiology and Medical Genetics Programs, Eunice Kennedy Shriver Center, Waltham, Massachusetts; Departments of 6Neurology and 7Mailman Research Center, McLean Hospital, Belmont, MA; 8Department of Mathematics, Colby College, Waterville, ME; 9Department of Pediatrics, University of California, Irvine; 10Department of Infectious Diseases, Children’s

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Hospital Oakland; 11Augsburg College, Minneapolis, MN; 12Children’s Hospital, Boston, MA.

We analyzed volume asymmetries of a comprehensive set of brain areas derived from cortical parcellation. Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 developmental language disorder (DLD), 15 controls). Both autism and DLD showed an increase in aggregate total and rightward asymmetry within the cerebral cortex in both disorders. Regarding distribution of cortical asymmetries, we found significant differences among groups in higher order association cortex, but no differences in primary sensory and motor cortex. In addition, patterns of cortical asymmetry across the entire cerebral cortex differed from controls in both autism and DLD, but the two groups strongly resembled each other. The strong similarity in asymmetry alterations in the two disorders suggests a non-random disruption of neural systems. These similarly atypical asymmetries are widely distributed and occur in brains that also have large total brain and white matter volumes. This suggests that abnormal brain development in these disorders is pervasive; that volume, white matter and connectivity changes may contribute to altered asymmetries; and that distributed as well as focal anatomical abnormalities contribute to phenotype. These widespread abnormalities and prominent involvement of higher-order association areas may underlie a variety of secondary as well as primary features in these disorders, and could be related to the generalized or complex processing impairments that have been proposed to underlie the primary behavioral features. Acknowledgements: NS 20489, the Cure Autism Now Foundation, NS02126, NS27950, DA09467, Human Brain Project NS34189, Fairway Trust and the Giovanni Armenise-Harvard Foundation for Advanced Scientific Research.

Slide Session 3: Topic 6: The Development of

Young Sibling of Children with Autism

S3.6.1 FACE-TO-FACE INTERACTION OF INFANT SIBLINGS OF AUTISTIC CHILDREN: AN EXPLORATORY STUDY OF PATTERNS OF MUTUAL GAZE, SMILING AND VOCALIZATION. M. Gratier and A. Dijamco. Dept. of Psychology, 2279 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095 Face-to-face interactions between twelve four-to-six-month-old infant siblings of autistic children and their mothers were compared with those of twelve control mother-infant dyads. Video recordings of the mothers and infants communicating normally without using toys were made in both laboratory and home settings and one minute segments of interaction were analyzed for each dyad using a frame-by-frame coding system. The analyses yielded durations and frequencies of infant smiling, vocalizing and gazing at mother, mother smiling, vocalizing and gazing at infant, and forms of touch between mother and infant. Overall differences in smiling, gazing at mother and forms of touch were found between the siblings of autistic children and the control infants. Qualitative analyses also highlighted interactive features in one of the sibling infants which may constitute precursor signs of autism. S3.6.2 TEMPERAMENT IN INFANTS LATER DIAGNOSED WITH AUTISM . S.E. Bryson, L. Zwaigenbaum, J. Brian, W. Roberts, P. Szatmari and C. McDermott. Autism Research Unit, Hospital for Sick Children, Toronto, ON M5G 1X8. Background: Conceptual overlap exists between dimensions of “temperament” and behaviors considered to be part of the autistic phenotype (e.g., reactivity). However, there are few studies of temperament in children with autism spectrum disorders (ASDs), and none include data predating diagnosis. Our prospective study of high-risk infants (siblings of children with ASD) provides a unique

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opportunity to assess whether infants later diagnosed with autism show differences in early temperament compared to other children. Methods: Our sample includes 41 siblings and 20 low-risk controls (no family history of ASD) followed to at least 24 months of age. Parents completed the Infant Behavior Questionnaire (IBQ) at 6 and 12 months, and the Early Childhood Behavior Questionnaire (ECBQ) at 24 months. IBQ and ECBQ scores were compared between subgroups of siblings defined by ADOS classification at 24 months (autism, ASD, and non-ASD) and low-risk controls, using 1-way ANOVA and Tukey LSD post-hoc tests. Results: ADOS scores exceed threshold for autism in 4 of 41 siblings at 24 months, all of whom meet DSM-IV diagnostic criteria. Children with autism were rated at 6 months with lower activity level, at 12 months with more frequent and intense distress reactions, longer durations of orienting to particular objects and less smiling, and at 24 months with less attention shifting, less inhibitory control and less positive anticipation and affective responses, relative to other siblings and low-risk controls. Conclusions: Children with autism may show differences in temperament that are apparent beginning in the first year of life. Funded by NAAR and CIHR. S3.6.3 BEHAVIORAL MARKERS OF AUTISM IN HIGH-RISK 12-MONTH-OLDS. L. Zwaigenbaum, S.E. Bryson, J. Brian, W. Roberts, C. McDermott and P. Szatmari. Department of Pediatrics, McMaster University. Evel 4 PO Box 2000 Hamilton, Ontario, Canada, L8N 3Z5 Objective: To better inform early identification efforts, we have initiated a prospective study of high-risk infants, each with an older sibling with autism (siblings). Our main goal is to assess whether behavioral markers in the first year of life can identify infants most likely to receive a subsequent diagnosis of autism. Methods: The Autism Observation Scale for Infants (AOSI; Bryson et al., 2003) detects 18 behavioral risk markers hypothesized for autism. AOSI risk markers observed at 12 months in siblings (n=65) and low-risk controls (n=23) were assessed relative to diagnostic classification at 24 months of age as determined by the Autism Diagnostic

Observation Scale (ADOS). Results: 24-month ADOS scores exceed threshold for autism in 7 siblings (all subsequently received clinical diagnoses), and exceed threshold for “autism spectrum disorder” (ASD) in an additional 13 siblings (2 received clinical diagnoses). The number of AOSI risk markers observed at 12 months predicts ADOS classification at 24 months, based on 1-way ANOVA (F3,84=25.4; p<.001). The presence of 7 or more risk markers at 12 months prospectively identified 6 of 7 children diagnosed with autism at 24 months, compared to 2 of 58 non-autistic siblings, and 0 of 23 controls. Early risk markers predictive of autism include atypical eye contact, visual tracking, disengagement of visual attention, orienting to name, imitation, social smiling, reactivity, social interest, and sensory-oriented behaviour (all p<.003 to adjust for multiple comparisons). These findings will be illustrated using individual case examples. Conclusions: Signs of autism can be identified at 12 months in high-risk infants within a relatively brief but systematic clinical assessment. S3.6.4 THE DEVELOPMENT OF SIBLINGS OF CHILDREN WITH AUTISM: SOCIAL ENGAGEMENT AT 4 MONTHS. N. Yirmiya*, I. Gamliel, M. Sigman*, R. Feldman, T. Pilowsky and S. Baron-Cohen. Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem, ISRAEL 91905. We examined the social engagement of siblings of children with autism at age 4 months. Siblings of children with autism are at a greater risk to develop the "broad phenotype" of autism, i.e., related social, cognitive, and communicative impairments which are similar to those seen in autism although not strong enough to merit diagnoses of PDD spectrum disorders. Twenty-one dyads of mothers and siblings of children with autism, and 21dyads of mothers and siblings of typically developing children were examined during mother-child face-to-face interaction, and during the Still face paradigm. Synchrony of all types was found in 61.9% of the dyads in the autism sibling group, and in 66.7% of the dyads in the typical development sibling group. However, synchrony was stronger in the typically developing infants, M=.18, SD=.07, compared to the

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autism sibling group, M=.13, SD=.06, when the interaction was led by the infant; t (40)= 2.35, p=.03, two-tailed, d=.118, pointing to a closer affective match between mothers and infants in the typically developing siblings group. In the Still face procedure, siblings of children with autism displayed more neutral affect throughout the still face procedure, M=79.91%, SD =.18, than siblings of typically developing children, M=65.05%, SD=.24, t (34)=2.08, p=.045, two-tailed, d=.113. All other group and interaction effects were non-significant. These results are discussed in terms of the broad phenotype of autism. Nurit Yirmiya and Marian Sigman were supported by the United States-Israel Binational Science Foundation (BSF) grant number 97-00073 S3.6.5 RESPONSE TO JOINT ATTENTION AT 14 AND 24 MONTHS IN AUTISM SPECTRUM DISORDER: A LONGITUDINAL STUDY. M.T. Sullivan*, R. Landa, C. Taylor. Center for Autism & Related Disorders, KKI, Balt, MD 21211 Baby siblings of children with autism provide a unique opportunity to investigate the early stages of the disorder due to the increased genetic risk in siblings with a positive family history. Data were collected as part of a longitudinal study designed to prospectively identify early markers of autism in at-risk babies. Numerous studies have demonstrated that joint attention is deficient in young children with autism and is highly correlated with development of communication. The objective of this study was to identify prospective differences in the development of response to joint attention in children who are later diagnosed with ASD, in comparison to typically developing children, in the timeframe when joint attention is typically established. Responses to joint attention opportunities (Carpenter et al, 1998) were analyzed at 14 and 24 mo of age for toddlers later diagnosed with ASD (n=9) and toddlers showing no signs of developmental delay (n=25). T-tests revealed significant differences in response to joint attention for trials when the examiner shifted gaze to a target (p<.01) as well as shifted gaze combined with a point (p<.05). In both cases, children later diagnosed with autism were less likely to respond than the

typical children. These findings replicate previous demonstrations of a deficit in response to joint attention in young children with autism. Furthermore, this study suggests that these deficits are apparent as early as 14 mo of age. Variability in response to joint attention will be discussed in both populations as well as correlations with shared affect, gestures and verbal communication. Funded by NIMH, grant #1R01MH59630-01A3 Poster Session 3: Topic 1: Biological Markers In

Early Development. P3.1.1 A COMPARATIVE INVESTIGATION OF GROWTH PATTERNS DURING THE FIRST THREE YEARS OF LIFE OF INFANTS WITH HIGH-FUNCTIONING AUTISM AND ASPERGER'S DISORDER. C. Dissanayake 1, Q. Bui 2, D. Loesch 1 and R. Huggins 2. 1School of Psychological Science and 2School of Statistical Science, La Trobe University, Victoria 3086, AUSTRALIA, To date, there has been little systematic effort made to characterize the developmental anatomic phenotype of autism. While there is some evidence of an increased head circumference in early development, few other physical characteristics of individuals with autism have been studied. The head circumference and length/height of infants who later received a diagnosis of high functioning autism (n = 24) and Asperger’s Disorder (n = 12) was extracted from infant health records over the first three years of life and compared to the infant data of a control group of typically developing children (n = 24). Using linear mixed-effects models, the average growth rate for both head circumference and length of the infants with high functioning autism and Asperger’s Disorder was significantly higher than the average growth rate identified for the typically developing infants during the first three years. No differences were found in the average growth rate for either head circumference or length between the two clinical groups. These results indicate that growth dysregulation in autism is not specific to the brain but involves other body systems as well. The results from these physical data concur with much behavioural data to support the notion that high

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functioning autism and Asperger’s disorder are not distinct diagnostic entities but rather belong on the same autism spectrum. P3.1.2 IMPACT OF ENVIRONMENTAL FACTORS ON BRAIN DEVELOPMENT AND BEHAVIOR IN MALES AND FEMALES. E.M. Sajdel-Sulkowska 1,2,* K. Nguon 2, B. Ladd 2, M.G. Baxter 3. 1Harvard Med. Sch., 2BWH, 3Harvard U., Boston, MA 02115 Despite a well-recognized gender difference in autism, with a male-to-female ratio of 4:1, the etiology of male predisposition remains unclear. So far neither the genome scans on the X chromosome nor the Y-haplotype distribution have provided an adequate explanation for this gender difference. In search of the possible clues, we have looked for differences in male vs. female response to neurotoxins during brain development by comparing cerebellar structure and behavior in rat neonates exposed to the PCB mixture Aroclor 1254 (10.0 mg/kg/day) from gestational day 11 until postnatal day (P) 21 to controls. A1254 exposure affected righting response; negative geotaxis; startle response; and performance on a rotorod, with PCB-treated male pups more severely affected than female. Behavioral changes of PCB-exposed pups were associated with a decrease in cerebellar mass and abnormalities in laminar organization. Western analysis suggested gender-specific changes in glial and neuronal cerebellar proteins. These results suggest that PCB exposure affects brain development and behavior, with greater effects observed in male pups. The nature of PCB impact resembles some of the aspects of the autistic syndrome, where behavioral and cerebellar abnormalities are more frequent in males. Thus PCB-exposed rat neonates may provide a model for understanding the different degrees of susceptibility to environmental toxins in males and females. This knowledge is relevant to understanding the risks of developmental exposure in humans to environmental insults, and their contribution to the pathogenesis of neurodevelopmental disorders such as autism. Supported by NIEHS R01-ES111946-02 (ESS).

P3.1.3 BEHAVIORAL SENSITIVITY TO METHYLMERCURY FOLLOWING PRENATAL OR EARLY POSTNATAL EXPOSURE. A.K. Halladay 1,3, G.C. Wagner 2,3 and K.R. Reuhl 1,3, 1Departments of Pharmacology and Toxicology, and 2Psychology, 3Rutgers University, New Brunswick, NJ and the Center for Neurotoxicology and Exposure Assessment While the etiology of autism and pervasive developmental disorders is poorly understood, exposure to environmental neurotoxicants during critical periods of neural and behavioral development may contribute to the heterogeneity of symptoms seen in this disease. The spectrum of delays, regressions and intrusions in behavior may be the result of multiple toxicant exposure at different periods in neurodevelopment. To examine the effects of early postnatal and/or gestational exposure to the neurotoxicant methylmercury (MeHg), animals were treated with MeHg or PBS on gestational days 10-14, or treated with MeHg or PBS on alternate postnatal days (PND) 3-13. Later toxicant or vehicle challenge was administered on PND 15. While animals exposed prenatally with MeHg showed a developmental delay of odor preference, surface righting, and mid-air righting, there was no effect of later MeHg challenge. Impairments in spatial navigation produced by MeHg on PND 15 were exacerbated if animals were also exposed to MeHg during gestation. In addition, those treated with 8 mg/kg MeHg on PND 3-13 showed a delay in the development in the negative geotactic response followed by a regression in this behavior when challenged with MeHg on PND 15, an effect not observed when lower doses of MeHg were administered. This suggests that differential behavioral impairments following MeHg may be the result of neural insult at varying periods of development, and that functional consequences can be altered following earlier exposure to this neurotoxicant. (Supported by NIH ES11256) P3.1.4 MOLECULAR AND CELLULAR BASIS OF SEROTONERGIC DYSFUNCTION IN THE EMBRYONAL THALIDOMIDE/VALPROIC ACID EXPOSED AUTISM MODEL RATS . M. Narita*, M.

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Tazoe, and N. Narita. Inst. of Basic Med. Sci., U of Tsukuba. Tsukuba, Ibaraki, 305-8575, Japan. Embryonic exposure to thalidomide (THAL) or valproic acid (VPA) before neural tube closure has been demonstrated as a useful model for human autism in rats. Abnormalities of the serotonergic system which are often observed in human autism have been shown in these rats. In this study, we examined whether early serotonergic neuronal development and mRNA expression of related genes are perturbed by THA/VPA. When pregnant rats were exposed to THA or VPA on embryonic day 9, a dramatic shift of the distribution of serotonergic neurons in the dorsal raphe nucleus was observed on postnatal day 50. This alteration is thought to reflect abnormality of serotonergic neuronal differentiation and migration. In vitro studies revealed that VPA retards the maturation of serotonergic neuron from ES cell-derived neuronal progenitors, whereas exogenously added Sonic hedgehog, a morphogen that has been implicated in serotonergic cell fate, partially prevented this retardation. Moreover, by analyzing mRNA expressions in the embryos and the cells exposed to THAL or VPA, we found alterations of genetic expression of Sonic hedgehog signal pathway, ETS domain transcription factor, Pet-1, and serotonin transporter. These results indicate that disruption of early serotonergic neuronal development induced by genetic transcriptional alteration by the teratogens might be responsible for the etiology of autism. P3.1.5 GABRB3 GENE EXPRESSION IN DEVELOPING MOUSE BRAIN . T.M. DeLorey*, T. Wei, E. Hashemi and O. Mateeva. Molecular Research Institute, Mountain View, CA 94043 Objective: A growing body of evidence has implicated chromosomal region 15q11-13 as contributing to Autism. This region contains the GABRB3 gene, which remains a good candidate gene. For this reason we were interested in further investigating the role of this gene in development. As an initial starting point we assessed the expression levels in mouse brain of the gabrb3 gene containing either exon 1 or the alternative exon 1a. Methods: Upon identifying the mouse equivalent of

the DNA sequence of the exon 1a of the GABRB3, we employed real-time PCR to assess the expression levels in mouse brain of the gabrb3 gene containing exon 1-2, exon 1a-2, and exon 5-6 at 10 separate development stages, including embryonic days 12, 14, 16, 18, Postnatal days 1, 4, 7, 14, 21, and 60. Results: PCR products from exon 1-2, exon 1a-2 and exon 6-7 of the gabrb3 gene were found to be expressed at all developmental time points examined. However, the relative amount of exon 1-2 vs. exon 1a-2 varied throughout the developmental time points studied. Conclusion: These results support the likelihood that both exon 1 and exon 1a of the gabrb3 gene contribute to the development of the Central Nervous System in mammal. These findings serve as a baseline for future studies aimed at elucidating the developmental role of each of these alternative exons and the consequences arising from defective expression of either exon. Research funded by NIMH RO1 MH065393-01. Poster Session 3: Topic 2: Joint Attention, Play

and Social Development

P3.2.1 DEVELOPMENT OF SOCIAL BEHAVIOR OF CHILDREN WITH AUTISM: NATURALISTIC OBSERVATIONS IN THE CLASSROOM ENVIRONMENT. A. Dijamco, L. Travis and M. Sigman*. University of California, Los Angeles; Los Angeles, CA 90024. This longitudinal study examines the social performance of 36 young children with autism in the classroom environment. Naturalistic observations and laboratory assessments were conducted over a four-year time period. Children entered the study between the ages of 2 and 5 years. The project investigates the relations among language, joint attention, early social behavior, and classroom structure as correlates and predictors of social outcome. Social performance was measured by frequency of parallel behavior, a learning-related social skill, along with more advanced levels of play. It was hypothesized that each of the aforementioned areas would be positively associated with both concurrent social performance and growth over time

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in social behavior. The longitudinal measurements were analyzed using a random intercept and slope (RAIS) model. By estimating slopes to index rate of change over time, this method enabled comparisons among individuals of various ages and levels of abilities. Preliminary analyses produced mixed findings. Children who were initially higher in language age, mental age, initiating joint attention, and responding to joint attention displayed a greater increase in overall parallel behavior over time. Positive correlations were especially significant during structured time. However, contrary to previous findings, the higher these children performed initially, the less engaged the children seemed to be later on during free play. This unanticipated finding produced consistently negative correlations across different domains. Follow-up analyses will be conducted once data collection at Time 4 has been completed. P3.2.2 VALIDITY INVESTIGATION OF TWO MEASURES OF PERSEVERATIVE OBJECT USE IN YOUNG CHILDREN WITH AUTISM . C. Taylor*, and P. Yoder. Vanderbilt University. The purpose of this study was to investigate the construct validity of several different metrics for quantifying perseverative object use. Perseverative object use may restrict generalization of newly learned play and communication skills and is one facet of the construct "restricted interests" in very young children with autism. We used Cronbach & Meehl (1955) nomological network logic to test the construct validity of the alternative metrics for this construct. A concurrent and longitudinal correlational design was used. The children in this study were diagnosed with autism and at time 1 had a mean chronological age of 2.8 years (SD= 0.73). The data for perseverative object use variables were measured during time 1 administration of the Developmental Play Assessment (Lifter, 1988). The results support the construct validity of (a) the number of toys that the child touched (significantly positively correlated with RJA on the ESCS at time 1 and turn taking at time1) and (b) the ratio of the number of toys upon which the child performed more than one differentiated play action/total number of toys touched

(significantly positively correlated with RJA on the ESCS at time 1 and time 2 even after controlling for Time 1 cognitive play level). Research is funded by NIDCD R01DC03481. Second author is also supported by a NICHD grant to the Kennedy Center (HD15052) P3.2.3 THE RELATIONSHIP BETWEEN EXPRESSIVE/RECEPTIVE LANGUAGE ABILITIES AND RESPONDING TO THE JOINT ATTENITON BIDS OF OTHERS AND INITIATING JOINT ATTENTION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. D. Murray, N. Creaghead, P. Manning-Courtney, J. Bean, P. Shear and J. Prendeville, University of Cincinnati and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. 45229. The purpose of this study was to investigate the relationship between response to joint attention and initiation of joint attention and selected individual components of language in twenty children diagnosed with autism spectrum disorder between the ages of 3-5 years. Results: Results from analyses revealed a significant correlation between response to joint attention and mean length of utterance, MLU, (r= .554, p=.0112) and response to joint attention and the receptive raw score of the Mullen Scales, MSELR, (r= .554, p=.0113). The relationship between response to joint attention and type token ratio, TTR approached significance (r=.428, p=.0596). The results revealed no significant relationship between initiation of joint attention and any of the selected components of language, (MLU r= .278, p=.2348, TTR r= .2915, p=.2123). No significant correlation existed between response to joint attention and initiation of joint attention (r=.318, p=.1714). A McNemar’s test indicated that the skill of a clinically acceptable response to the joint attention bids of others is not associated with the ability to initiate joint attention at a clinically acceptable level. Conclusion: The results suggest a relationship between the ability to respond to the joint attention bids of others, and receptive and expressive language abilities.

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P3.2.4 CORRELATES AND PREDICTORS OF PEER INTERACTION IN AUTISTIC SPECTRUM DISORDER. H. Schmidt*, C. Lord and S. Risi. University of Michigan Autism and Communication Disorder Center, University of Michigan, Ann Arbor, MI 48109. A central aspect of autistic spectrum disorder is a deficit in peer interaction, and identification of early predictors of impaired social functioning could aid in choosing appropriate interventions and treatments. In addition, researchers such as Wing and Gould (1979), have attempted to identify subgroups of autistic spectrum disorder in order to aid in treatment and school decisions, as well as predict which children will have better outcomes. In the present study, eighty-two children with autistic spectrum disorder, divided into four subgroups following the Wing and Gould (1979) descriptions of types of social deficit, and a control group of thirteen children with developmental delay were assessed at age two and age nine. Early and current IQ scores and scores on the Autism Diagnostic Interview - Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS), and the Vineland Adaptive Behavior Scales were used to identify correlates and predictors of Wing and Gould groupings, as measured by the Interact and Disconnect items of the Penn Interactive Peer Play Scales (PIPPS). Current IQ showed a strong relationship to level of peer interaction, and current class placement was also related. Early level of joint attention, as measured by items on the ADOS, was the strongest predictor of later peer interaction. This study was a thesis required for the degree of Bachelors with Honors at the University of Michigan. P3.2.5 IMMEDIATE AND DEFERRED IMITATION OF CHILDREN WITH AUTISM. C.C. Wu and C.H. Chiang. Department of Psychology, National Chung Cheng University. 160, San-Hsing, Ming-Hsung, Chia-Yi 621, Taiwan R.O.C. The purpose of this study was to compare with the difference of the immediate and deferred imitation abilities among children with autism (mean CA = 40.73 months, mean MA = 24.13 months), developmental delays and normals. Modified from

Rogers, et al. (2003) and Stone, et al. (1997), we used four tasks for evaluating the immediate imitation abilities: objects employ meaningful action, objects employ nonmeaningful action, manual movement and oral-facial movement. For evaluating deferred imitation ability, we used three materials from Meltzoff(1988) and delayed 10 minutes. During the modeling phase, the experimenter would say” (name), look over here” or “(name), see what I have”. During the response phase, the experimenter would say” it’s your turn”. The experimenter never said any words relating to task at hand. If the item involved an object, the experimenter gave children 20 seconds to explore the object. The result revealed that, unlike other previous similar studies, children with autism have similar abilities of overall imitation, immediate imitation, and deferred imitation abilities as the children have in the other both groups. The finding may be due to our subjects who have higher mental age and were trained in the day hospital program. We does not imply that the children with autism are not impaired in imitation, but high functioning autistic children could have simple imitation after an appropriate training. Acknowledgements: This study was supported by NSC Grant 91-2413-H-194-013 in Taiwan for the second presenter. P3.2.6 PARENTAL REPORTS OF THE EMPATHIC BEHAVIOUR OF YOUNG CHILDREN WITH AUTISM, DOWN SYNDROME, AND TYPICAL DEVELOPMENT . K. Hudry and V. Slaughter. Early Cognitive Development Unit, School of Psychology, University of Queensland, Brisbane, Australia, 4072. Empathy in young children with Autistic Spectrum Disorder has been evaluated using variations of Sigman et al.’s (1992) paradigm. Participant children are presented with in vivo scenarios designed to elicit empathy (e.g., an adult hurting her finger whilst playing), and their response behaviour is observed. Such studies tend to find that children with autism respond less empathically than do other groups of children (with or without intellectual impairment, and matched on verbal mental age). However, parents of children with autism are often able to recall instances in which

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their child behaved quite empathically, suggesting that children with autism are not incapable of empathy. The Day-to-Day Child Empathy Questionnaire, designed to obtain parental descriptions of children’s spontaneous empathic behaviour, was administered to parents of children with autism, Down Syndrome, and two matched groups of typically developing children. Analyses (primarily qualitative) were conducted on parent responses to an open-ended probe eliciting descriptions of day-to-day situations in which their child behaved empathically, as well as descriptions of their child’s typical behaviour during those situations typically sampled in experimental empathy studies. Analyses to date reveal a difference in the empathic behaviour of children with autism compared to controls, such that the children with autism tend to restrict their empathic responses toward known adults or children. This has important methodological implications for experimental tests of empathy, which will be discussed. P3.2.7 THE CONTRIBUTIONS OF COGNITIVE ABILITY, SOCIAL RECIPROCITY, AND MOTOR SKILLS TO IMITATION PERFORMANCE IN CHILDREN WITH ASD . L. Turner, W. Stone* and T. Ulman. Vanderbilt University, Nashville, TN, 37232. The purpose of the present study was to examine the differential contributions of cognitive ability, social reciprocity, and fine motor skills to performance on different types of motor imitation tasks. Forty children with ASD between the ages of 24 and 46 months participated in cognitive, diagnostic, and imitation assessments. Cognitive ability and fine motor skill level were measured with the Mullen Scales of Early Learning. Social reciprocity was measured with the ADOS-G reciprocal social interaction scale. Imitation was assessed with three measures: an unstructured naturalistic imitation task (NIM), a structured object imitation task yielding a sensory reward (SIM), and a structured task involving imitation of body movements and actions on objects (MIS). Hierarchical linear regression was conducted for each imitation measure to determine the relative contributions of cognitive ability, fine motor skills, and social reciprocity to imitation performance. For

the NIM, fine motor skills and social reciprocity contributed to imitation performance, but only social reciprocity made a significant unique contribution. For the SIM, cognitive ability and fine motor skills contributed to imitation performance, but only fine motor skills made a significant unique contribution. For the MIS, all three predictors contributed to imitation performance, but only fine motor skills and social reciprocity made significant unique contributions. These findings indicate the importance of all three developmental areas to imitation ability and suggest that different skill sets may be necessary for different types of imitation tasks. NIH/NICHD R21 HD42437 P3.2.8 THE IMPORTANCE OF CONTEXT IN SOCIAL RESPONSIVITY AND INITIATION . C. Shulman and E. Kanfi. School of Social Work, The Hebrew University of Jerusalem. Social interaction in young autistic children has been studied extensively, comparing assorted variables. The present research incorporates findings from separate studies into a parsimonious methodology, enabling comparisons among variables. Initiations and responses were studied and compared in three contexts, differing in structure and familiarity. Forty-two children participated in the research in three matched groups (autism, mental retardation and typical development). The clinical groups were matched for mental and chronological ages and typical children matched for mental age. Between-group comparisons revealed that autistic children show less social responses and initiations than the other children. Specifically, in unstructured contexts, autistic children showed fewer initiations than the others, and, surprisingly, showed fewer responses than the children with mental retardation. In structured contexts, autistic children exhibited less initiation and responsivity than the others. Iin the unfamiliar structured context, while children with autism initiated less, no differences emerged among the groups in their responsivity. Within-group analyses revealed that children with autism respond more in structured contexts than in unstructured contexts. Children with

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autism initiated more frequently to adults than to peers. These findings confirm the importance of structure in social interaction and compare initiations/responses and familiarity/structure. Such comparisons advance our understanding of the specificity of the social impairments in young autistic children and can provide effective intervention strategies for young autistic children. P3.2.9 THE PATTERNS OF SOCIAL GAZING AND THEIR INTENTIONAL COMMUNICATION IN YOUNG CHILDREN WITH AUTISM . C.H. Chiang 1 and W.T. Soong 2. 1Department of Psychology, National Chung Cheng University. 160, San-Hsing, Ming-Hsung, Chia-Yi 621, Taiwan R.O.C.; 2Department of Psychiatry, Institutes of Psychology and Epidemiology. National Taiwan University. 7 Chung-San South Rd., Taipei 100, Taiwan R. O. C. The study explored the patterns of spontaneous social gazing and their intentional communicative in young children with autism. The subjects were 22 young autistic children, aged below 42 months (mean CA = 32.8 months, mean MA = 22.1 months), 23 MA matched children with developmental delay and 24 18-20-month-old normal infants (we also added 23 13-15-month-old younger normal infants). Based on Chiang & Soong (2001)�s task for measuring the intentional communication, object-object gazing, object-person gazing, and low and high intentional communication were counted for the four groups. The results found that young children with autism showed highest frequency on object-object gazing, but lowest frequency on object-person gazing. We also demonstrated that young children with autism could interact with others by alternating provided that there is high motivation, but they seemed to have limitation to develop high-level or flexible communicative means to negotiate with others. The abnormality in social gazing and its intentional communicative ability was shown in early development in autism. Acknowledgements: This study was supported by NSC Grant 89-2413-H-194-060 and 90-2413-H-194-028 in Taiwan for the first presenter.

P3.2.10 A LONGITUDINAL ANALYSIS OF PRETEND PLAY IN AUTISM . M.D. Rutherford, S.J. Rogers and S. Hepburn. University of Colorado, Health Sciences Center., Denver, CO 80262. Typically developing children spend a great deal of time engaged in pretend play, whereas children with autism are less likely to spontaneously generate pretend play. The study described here uses a longitudinal design to test for deficits in pretend play development in a group of children with autism, compared to typically developing and developmentally delayed mental age matched participants. We test the hypothesis that developmental change in pretend play performance can be predicted by earlier measures of either executive function, joint attention, imitation, or by general developmental measures. Participants at the time of second testing were 28 children with autism disorder (AD) (mean C.A. 57.6 mos), 18 children with other developmental disorders (mean C.A. 59.0 mos), and 27 typically developing children (mean C.A. 30.1 mos). Measures of the development of intersubjectivity, of executive function, of imitation and of general development at initial testing (time 1) are used to predict development in pretend play performance between time 1 and follow-up testing. The Fewell Play Scale was used to assess pretend play levels. Children with autism were significantly delayed on pretend play scores at both time 1 and time 2. Joint attention at time 1 strongly and uniquely predicted pretend play development in this age group. Children with autism were profoundly delayed given competence (prompted) measures as well as performance (spontaneous) measures. The AD groups master the items of the play scale in a non-cononical order, suggesting deviance, not just delay, in play development. P3.2.11 SOCIAL ORIENTING AS A CONSTRUCT UNDERLYING JOINT ATTENTION AND OTHER SKILL DEFICITS IN A SAMPLE OF PRESCHOOL CHILDREN WITH AUTISM . S.B. Reavis, MA and G.B. Mesibov, Ph.D.* University of North Carolina at Chapel Hill, Chapel Hill, NC 27502. This study examines the relationship between joint attention and multiple child characteristics

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believed to have a social basis, using a sample of preschoolers with autism. The project seeks to understand complex relationships between joint attention and child characteristics of imitation of body movements, language, gender, and severity of autism, which may be associated with social abilities in young children with autism. Analyses were conducted using correlations, t tests, and Poisson regression models predicting joint attention from multiple developmental variables. Findings based on a sample of 18 preschool children with autism indicated that imitation of body movements, level of autism severity, and gender best predicted variance in joint attention. Separate analyses for gender were conducted, leading to the findings that girls in this sample more strongly predicted joint attention than boys. The conclusion discusses potential reasons for these gender differences seen, limitations of this study, and directions for future research. P3.2.12 JOINT ATTENTION BEHAVIORS IN CHILDREN WITH AUTISM: STABILITY AND CHANGE DURING THE PRESCHOOL YEARS . M. Siller and M. Sigman*. Department of Psychology, University of California at Los Angeles, Los Angeles, CA 90024. The capacity to coordinate attention with others vis-à-vis objects or events (referred to as joint attention) is considered critical for the social and language development of young children. Moreover, when compared to matched controls, children with autism show a characteristic deficit in joint attention behaviors. This study aims to evaluate the stability and change of specific joint attention behaviors in a sample of young children with autism. Thirty-three children with autism (CA = 47 months) were recruited and followed over a period of 3 years. Over the course in the study children’s joint attention skills were evaluate annually using the Early Social Communication Scale (ESCS). The ESCS provides measurements of four specific joint attention behaviors: a) looking up while manipulating a toy (JA-Looks), b) alternating gaze between an interesting event and another person’s face (JA-Alternates), c) pointing to or showing objects to other people, and d) following others’ pointing gestures. The results showed that the frequency of three out

of four joint attention behaviors increased significantly over time. The only behavior which frequency did not increase was “JA-Alternates”. In addition, children’s improvements in “JA-Looks” were independent from children’s growth in language skills. These findings suggest that measures of joint attention may be a sensitive way to evaluate developmental growth and intervention outcomes in young children with autism. Supported by the M.I.N.D. Institute Research Program and Program Project Grant HD-DCD35470 P3.2.13 STRUCTURED VS. NATURALISTIC OBJECT IMITATION IN YOUNG CHILDREN WITH ASD. W. Stone*, T. Ulman, A. Swanson, C. McMahon and L. Turner. Vanderbilt University, Nashville, TN, 37232. Imitation skills are often taught in structured settings, though an important goal for children with ASD is the spontaneous imitation of peers during play activities. The relation between children’s performance on structured and naturalistic imitation tasks has not yet been assessed, but would seem to have important implications for designing imitation interventions. The present study had two aims: 1) to compare performance on structured and naturalistic imitation tasks in a group of young children with ASD; and 2) to examine developmental correlates of the two types of tasks. Forty children with ASD between 24 and 46 months of age participated in this study. The naturalistic measure consisted of a floor play activity in which an examiner imitated the child’s actions with toys and then demonstrated different actions with the same toys. The two structured measures took place at a table where an examiner modeled an action with an object and then presented it to the child; one measure employed social reinforcement and the other employed sensory reinforcement. Results revealed that children with ASD showed differential performance on the two types of measures, with stronger performance evidenced on structured tasks relative to the naturalistic task. In addition, the different types of measures showed different patterns of correlations with putative precursor skills. Performance on structured tasks was related to measures of visual attention and motor skills, while

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performance on the naturalistic task was related to a measure of social interest. These results are discussed in terms of their implications for increasing the effectiveness of imitation interventions. NIH/NICHD R21 HD42437 P3.2.14 SLIGHTLY DIFFERENT MECHANISMS OF IMITATION BETWEEN CHILDREN WITH AND WITHOUT AUTISM. Y. Kunihira, A. Senju, T. Hasegawa and Y. Tojo. Dept. of Cognitive and Behavioral Science, Univ. of Tokyo. Tokyo, 153-8902, Japan. We investigated whether the mirror image- or anatomical imitations and the positional relationship affect the performance of imitation in children with and without autism. Fourteen children with autism (mean age 11.9) and 18 typically developing children (mean age 11.8) participated in two kinds of imitation tasks: imitating the model’s simple hand action such as moving one hand to the ear (Hand and Ear Test; Head, 1920) or holding both hands out in front with the palms presenting backward or forward (Palm Test; referring to Ohta (1987)). There were two within-subject factors: positional relationship between the model and the child (face to face or side by side) and task instructions (for mirror-image or anatomical imitation). As a result of Hand and Ear Test, when sitting face to face, both children with and without autism made more mistakes in anatomical (i.e. crossed) than mirror-image imitation. But when sitting side by side, only typically developing children made more mistakes in mirror-image (i.e. axisymmetrical) than anatomical imitation, while there was no such tendency in children with autism. As for Palm Test, children with autism made 180° rotation mistakes (i.e. confusing the palms’ direction of backward or forward) more frequently than typically developing children in both face to face and side by side position, which might suggest that children with autism made such rotation mistakes not because they were face to face with the model. These results indicated that children with autism may use somewhat different mechanisms in imitation from those of typically developing children.

P3.2.15 PERCEPTUAL CAUSALITY IN YOUNG CHILDREN WITH AUTISM . A. Schlottmann and E.D. Ray. Dept of Psych, Univ College London. In recent work, 3-year-olds already link Michotte’s launch event to physical and Kanizsa & Vicario’s reaction event to social/psychological causality. We considered perceptual causality in 24 children with Autism (average age 8.4), 19 children with general Learning Difficulties (8.8) and 25 normal children (4.7), matched for mental age. Children saw two computer-animated squares: Red moved towards Green, then stopped and Green moved away. The squares made contact or not, moved simultaneously, contiguously or with delay, and moved rigidly or non-rigidly. Children chose which target picture (man kicking ball for physical causality, man chasing man for psychological causality, man walking alone for non-causal motion) best fit each event. Children with Autism differed statistically from normal children and children with Learning Difficulties, but the latter groups did not differ: Children with Autism performed well on no-contact events, appropriately giving more psychological attributions to reaction than delayed control events. However, responses for contact events were at chance level, while normal children attributed physical causality far more often to launch than control events. In control tasks, children with Autism were slightly better at physical reasoning, but surprisingly not significantly worse at Theory-of-Mind than the other groups. Difficulties with launch events agree with the central coherence account of Autism, but spared performance for reaction events does not. However, better than usual Theory-of-Mind ability in this sample could contribute to good performance on reaction events. Perceptual causality in children with Autism and low Theory-of-Mind skills remains to be tested. (supported by Leverhulme Trust project grant no F/07134/1). P3.2.16 LONGITUDINAL RELATIONS BETWEEN PLAY AND GESTURE BEHAVIORS IN INFANTS WITH AUTISM. L.R. Watson, G.T. Baranek, E.R. Crais, E. Collins, J. Dykstra and V. Poston. Univ. N. Carolina, Chapel Hill, NC 27599.

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The longitudinal relationships between the frequency and quality of different subclinical behaviors in infants with autism may reveal mechanisms for the development of the disorder. This paper presents longitudinal data on gesture and play behaviors in infants with autism spectrum disorders (ASD), developmental delay, and typical development (TD). Gesture and play behaviors were explored via retrospective analyses of home videos of young infants at 9-12 months and 15-18 months of age. Data coding is ongoing. Preliminary analyses of 8 infants with ASD and 5 infants with TD were conducted using cross-lag panel correlations (Spearman rho) to examine the relationships between Time 1 and Time 2 play and gesture behaviors. For TD infants, the highest level of play at Time 1 predicted play at Time 2 (rho=.79) and was moderately related to total gesture use at Time 2 (.61). Total gesture use at Time 1 predicted gestures at Time 2 (.92), but did not predict highest play level at Time 2 (-.33). For infants with ASD, there was a moderate degree of relation between highest play level at Time 1 and total gesture use at Time 2 (.69), but all other correlations fell below the .50 level. Thus, our preliminary analyses suggest similar relations between highest play level at Time 1 and gesture use at Time 2 for the ASD and TD groups; however, infants with ASD do not show the same level of predictability as TD infants for within-class play and gesture behaviors from Time 1 to Time 2. Support: Pilot research grant from Cure Autism Now; Medical Faculty Award and University Research Council Grant from the University of North Carolina at Chapel Hill; and NICHD (1R01HD042168) Poster Session 3: Topic 3: Microbiology and immunology of Autism Spectrum Disorder P3.3.1 FAMILIAL AUTOIMMUNITY AS A RISK FACTOR FOR REGRESSION IN CHILDREN WITH AUTISM SPECTRUM DISORDER. C.A. Molloy, A.L. Morrow, J. Meinzen-Derr and C. Lord. Collaborative Programs of Excellence in Autism and Cincinnati Children’s Hospital Medical Center Univ of Cincinnati Coll of Med., Cincinnati, OH 45229.

This study was undertaken to compare the family history of autoimmune disorders in children who have Autism Spectrum Disorder (ASD) with and without a history of regression. A multicenter study of children with ASD was conducted through the NICHD sponsored Collaborative Programs of Excellence in Autism (CPEA). Diagnosis of ASD was confirmed by the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnostic Observation Schedule Generic (ADOS) administered at the time children were enrolled in CPEA studies. Regression status was determined from the results of the initial ADI-R and follow-up telephone interview. Family history of autoimmune disorders was obtained from telephone interview. Results: Among the 308 study children with ASD, 153 (50%) had a history of regression. Regression was significantly associated with a family history of autoimmune disorders (adjusted odds ratio = 1.83; 95% CI:1.14, 2.93). The relative risk for regression increased if the family history included autoimmune thyroid disease (adjusted odds ratio = 2.00; 95% CI: 1.21, 3.30), and was greatest if autoimmune thyroid disease was present in a maternal relative (adjusted odds ratio = 2.48; 95% CI: 1.44, 4.29). Conclusion: This national study found familial autoimmune disease, especially autoimmune thyroid disease, to be a significant risk factor for regression in children with ASD. P3.3.2 IMMUNE PHENOTYPES IN AUTISM SPECTRUM DISORDER. J. Meinzen-Derr, C.A. Molloy, A.L. Morrow and M. Wills-Karp. Cincinnati Children’s Hospital Medical Center. Cincinnati, Ohio, 45229. We are conducting a case-control study to address the question of peripheral blood cytokine levels as measures of immune response patterns in children with ASD. From 6/1/2003 to 5/31/2005, we expect to enroll 40 cases and 40 matched controls (neurotypical development). We are reporting preliminary results of the cytokine measurements. Results: The medians of TH2 cytokines are consistently higher in cases than controls, but these differences are not significant. The ratio of IL-4 to IFN-g is a measure of the relative amount of TH2 to TH1 cytokines within each subject. The median IL-4/

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IFN-g in cases = 0.015 (n = 12). In controls the median ratio = 0.019 (n = 10). Differences were more notable among cases when comparison was made by history of regression. Within the case group, 5 children (42%) had a history of regression. Among these 5 children, 4 had an IL-4/ IFN-g ratio >0.03. In comparison, none of the children with no history of regression (n=7) had an IL-4/ IFN-g ratio > 0.03 (Fisher�s Exact p=0.01). Although no significant differences were seen between cases and controls with respect to TH1 and TH2, these results suggest an increase in TH2 relative to TH1 cytokines in children with the regressive phenotype. Conclusion: Characterization of our first cases in this study suggests that the regressive phenotype of ASD is associated with a relative elevation of TH2 cytokines, supporting the hypothesis that immune dysfunction or dysregulation is related to this regressive phenotype. In support by Cure Autism Now Foundation Pilot Project Grant Poster Session 3: Topic 4: Perception, Attention,

Learning and Memory P3.4.1 THE EXAMINATION AND TRAINING OF MEMORY STRATEGIES IN CHILDREN WITH AUTISM. J. Bebko and T. Rhee. Department of Psychology, York University, Toronto, Ontario, Canada M3J 1P3 This was an extension of our previous work into the use and training of memory strategies in children with autism (Bebko et al, 2001). The purposes of the current study were to: a) investigate spontaneous strategy use in children with autism, b) carefully train the participants to use a memory strategy (cumulative rehearsal) and metacognitive strategy when faced with a recall situation, c) examine maintenance and use of the newly learned strategy at a later date to enhance their recall ability, and d) investigate whether they would generalize what they had learned to novel material. Two groups of children were tested: a sample with autism functioning in the moderate to high range, and a control sample consisting of children with developmental disabilities and typically

developing children, matched to the functional levels and chronological ages of the sample with autism. Strategy training sessions entailed direct one-on-one teaching to have the participant rehearse repeatedly to him/herself in a cumulative fashion. Number of training sessions ranged from one to four, depending on the child’s speed of learning. A final follow-up session was conducted 2-3 weeks after the last training session to see whether the participant was able to maintain and generalize the newly learned strategy. Results to date indicate that strategy and metacognitive training was immediately effective in improving memory skills, with all children acquiring the strategy. Long lasting effects are still being examined. Implications for the training of memory strategies to children with autism will be discussed. P3.4.2 IMPAIRED AUDITORY PROCESSING IN YOUNG CHILDREN WITH AUTISM: AN ERP STUDY. M.D. Bomba, W.J. Logan, W. Roberts and E.W. Pang*. Division of Neurology, Hospital for Sick Children, Toronto, Canada, M5G 1X8. Autism is a developmental disorder characterized by impairments in social interaction and communication, and the presence of stereotyped behaviors. While it is known that individuals with autism have difficulty with cortical auditory processing, the exact impairment remains unknown. To address this issue, the cortical auditory event-related potential (ERP) known as the mismatch negativity (MMN) was examined. The MMN is a pre-perceptual physiological measure of the accuracy of sound representation and discrimination in the brain. In this study, the MMN was recorded in young children (3-5 yrs) with autism (N=7) and age/sex-matched controls (N=7) while they listened to tones (1 vs. 1.1 kHz) and a pair of speech sounds (/ba/ vs. /ga/) presented in an oddball paradigm. For the tone condition, the MMN was absent in the autism group. In the speech sound condition, the MMN was present in the autism group, but it was significantly smaller (p<0.01) and later (p<0.01) than in the control children. The absence of an MMN to the tones suggests that children with autism have great difficulty making fine acoustic discriminations. The smaller and later MMN

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to speech sounds suggests that children with autism have greater difficulty (and require more time) making linguistic discriminations. These findings support the generally held assumption that children with autism have auditory processing deficits since the MMN is abnormal regardless of the type of stimuli presented. However, these findings suggest that these deficits may be stimulus-specific since different abnormalities are observed between tone and language stimuli. Supported by a Cure Autism Now Foundation Grant. P3.4.3 SUPERIOR DISEMBEDDING IN INDIVIDUALS WITH AUTISM AND THEIR PARENTS: THE NEED OF SUBTLE MEASURES. M.V. de Jonge, C. Kemnerand and H. van Engeland*. Univ. of Utrecht, Depart. Of Child and Adolesc. Psych., Utrecht 3508 GA, The Netherlands In this study we assessed disembedding performance on the Embedded Figures Test (Witkin et.al., 1971) in high-functioning subjects with autism and autism spectrum disorders from multi-incidence families. In addition the parents of these subjects were assessed, as well as a group of control parents. The individuals with autism spectrum disorders were significantly faster than matched controls in locating the shape. Their fathers or mothers were not found to be faster than control parents. However, both the individuals with autism spectrum disorders as well as their fathers made significantly less incorrect attempts before finding the right shape. These results indicate that the number of attempts, is a more subtle measure for assessing superior disembedding skills and therefore useful in the assessment of individuals with spectrum disorders and the broader phenotype of autism. P3.4.4 LOCAL VERSUS GLOBAL PLANNING IN NARRATIVES BY CHILDREN WITH AUTISM . J.J. Diehl, L. Bennetto* and J.E. Arnold. Depts. of Clinical & Social Sciences in Psychology, and Brain & Cognitive Sciences, Univ. of Rochester, Rochester, NY 14627.

The current study examined sentence planning and story structure in narratives of a televised cartoon by children with autism. The position of dysfluencies in clauses has been found to be a marker of utterance planning in typical individuals. Global planning can be captured by examining story grammar, which divides narratives into basic components including context or preliminary structure (settings), description of concrete events (episodic), and character’s thoughts/emotions (mental state). Participants included 25 high functioning children with autism and 25 typically developing controls matched on age, gender, and VIQ. Participants watched a televised cartoon, which they retold to a naïve listener. Preliminary data revealed that, at the local level, children with autism produced sentences that were similar in length and complexity to controls. No group differences were found in the location of dysfluencies or the percentage of clauses with a dysfluency. At the global level, children with autism had significantly fewer clauses per narrative than controls (p<.02). Children with autism also had fewer settings in their stories than controls (p<.05), despite having no differences in episodic or mental state story grammar categories. Further analyses revealed a trend toward fewer orientation (description of context) and action (description of behavior) settings in children with autism. These data suggest that children with autism may have difficulty planning and structuring their story, but their ability to plan at the sentence level appears intact. P3.4.5 THE RELATIONSHIP BETWEEN NEUROPSYCOLOGICAL MEASURES OF COGNITIVE FLEXIBILITY AND STEREOTYPED AND REPETITIVE BEHAVIOR IN CHILDREN WITH AUTISM SPECTRUM DISORDERS. M.C. Gibbs, P. Lee, L. Gilotty, G. Wallace, D. Black and L. Kenworthy*. Center for Autism Spectrum Disorders, Children�s National Medical Center, Washington, DC 20010. This study investigated the relationship between repetitive and stereotyped patterns of behavior in persons with Autism Spectrum Disorders (ASD) and neuropsychological measures of cognitive flexibility. A clinically referred group of high functioning

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children with Autism, Pervasive Developmental Disorder-Not Otherwise Specified, and Asperger’s Disorder (n=28) were administered that Autism Diagnostic Interview (ADI) and a neuropsychological test battery. The Behavior Rating Inventory of Executive Function (BRIEF) Shift Scale and the California Verbal Learning Test- Children’s Version (CVLT-C) Perseveration Index were used as measures of cognitive flexibility. Multiple regression analysis indicated that the combination of neuropsychological indices of cognitive flexibility was predictive of ratings on the ADI Repetitive Behavior scale (R2 = .47, p < .05). These findings support a link between the neuropsychological concept of cognitive flexibility and the repetitive and stereotyped behavior in children with ASD. P3.4.6 EARLY VISUAL CORTEX ORGANIZATION IN AUTISM: AN fMRI STUDY. N. Hadjikhani, C. Chabris, R.M. Joseph, J. Clark, L. McGrath, I. Aharon, E. Feczko, H. Tager-Flusberg*, G.J. Harris. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. Autism is a neurodevelopmental disorder characterized by preserved visual abilities as well as a special profile for visual cognition. We examined the visual cortex of high-ability individuals with autism in order to assess whether the presence of abnormalities at the primary sensory level in autism could be the basis of their unusual pattern of visual cognitive abilities. We found that the early sensory visual areas are normally organized in individuals with autism, with a normal ratio between central versus peripheral visual field representation. We conclude that the differences observed in the visual capacities of individuals with autism are likely to arise from higher-level cognitive areas and functions, and are the result of top-down processes P3.4.7 COGNITIVE FUNCTIONING AND ASPERGER’S DISORDER: GIRLS VS BOYS . A.V. Hall, PhD., R.K. Abramson, PhD., S.A. Ravan, MS, H.H. Wright, MD* University of South Carolina School of Medicine, Columbia, SC, 29203 and M.

Cuccarro, PhD. Duke University, Center for Human Genetics, Durham, NC, 79910. This study compares the cognitive functioning of males and females with Asperger’s Disorder in order to evaluate whether there are differences between the two groups. Subjects were drawn from a molecular genetic study of Asperger’s Disorder. Diagnoses are confirmed using medical records and/or clinical evaluation and the Asperger’s Syndrome Diagnostic Scale. Asperger’s Disorder males (n=8) and females (n=8) were age matched within 12 months for chronological age at the time of completion of the cognitive measures. The Wechsler Intelligence Scales and the Delis-Kaplan Executive Function System were administered to measure cognitive functioning. The findings for the Wechsler Scales showed that the females scores were significantly higher than the males on the Verbal Comprehension Index (t(1,14)=2.207, p= .045) and the Comprehension subscale (t(1,14)=2.207, p= .045). The findings for the Delis-Kaplan Executive Function System showed that females scored significantly higher than the males on deductive reasoning tasks (t(1,14)=2.407, p= .033), hypothesis testing tasks, (t(1,14)=2.751, p= .018) and tasks that measure verbal fluency,(t(1,14)=2.282, p= .042). The previous literature suggests that overall females have better-developed verbal skills than males (Gleason & Ely, 2002). Given that these tasks are in the verbal domain, the differences between the sexes may be due to the fact that females are better able to express themselves than their male counterparts. Thus the findings of this preliminary study indicate that the same is true for individuals with Asperger’s. P3.4.8 EFFECTS OF RELATED AND UNRELATED CONTEXT ON MEMORY IN ASPERGER'S SYNDROME. D.M. Bowler, J.M. Gardiner and S.B. Gaigg. Department of Psychology, City University, London EC1V 0HB, UK Existing research has shown that individuals with autism experience difficulties in using relatedness among studied items to help their free recall (Tager-Flusberg, 1991; Bowler et al. (1997). People with autism have also been reported to have

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difficulties in recalling the source of studied material, even when recall of the studied material itself is unimpaired (Bennetto et al., 1996; Bowler et al., in press). Furthermore the theory of Weak Central Coherence (WCC, Frith & Happé, 1994) suggests that people with autism are impaired in their use of contextual information. On the basis of this literature we predicted that, unlike typical individuals, individuals with Asperger's syndrome would not show enhanced recognition memory for words presented alongside a related rather than an unrelated context word. A similar method was used by Mayes et al. (1992) to demonstrate that people with amnesia had a disproportionate memory deficit when interactive context was present. That is when non-studied material that was present at study and was conceptually related to the studied material. Our results did not support the hypothesis. Both groups showed the same advantage in recognition for words presented with related context words. The implications of these findings for theories of autism are discussed. P3.4.9 A FUNCTIONAL MRI STUDY OF RESPONSE INHIBITION IN AUTISM. R.K. Kana, T.A. Keller, M.A. Just* and N. Minshew+. Center for Cognitive Brain Imaging, Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213. +Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260. The act of inhibiting a prepotent response involves cognitive flexibility and requires the orchestrated participation of a number of distinct neural structures distributed throughout the brain. This study measures the brain activation in autism during a task that requires inhibitory control and performance monitoring. Adults with high-functioning autism and matched control participants were studied using functional magnetic resonance imaging during performance of a response inhibition task involving working memory. Subjects with autism showed less brain activation than controls in anterior cingulate cortex, particularly during inhibition, an area often found to be active in response inhibition tasks. On the other hand, subjects with autism showed more activation in frontal and parietal areas, especially the right superior parietal lobe and left

dorsolateral prefrontal cortex during inhibition than controls. The results indicate that the control group and the autism group might accomplish inhibition differently. While the control group seems to rely on a more automatic approach, based on the anterior cingulate system, the autism group seems to use the strategic prefrontal-parietal system. Source of Funding: NIH P3.4.10 EARLY VISUAL PERCEPTION IN INDIVIDUALS WITH AUTISM AND THEIR PARENTS. C. Kemner, M.V. de Jonge and H. van Engeland*. Univ. of Utrecht, Depart. Of Child and Adolesc. Psych., Utrecht 3508 GA, The Netherlands We assessed low level visual information processing in a group of high-functioning subjects with autism and autism spectrum disorders from multi-incidence families. In addition the parents of these subjects were assessed, as well as a group of control parents. We used a random dot kinematogram to assess motion coherence thresholds as a measurement of dorsal stream functioning. A form discrimination task was used to measure ventral stream functioning. Visual acuity was measured to be able to control for refractional impairments. We did not find differences between groups on any of the tasks, indicating that there were no low level visual impairments in our group of high-functioning individuals within the autistic spectrum or their parents in comparison to controls. P3.4.11 MINOR PHYSICAL ANOMALIES IN AUTISM AND IN MENTAL RETARDATION . M.M. Konstantareas, and E. Cooper. Department of Psychology, College of Social and Applied Human Scinces, University of Guelph, Guelph, Ont. Canada. More than two minor physical anomalies (MPA) have been linked to neuropathology. We examined MPA in 240 chilren, 125 with Autistic Disorder (AD), 55 with Mental Retardation (MR) and 60 matched controls. Demographic, symptom expression and functioning level data were included. Using the Waldrop et al. (1976) scale, we found a Kappa of .93, for 30% of the MPA data. A 3 (group) x 4 (head, mouth, hands and feet) MANOVA yielded a

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significant group effect (F, 2, 234 = 8.22, p <.001), with the two clinical groups showing a greater number of MPA than controls. ANOVAs for each of the 21 MPA, with Bonferroni adjustments for alphe levels, showed differences for 8 of the 21, across the three groups: multiple hair whorls, epicanthal folds, low-seated ears, adherent ear lobes, high arch palate, fifth finger curved, stubbed fifth finger and third toe longer than second. For total MPA, the MR group was the most affected (F, 2, 234 = 28.32, p <.000). Degree of symptom severity and level of functioning were not significant predictors of total MPA for either clinical group. The findings are discussed in the context of the relevant literature. The project was funded by the Social Sciences and Humanities Research Council of Canada to the first author. P3.4.12 PATTERNS OF PERFORMANCE ON THE LEITER-R IN YOUNG CHILDREN WITH AUTISM SPECTRUM DISORDERS, NON-AUTISM DEVELOPMENTAL DELAYS, AND TYPICAL DEVELOPMENT. E.S. Kuschner, L. Bennetto* and K. Yost. Univ. of Rochester, Dept. of Clinical & Social Psychology, Rochester, NY 14627. An uneven pattern of cognitive abilities has previously been demonstrated in individuals with autism spectrum disorders (ASDs). This study further examines this profile of intact and impaired abilities in young children with ASDs via the Leiter International Performance Scale - Revised (Roid & Miller, 1997). A nonverbal assessment like the Leiter-R allows identification of strengths and weaknesses that persist regardless of language abilities. Compared to the relatively flat Leiter-R profiles seen in typically developing children (Roid & Miller, 1997) and children with fragile X syndrome (Hooper et al., 2000), preliminary data (n=14) suggest that children with ASDs (4.42-7.42 yrs) show an uneven pattern of performance. Compared to their own subtest means, they show relative strengths on Figure Ground and Form Completion, and relative weaknesses on Sequential Order and Repeated Patterns (paired t-tests: FG, FC>SO, RP; p�s<.0001). Thus, preliminary findings suggest that intact PIQ scores often seen in autism are not due to broadly enhanced visuospatial abilities, but rather

are driven by unique skills in identifying a stimulus within a complex field. In contrast, children with autism showed greater difficulty processing complex or abstract information. Additional matched control groups of children with non-autism developmental delays and typically development are currently being collected to confirm the unique nature of this profile to autism. P3.4.13 PERFORMANCE ON CANTAB SUBTESTS SENSITIVE TO FRONTAL LOBE FUNCTION IN PEOPLE WITH AUTISTIC DISORDER: EVIDENCE FROM THE CPEA NETWORK. S. Ozonoff *, H. Coon, G. Dawson, R.M. Joseph, A. Klin, W.M. McMahon, N. Minshew, J.A. Munson, B.F. Pennington, S.J. Rogers, A. Spence, H. Tager-Flusberg and F.R. Volkmar. M.I.N.D. Institute, UC Davis, Sacramento CA 95817. Recent imaging, neuropathology and neuropsychology studies provide empirical support for the involvement of frontal cortex in autism. CANTAB is a computer-administered set of neuropsychological tests developed to examine specific components of cognition. Previous studies document the role of frontal cortex in performance of two CANTAB subtests, the Stockings of Cambridge, a planning task, and the Intradimensional/ Extradimensional Shift task, a measure of cognitive set shifting. These subtests were administered to 79 participants with autism and 70 typical controls recruited from 7universities who are part of the Collaborative Programs of Excellence in Autism (CPEA) network. The two groups were matched on age, sex, and Full Scale IQ. Significant group differences were found in performance on both subtests, with the autism group showing deficits in planning efficiency and extradimensional shifting relative to controls. Deficits were found in both lower- and higher-IQ individuals with autism across the age range of 6 to 47 years. Impairment on the CANTAB executive function subtests did not predict autism severity or specific autism symptoms, but was correlated with adaptive behavior. If these CANTAB subtests do indeed measure prefrontal function, as suggested by previous research with animals and lesion patients, this adds to the

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accumulating evidence of frontal involvement in autism. P3.4.14 RESPONSE INHIBITION AND STATE REGULATION IN CHILDREN WITH HFA AND ADHD. R. Raymaekers, I. Antrop, H. Roeyers, J.J. van der Meere, J.R. Wiersema, S. Verté and D. Baeyens. Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium, B-9000 The aim of the current study was to evaluate whether autism and Attention Deficit Hyperactivity Disorder (ADHD) can be distinguished from the perspective of response inhibition and state regulation and to test whether autism is associated with a deficit of overarousal, since suggestions have been made linking arousal regulation problems to autism (see f.i. Dawson & Lewy, 1989; James & Barry, 1980). Subjects in this study are normally intelligent (IQ>80) children, aged 7 to 12 years, with high-functioning autism (HFA). They are compared with normally developing peers and with children with ADHD, using a go/no-go paradigm wherein stimuli presentation is fast (2s), slow (8s) and self-paced. In 75% of the trials, an X appears on the screen and the subjects have to respond by pushing a button as quickly as possible. In the other 25% however, the letter O is presented and no response is required. The results suggest that performance efficiency (Mean RT, Standard Deviation of RT and Errors of Commission), with the exception of a lower mean reaction time, is the same in children with HFA as in the control group, but differs from the children with ADHD. Moreover, children who met both diagnostic criteria for autism and ADHD perform similar to the latter group. This work is supported by the Research Board of the Ghent University. P3.4.15 IS THERE A REGRESSIVE PHENOTYPE OF AUTISM SPECTRUM DISORDER ASSOCIATED WITH THE MEASLES-MUMPS-RUBELLA VACCINE? J. Richler, R. Luyster, S. Risi, C. Lord* and Collaborative Programs for Excellence in Autism.

A multi-site study of 357 children with Autistic Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews (i.e., the Autism Diagnostic Interview - Revised) at the time of entry into other research projects and follow-up telephone interviews designed for this project to describe the children’s early acquisition and loss of social-communication milestones as well as the presence of any gastrointestinal symptoms. For children with ASD, information about vaccination dates was obtained from the children’s medical records. Children who had acquired skills that they subsequently lost were described by their caregivers as showing a greater number of skills prior to the loss and fewer of these skills after the loss than other children with ASD. Children who had experienced losses also showed poorer outcomes in verbal IQ and social reciprocity (as measured on the ADI-R), a later mean age of onset of autistic symptoms, and a greater number of gastrointestinal symptoms than children with ASD without regression. There was no evidence to suggest that onset of autistic symptoms or of regression was related to MMR vaccination. The implications of these findings for the existence of a regressive “phenotype” of ASD are discussed. P3.4.16 EXECUTIVE FUNCTIONS IN AUTISM AND OTHER DEVELOPMENTAL DISORDERS. H. Roeyers (1), S. Verté (1), H. Geurts (2), J. Oosterlaan (2) and J.A. Sergeant (2). (1)Ghent University, Department of Experimental-Clinical and Health Psychology, Gent, Belgium; (2)Vrije Universiteit, Department of Clinical Neuropsychology, Amsterdam, The Netherlands In the present study we investigated if a specific neurocognitive EF-profile can differentiate between High-functioning Autism (HFA), Attention Deficit Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS). Some important innovations of this study in comparison to earlier studies can be mentioned. First, non-EF control tasks were used that have no relationship with the prefrontal region. Second, the children were compared on an extensive battery of EF tasks covering the most important EF domains. Most studies covered only two or three domains. Third, extensive diagnostic

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procedures were used, including parent and teacher questionnaires, and two structured interviews. The attempt to distinguish disorders in their EF profile can only be established with thoroughly defined clinical groups. Furthermore, only children who did not use medication participated in the study. Finally, unlike most studies comorbidity was taken into account. Results show that EF deficits are very characteristic of children with HFA, and also, but to a lesser extent of children with ADHD. The results suggest a re-evaluation of the EF hypothesis in TS. They also suggest that it is important to take comorbidity issues into account, especially the combinations of HFA with ADHD or with TS. P.3.4.17 IMPAIRED CATEGORICAL PERCEPTION IN AUTISM: AN ABNORMAL TOP-DOWN EFFECT. I. Soulières, L. Mottron, D. Saumier, and S. Larochelle. Clinique spécialisée de l’autisme, Hôpital Rivière-des-Prairies, Montréal, QC, CAN, H1E 1A4. Categorical perception occurs when there is a qualitative difference in the perceived similarity between stimuli, whether or not they are in the same category. Categories therefore have a top-down influence on discrimination of their members. C. Frith (2003) proposed a diminished top-down influence from upper perceptual processes on lower ones in autism. Our goal was to investigate categorical perception in participants with high-functioning autism and matched comparison participants, using a discrimination and a classification tasks with a continuum of thin to large ellipses. The two empirical indicators of categorical perception were obtained in the comparison group. First, their classification curve displays a S-shape: an equivalent distance between two stimuli results in large differences in classification proportion if close to the boundary between the categories, and minimal effects if distant from the boundary. Second, discrimination performance is superior near the boundary. By contrast, participants with autism displayed a typical classification curve, but no amelioration of discrimination near the boundary. This is the first demonstration of atypical categorical perception in autism. The representation

of the categories is similar in both groups, since classification curves are undistinguishable. However, there is an absence of influence of categories on discrimination performance among persons with autism, which suggests a reduced top-down influence at the category level. It may reflect a fundamental difference among individuals with and without autism in the lowest level of categorization processes.Funds: NSERC and SSHRC P3.4.18 INCREASED NON-RIGHT (LEFT) HANDEDNESS IN AUTISTIC INDIVIDUALS, THEIR PARENTS AND SIBLINGS. S.J. Spence, N. Gitcho, L.J. Sterling, C.M. Lajonchere and D.H. Geschwind*. Departments of Psychiatry & Neurology, David Geffen School of Medicine at UCLA and the Autism Genetic Resource Exchange, L.A., CA, 90095. Many studies have found increased percentages of left or mixed handedness in autistic individuals compared to the general population and other developmentally disabled populations. Theories regarding the reason behind this phenomenon included some form of early left hemispheric damage or perhaps an aberration in the development of the typical hemispheric laterality profile. However, both autism and handedness appear to have strong heritibility, yet the only 2 studies looking at handedness in family members found no significant shift in distribution compared to population norms. To further explore the possibility of altered cerebral dominance as a potential etiologic factor in autism we examined handedness profiles in the parents and unaffected siblings of autistic individuals. Handedness patterns from ~200 idiopathic multiplex autism families in the Autism Genetic Resource Exchange (AGRE) were analyzed. Categorical data for hand preference in autistic individuals was obtained via parent report (R, L, Ambi). Parents and unaffected siblings were given a modified Edinburgh questionnaire and a skill task. Autistic individuals had a significantly higher percentage of non-right handers than the general population norms. This was also true for the parents and unaffected siblings, in which left-handedness was nearly double the population prevalence. The

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significantly increased percentage of non-right handers in the parents and siblings of autistic probands suggests that altered cerebral dominance is a susceptibility factor for autism. P3.4.19 SPATIAL WORKING MEMORY DEFICIT IN AUTISM. S. Steele*, N. Minshew, B. Luna, and J.A. Sweeney. Cntr. for Cog. Med., UIC, Chicago, IL 60612 and Dept. of Psychiatry, Univ. of Pitt., Pittsburgh, PA 15213. Previous studies have reported working memory deficits in autism, but this finding has not been consistent. One possibility is that deficits in this domain may be present only in certain task conditions, such as when working memory load is high. Groups of 35 high-functioning individuals with autism and 28 healthy individuals, matched on age, Full Scale IQ, SES, and gender, were tested with the CANTAB computerized test of spatial working memory. Compared to healthy participants, individuals with autism made significantly more errors than healthy participants when performing this working memory task. Deficits in the autism group became progressively more pronounced when task conditions imposed increased working memory load. In addition, when searching for hidden tokens on the task, participants with autism used less organized search strategies. These results demonstrate a reduced capacity for maintaining information in spatial working memory and for systematically solving spatial problems in individuals with autism. These impairments suggest functional abnormalities in dorsolateral prefrontal cortical systems in autism. This study was supported by the National Alliance for Autism, the NICHD Collaborative Program of Excellence in Autism HD35469, NS33355, and MH01433. Poster Session 3: Topic 5: Neuropathology and

Basic Studies P3.5.1 METABOLOMICS IN AUTISM . B. Evans, J. Evans and O. Koul*. Department of Biochemistry and Molecular Pharmacology, UMass Medical

Center, and Shriver Center, 200 Trapelo Road, Waltham, MA 02452. In order to fully understand alterations in white matter in autistic individuals, we have initiated a program of metabolomics to analyze frozen corpus callosum. For this purpose, small molecules extracts from corpus callosum were mixed with a cocktail of internal standards containing tropic acid, d5-benzoic acid, 13C3-pyruvate, d2-GABA, d3-vanilmandelic acid, d3-homovanillic acid, and d5-phenylalanine. The mixture was derivatized to obtain per-N, O-acetyl-pentafluorobenzyl-O-methoxime esters. The esters were dried with nitrogen and re-dissolved in ethyl acetate before analysis by GC-mass spectrometry. We have compared corpus callosum from 4-6 year old autistic individuals with corresponding controls. Some differences in profiles between the controls and autistic individuals have been detected and will be discussed in relation to their impact on metabolism in the nervous system. The investigations were partly supported by a grant from the Stanley foundation. P3.5.2 NEUROPATHOLOGICAL CORTICAL AND CEREBELLAR ARCHITECTURAL ABNORMALITIES IN A CASE OF AUTISM. C.J. McDermott, A. Dean, A. Bailey and P. Luthert*. Institute of Ophthalmology, UCL, London. EC1V 9EL; University of Cambridge, Addenbrooke’s NHS Trust, Cambridge CB2 2QQ, UK; University of Oxford, Warneford hospital, Oxford, OX3 7JX, UK. We present the neuropathology of a previously undescribed case, which was characterised by marked cortical abnormalities. The patient was a 41 year old non-verbal female who was diagnosed with autism with probable severe mental handicap but no history of epilepsy. The intact unfixed brain weighed 1233g. The right hemisphere was fixed in 10% formalin, embedded in paraffin and stained with Luxol fast blue (14 mm thick sections) and haematoxylin and eosin (7 mm thick sections). Morphological analyses were performed at x40 magnification. The superior parietal lobe, the cingulate and the superior frontal gyrus showed abnormal laminar arrangement. Increased numbers of multi-polar neurons were seen in the molecular

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layer of the frontal cortex, the superior temporal gyrus, the superior parietal lobule and the pre-central gyrus. Other cortical abnormalities include abnormal spatial arrangement of large pyramidal neurons and areas of gliosis. There were abnormalities in the cerebellar vermis where Purkinje neurons were irregularly aligned and some occasionally misplaced. These data, in conjunction with that previously published (Brain (1998), 121, 889�905) provides further evidence of the diverse and distributed neuropathology of autism. Funding is provided by Medical Research Council, UK P3.5.3 A NEUROPATHOLOGICAL INVESTIGATION OF THE BRAINSTEM IN AUTISM. S. Thevarkunnel, M. Martchek, G.J. Blatt*, T.L. Kemper* and M.L. Bauman*. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118. We are currently analyzing the serial sections of the brain stems of five autistic individuals in comparison with five age-matched controls. Prior studies by Rodier et al. (1995) and Bailey et al. (1998) have called attention to several brain stem malformations, which may represent the earliest prenatal changes reported in the autistic brain. The aim of the present study is to determine if these or other malformations of the brain stem are a consistent finding. Specific emphasis will be placed on the abnormalities in the facial nucleus and superior olive noted by Rodier et al., and on the abnormalities noted in precerebellar nuclei and the locus coeruleus by Bailey et al. If found, consistent abnormalities would be of interest for several reasons: 1. These very early occurring changes could represent an initial chain of events, with the later occurring pathologies related to it. 2. They could be used for elucidating the genetic abnormalities in autism. The case report by Rodier et al. implicated specific gene abnormalities (HoxA1; HoxB1). The abnormalities reported by Bailey et al. were found in an inter-related set of nuclei that are derived from a single germinal zone (rhombic lip), with several genes implicated in the segregation, migration and settling of the neurons from this zone. 3. If a subset of these brain stems showed

consistent abnormalities, they could be related to the variability of the clinical presentation of autistic patients. The preliminary results of these studies will be presented. Tissue was provided by, TARF, the ATP via the BTBDD (Universities of Maryland and Miami), and the HBTRC. P3.5.4 CELL PACKING DENSITY IN THE INFERIOR OLIVE IN AUTISM. M.A. Ward, M.L. Bauman* and T.K. Kemper. Massachusetts General Hospital, Boston, MA and Boston University School of Medicine, Boston, MA. 02118 Previous studies of the autistic brain have shown significantly reduced numbers of Purkinje cells in the posterior inferior cerebellar hemispheres and age-related changes in the size of the synaptically related neurons of the cerebellar nuclei and in the Inferior Olive (IO). Because of the tight topographic relationship between Purkinje cells and the olivary neurons (Holmes and Stewart, l908), abnormalities of neuronal density in the IO (cells per unit volume) might be expected. The brains of one adult and two childhood autistic individuals were processed in Nissl stained serial sections and compared to age and sex-matched controls. Neuronal packing density within three IO segments was determined with StereoInvestigator in order to explore age-related changes in cell packing density in autism. The density of the IO neurons was significantly increased in the dorsal and lateral segment but not in the ventral segment of the adult autistic brain when compared with the control. In contrast, in the two childhood cases, the neuronal density was significantly reduced in all three IO regions when compared with controls. The topographic extent of the age-related changes in the IO is greater than would be expected given the restricted distribution of reduced numbers of Purkinje cells. This suggests that factors may contribute to the age-related changes in IO neuronal density. The cerebellar nuclei, which are also synaptically related to the IO, show similar age-related decreases in cell size. It is possible that the age-related changes in the IO may reflect this relationship.

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Funding provided by NIH/NINDS grant. P3.5.5 IMMUNOCYTOCHEMICAL ANALYSIS OF INTERNEURONS IN THE CEREBRAL CORTEX OF AUTISTIC PATIENTS. E. López-Hurtado and J.J. Prieto. Dept. Histology and Anatomy, Univ. Miguel Hernández, 03550-Alicante, Spain. We have previously reported a striking postnatal decrease (50%) in the number of cortical neurons in children with autism. The purpose of the present study was to determine whether this massive cell death affects equally all cortical neurons. We used tissue samples from the cerebral cortex of deceased autistic and control subjects and, by means of antibodies against the calcium binding proteins calbindin and parvalbumin we analyzed different subtypes of cortical interneurons. The somatodendritic and axonal morphology of double bouquet and chandelier cells was similar in autistic and control subjects at all ages studied. Yet, the density of chandelier cells decreased 70% in autistic patients between ages 7 and 30, whereas the reduction in the number of double bouquet cells was only 35%. Hence, there is a differential sensitivity of the distinct cell types to the pathogenic mechanism/s responsible for autism. Such imbalance in the proportion of inhibitory interneurons would result in a malfunction of the mechanisms that modulate the firing of the pyramidal cells. Supported by a grant of the Alliance for the National Autism Research. Brain samples were obtained from the Harvard Brain Tissue Resource Center, the University of Miami, and the Department of Pediatrics of the University of Miami at Baltimore. P3.5.6 CALBINDIN D-28K IS A RELIABLE MARKER FOR CEREBELLAR PURKINJE CELLS IN CONTROL AND AUTISTIC CEREBELLUM. E.R. Whitney, T.L. Kemper, M.L. Bauman, G.J. Blatt*. Boston University School of Medicine, Department of Anatomy and Neurobiology. Boston, MA 02118 We are reporting on an incidental but potentially important finding obtained when studying subpopulations of Purkinje cells (PCs) based on

calcium-binding protein expression. Formalin fixed cerebella were studied in 4 autistic and 3 age and sex matched control males (2 pairs;1 triplet ), ages 24-52 years. Microtome-cut serial sections were either thionin stained or immunostained for Calbindin D-28k (CB) and lightly counterstained with thionin. Tissue processing was identical for all sections within groups. Nissl sections were examined using stereological methods with the data expressed as the number of PCs per unit length (PCs/mm). Sections stained for Calbindin were analyzed using Neurolucida software as this program allowed us to obtain number of PCs/mm and PC location. In 5 of the 7 brains, there were no statistically significant difference (p=.75) in PC number between the thionin stained and CB stained sections and further, reveal that more than 99% of PCs stained for CB. In 2 brains, however, thionin stained sections revealed a statistically significant lower number of PCs as compared with CB stained sections (p=.04). These data suggest that agonal changes and/or the prolonged formalin fixation may impact the accuracy of PC counts using traditional thionin staining and that CB may be a better marker for determining PC number. Tissue was provided by: Harvard Brain Tissue Resource Center; Kathleen Price Bryan Brain Bank, Duke University Medical Center Supported by: NAAR, NIH NICHD (grant #:1R01HD39459-0182) P3.5.7 DENSITY AND DISTRIBUTION OF 125[I] LABELED 5-HT2A/2C RECEPTORS IN THE ANTERIOR CINGULATE CORTEX IN CONTROL AND AUTISTIC INDIVIDUALS. E. Antzoulatos and G.J. Blatt. Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, MA. The anterior cingulate cortex (area 24) is a key limbic structure which has an important role in socioemotional processing. It is one of the only cerebral cortical areas previously reported to have mild cytoarchitectonic abnormalities in the autistic brain (Bauman and Kemper, 1994). Area 24 is also marked by having specific binding patterns of the monoamine neurotransmitter serotonin, and this neurotransmitter is thought to help modulate many

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functions of area 24. Serotonin receptor types have an intricate role in the circuitry of area 24 and alterations in serotonin have been reported with respect to autism. In the current study, fresh frozen tissue blocks were cut and processed for receptor autoradiography from 10 control and 8 autistic cases. A multiple concentration saturation binding assay was conducted utilizing 125[I]DOI, an agonist for the 5HT-2a/2c receptor, to obtain total binding. Non specific binding was obtained using a displacer under the same assay conditions. Specific binding density and distribution in superficial and deep lamina will be analyzed using ImageJ software. Results from the entire data set will be presented. Tissue was provided by the Harvard Brain Tissue Resource Center, the Autism Tissue Program, the Harvard Brain and Tissue Resource Center, and the University of Miami Brain Bank. Supported by NIH STAART Center Grant U54 MH66398-01 and NINDS NS38975-01A1. P3.5.8 ENDOCRINE DISRUPTOR CHEMICALS: A POSSIBLE CAUSE OF AUTISM AND OTHER DEVELOPMENTAL BRAIN DISORDERS GENE EXPRESSION RESEARCH. Y-I. Kuroda. Tokyo Metropolitan Institute for Neuroscience, 2-6, Musashidai,Fuchu-shi, Tokyo183-8526, Japan. Some environmental chemicals including endocrine disruptors may be one of the causal factors of various developmental disorders of the brain, such as autism. Differnt exposure history of chemicals may cause differnt pattern of defects in neronal circuits, which can explain differnt conbination of synptoms observed in autismic and other disordered children.The thyroid hormone(TH) system is important for brain development and appeared as targets of PCB neurobehavioral toxicities. The insecticide pyrethroid, DDT and bisphenol A also represses activity-dependent BDNF gene expressions both in vitro and in vivo (Imamura, et al. J. Pharm. Exp. Ther.295, 1175, 2000). To observe different gene expression patterns in the functionally developing brain, we have developed an original highly quantitative DNA microarray only with 20% error, showing the different patterns of gene expression under different chemical environment. Dendrites extension of

Purkinje cells critically depends on TH, even under chemically-defined culture condition(Kimura-Kuroda, et al.,Develop. Brain Res,137, 55, 2002). TH also stimulates synapse formation among cerebral cortical neurons to make functional neuronal networks in culture. Very low doses (pM order) of PCB and hydroxy-PCBs inhibit TH-regulated gene expressions using a reporter assay system(Iwasaki et al. BBRC,299:384,2002), suggesting "DNA single target" hypothesis on the molecular mechanism of low dose effects (Kuroda, Environ. Sci. 10: 23, 2003). Similar low dose of hydroxy-PCBs also inhibits TH-dependent dendrite extension of Purkinje neurons in vitro. We are investigating the behavior of offsprings born to mother monkerys exposed to low dose of PCBs and hydroxy PCBs. P3.5.9 ALTERED CEREBRAL CORTICAL SPINE DENSITIES CHARACTERIZE A SUBGROUP OF INDIVIDUALS WITH AUTISM. H. Zhang and J. Hutsler *. Psychology Department and Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109-1109 In other disease states reduced spine numbers have been found in the cortex, including dementia (Ferrer et al 1991), Down syndrome (Marin-Padilla 1976), and schizophrenia (Garey et al 1998). Based upon studies of cortical size it has been suggested that autistic individuals may not show such reductions, and may actually show an increase in spine density (Mundy 2001). Pyramidal cells form long-range projections within the cortex and the morphology of these cells is best revealed in humans using Golgi methods. To study spine density on individual cortical pyramidal cells of autistic patients, regions from the superior parietal lobule (BA 7), lateral prefrontal cortex (BA 9), and middle temporal gyrus (BA 22) of autistic and age- and gender-matched controls were processed by a modified Golgi-Kopsch technique. Visible spines were counted along 25 µm lengths of apical, basal and oblique dendrites of pyramidal cells located in layers II, III and V of these three cortical areas. Measures associated with spine counts, including distance from the soma, dendritic diameter, and dendritic branch order, were also recorded. Preliminary results indicate that spine densities are

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higher in individuals with autism as compared to control subjects. Analysis of individual cases suggests that only a subgroup of our larger autism group shows this increase. We are currently exploring other factors that may be correlated with increased spine densities in this subgroup. This work is supported by the National Alliance for Autism Research, the Autism Tissue Program, the Harvard Brain Tissue Resource Center and the University of Miami Brain and Tissue Bank. P3.5.10 STEREOLOGICAL STUDY OF THE DEEP CEREBELLAR NUCLEI IN RATS EXPOSED TO VALPROIC ACID IN UTERO. T.L. Arndt, B.A. Tisdale, C.J. Stodgell, J.L. Ingram and P.M. Rodier*. Univeristy of Rochester School of Medicine and Dentistry, Rochester, New York, 14642. Our laboratory has previously reported similarities in neural structures between humans with autism and rats exposed to valproic acid (VPA) in utero. Exposure to VPA in utero is known to increase the risk of autism in humans. For this study, we examined two deep cerebellar nuclei using the VPA model. Pregnant Long-Evans rats received intraperitoneal injections of 600mg/kg sodium valproate on day 12.5 of gestation, and the offspring were sacrificed on postnatal day 40. The dentate and interpositus nuclei of twelve exposed offspring (6 male, 6 female) and eleven unexposed offspring (4 male, 7 female) were compared for differences in volume, neuron density and total neuron number. Compared to untreated animals, exposed offspring had a 30% reduction in the volume of the dentate nucleus (p<.01), and a 62% reduction in the volume of the interpositus nucleus (p<.01). The reduction in neuronal number was 23% in the dentate nucleus (p<.05), and 42% in the interpositus nucleus (p<.01). Consistent with previous studies, no differences in cell density were observed for either nucleus, and no significant sex differences were found. Decreased brain size (18% by brain weight) in treated animals may account for some of the results. These findings indicate a large treatment effect on the interpositus nucleus, and a modest treatment effect on the dentate nucleus. Results are consistent with human cases of autism, in which the globose & emboliform nuclei (homologous to the interpositus nucleus in

rats) are reduced, but the dentate remains unaffected. This work was supported by grants RO1HD34295 and U19HD35466. P3.5.11 DYNAMIC EXPRESSION OF MECP2 IN THE DEVELOPING MOUSE BRAIN. D. Braunschweig, T. Simcox, R.C. Samaco and J.M. LaSalle. Medical Microbiology and Immunology, Rowe Program in Human Genetics, UC Davis, CA, 95616 Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in MECP2, encoding the methyl-CpG-binding protein 2 (MeCP2). Despite ubiquitous transcriptional expression of MECP2, the onset of symptoms in RTT is delayed until 6-18 months and limited to the central nervous system. The onset of symptoms in the Mecp2-null mouse model of RTT is delayed until weeks in male and 4-6 months in female heterozygotes, developmentally later than expected from female RTT patients. To further understand the developmental dynamics of MeCP2 expression, we used laser scanning cytometry (LSC) to perform quantitative localization of MeCP2 in sagittal mouse brain sections during embryonic and postnatal development. While virtually all cells were positive for MeCP2 expression in wild-type mice, heterogeneity in the level of expression and chromatin localization was observed between different brain regions, developmental stages, and cellular subpopulations. A plateau in relatively high stable expression was observed from 3-6 wks, corresponding with the observance of a RTT phenotype in the Mecp2-null males. From 7-40 wks there was a positive correlation with age in the MeCP2 expression due to an increase in the MeCP2hi population. The continued increase in MeCP2hi cells during normal mouse adulthood may help explain the delay of symptoms in heterozygous female mice. In conclusion, these results demonstrate dynamic developmental regulation of MeCP2 and provide support to the hypothesis that MECP2 mutations are primarily manifested in the MeCP2hi population that emerges progressively during postnatal brain development. Supported by NIH/NICHD.

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Poster Session 3: Topic 6: Descriptive and

Diagnostic P3.6.1 PERCEPTIONS OF CHANGING NEEDS OF CHILDREN WITH AUTISM AMONG EDUCATORS IN SOUTH CAROLINA. J. Charles, L.M. Arnstein*, J. Nicholas, L.B. King, R. Brown and W.H. Jenner. Medical University of South Carolina, Charleston, SC 29414. Educators directly involved in service provision to children with autism in South Carolina (n=52 currently; data collection ongoing) were surveyed regarding their perception of changes in autism spectrum disorder (ASD) prevalence, current educational approaches, and evolving training and service needs. Respondents included direct care staff (61%) as well as non-direct care staff including special education directors and psychologists (39%). On average, providers had attended 2.3 classes or seminars that specifically addressed autism spectrum disorders. Forty-six percent of respondents believe there has been an increase in the number of students with ASDs in the last five years and 15% believe there has been a very large increase (more than a 10% increase). Indirect care staff was more likely than direct care staff to believe that there has been an increase in the prevalence of ASDs (X2 = 7.5, p=.006). While almost half of respondents indicated that applied behavior analysis instructional technology is currently being used in their school, 21% of respondents could not identify any specific educational approach being used. Data regarding other educational approaches currently being used and perceptions of training needs will also be presented. P3.6.2 DEVELOPING A CLINICIAN-FRIENDLY ASSESSMENT TOOL FOR A NATURALISTIC BEHAVIORAL INTERVENTION. M. Rocha, S. Dufek*, L. Schreibman and A. Stahmer. Autism Research Laboratory, University of California, San Diego 9500 Gilman Drive La Jolla, CA 92093-0109 The heterogeneity in treatment outcome for children with autism argues strongly for strategies to

prescribe treatment based on child characteristics. Studies in our laboratory have suggested distinct behavioral profiles that can be used to predict outcomes to a specific naturalistic treatment called Pivotal Response Training (PRT). These PRT profiles are based on six child behaviors found to be relevant to treatment response. These profiles have allowed us to predict which children will, or will not, benefit substantially from PRT. Children are classified as matching either the “non-responder” or “responder” profile. Although previous research has shown this profile to be predictive, the assessment of the profile requires time and materials that make it difficult to implement in clinical settings. The present study was designed to modify a research friendly, videotaped, interval scoring assessment from the laboratory to a “clinician-friendly” in-vivo, paper and pencil measure that is convenient to use in the natural environment. In this experiment, clinicians from the community came to our laboratory to score the assessment in vivo using the modified version of the scoring instructions. We evaluated the modified way of scoring to see if it was reliable with the original way by giving the child both forms of the assessment, the original version and the modified version. Then we compared the results yielded to confirm matching profiles. The child then received PRT in our laboratory to ensure that the profile was an accurate predictor of the child’s level of response to PRT. P3.6.3 LONG-TERM OUTCOMES OF CHILDREN WITH AUTISM SPECTRUM DISORDERS: A 5-YEAR FOLLOW-UP STUDY. B.J. Ivers*, R.L., Gabriels, L.G. Ogden and D.E. Hill. University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 Two previously defined groups (High versus Low developmental IQ) of children with ASD (n=14; mean age=10 yrs, 7 mos.) were re-evaluated after five years. There were no significant changes for either group in IQ estimates over time. The groups continued to differ significantly (p<.001) in NVIQ (Leiter-R) (High group > 97, Low group < 56). The groups also continued to differ significantly in adaptive functioning (Vineland Adaptive Behavior Scales) (High group mean= 67.4; Low group

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mean=27.7; p<.05), although a significant decrease (p<.001) was observed in both groups with an average 17.4 point drop over the five years. For both groups, the mean NVIQ score was 60% higher than the mean adaptive composite score. The groups also differed significantly (p< .001) in current estimates of one-word expressive (EOWPVT) and receptive (PPVT-III) vocabulary skills. Groups did not differ significantly in treatment intensity or amount of family involvement in child’s therapy. This study suggests that these children are receiving the same intensity of treatment services regardless of the severity of their NVIQ. The discrepancy between nonverbal cognitive ability and adaptive behavior scores appears to become more prominent as the children age. This study highlights the imperative need for creating appropriate treatment inventions that focus on the residual and widening deficits of these children. P3.6.4 DEVELOPMENT OF THE JOINT ATTENTION MEASUREMENT SCALE AND RESULTS OF SCALE RELIABILITY FROM PILOT DATA. K.A. Kerchner, C. Blevins and C.J. Claflin* Northwest Missouri State University 800 University Dr. Maryville, MO 64468 Objective was to develop a coding scale for coding joint attention behaviors of autistic children from post hoc videotape. The Joint Attention Measurement Scale (JAMS) was developed utilizing previous scales for joint attention that required modification in order to fully benefit coding behaviors from video. The scale has the capacity to measure comprehension, production, and interactive joint attention behaviors by the child. Production of joint attention by the autistic child is highly desired; therefore the scale further allows coders to denote whether the child’s attempts at joint attention are successful. Coders were then trained utilizing random samples of video clips. Pilot data and establishment of inter-rater reliability lends efficacy to the scale. Cohen's kappa was utilized to establish inter-rater reliability and the scale demonstrated a high reliability (K=.85-.88). Results indicate that the JAMS may be effectively utilized for coding joint attention behaviors from videotape. Applications of

the scale in early intervention programs will be presented. Sources of funding: Northwest Missouri State University Applied Research Grants #122424 & # 122160 to the principal investigator and College of Education of Human Services Undergraduate Research Grants and Education of Human Services Graduate Research Grants to student researchers. Distance traveled is 1649 miles. As full time students, graduate students are eligible to receive $250 in travel/conference money from the University per year and undergraduates $500, if funds have not been utilized for other University needs. P3.6.5 THE EFFECT OF HIGH AND LOW STRUCTURED CLASSROOM ACTIVITIES ON THE SOCIAL BEHAVIOR OF CHILDREN WITH AUTISM. A.C. Morgan and B. D’Entremont. University of New Brunswick, Fredericton, New Brunswick, Canada, E3B 2Y1 This study examined the effect of high (teacher-led) vs. low (free-play) structured preschool classroom activities on the social behaviour of children with autism and their typically developing peers. Thirty preschool children (15 with autism, 15 typically developing) were observed in a total of 25 different preschool classrooms. Children’s levels of pro-social behaviours (looking, talking, imitating) and anti-social behaviours (aggression, ignoring, self-stimulation) were recorded during high and low structured activities. Analysis indicated that significant differences in children’s social behaviour existed in relation to high vs. low structured activities and also as a function of group (typical vs. children with autism). These finding have implications for the development of preschool classroom curricula for young children with autism. P3.6.6 EDUCATIONAL PLACEMENT OF CHILDREN WITH AUTISM: RESULTS FROM A LONGITUDINAL STUDY. R.S. Oti, C. Lord*, S. Risi, C. Carlson and D. Anderson. University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109.

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Full inclusion of students with autism has been promoted as a means to help improve self-esteem, decrease stigma, and increase social skills by giving students with autism a chance to learn, either directly or through modeling, from typically developing peers. However, very few studies have been conducted to examine whether or not inclusion is associated with the desired effects for children with autism spectrum disorders. Because of the unique challenges children with autism face, the results of prior studies examining inclusion and students with learning disabilities may not apply to students with autism. The present study used data from a longitudinal study, which followed children who were referred for possible autism from under three years of age through fifth grade. First we examined the characteristics of children with autism in five different classroom settings at ages three and nine: 1) full inclusion class (n = 36, based on first grade placement), 2) regular education class with pull-out for resource room (n = 10), 3) regular education class with a one-on-one aide (n = 7), 4) multicategorical special education class (n = 55), and 5) autism-specific special education class (n = 32). Second, we examined the relationship between type of educational placement and social, cognitive and communicative development. We found, for example, that students who were in full inclusion classes in first grade had significantly higher socialization scores at age three than the children in the other four classroom placements. Further results will be presented. Poster Session 3: Topic 7: Families P3.7.1 INFLUENCES ON MATERNAL AND FAMILY FUNCTIONING IN CHILDREN WITH AUTISM SPECTRUM DISORDERS. S. Bishop, C. Lord, S. Risi, S. Qiu, D. Anderson. University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI 48109. Although extensive literature has addressed the impact of autism spectrum disorders (ASD) on the child, few studies have investigated the impact of having a child with ASD on caregivers. As part of an ongoing longitudinal study, mothers of children with

ASD (N=144) were administered the Child and Adolescent Impact Assessment (CAIA; Messer, Angold, Costello, & Burns, 1996) in order to assess the degree to which having a child with ASD impacts various domains of the mother’s functioning (e.g. finances, mental health). Total scores from the CAIA were calculated, and analyses were conducted to determine if specific child characteristics (e.g. gender, IQ) and family demographic variables (e.g. parent marital status, maternal education level) affect mothers’ perceptions of how their children with ASD impact personal and family functioning. Preliminary analyses indicate that child verbal IQ is negatively correlated with scores on the CAIA (i.e. mothers of children with higher IQ scores perceived their children as having less of an impact). However, child adaptive functioning, as measured by the Vineland Adaptive Behavior Scales (Sparrow, Balla, Cicchetti, 1984), was not related to CAIA total impact scores. Demographic variables, including child race, child gender, and maternal education level, were also not found to be associated with total scores on the CAIA. Future analyses will consider the role of additional demographic variables and will look at individual item scores on the CAIA. P3.7.2 PERSONALITY AND PSYCHOPATHOLOGY IN RELATIVES OF SUBJECTS WITH AUTISM. S Bölte and F. Poustka. Department of Child and Adolescent Psychiatry. J.W.Goethe-University, Frankfurt/M, Germany. The existence of a broader phenotype of autistic disorder characterized by a pattern of subclinical social, affective and cognitive impairments is postulated in behavior genetic research. With respect to the latter, the aim of this study is to examine whether certain personality traits and psychiatric symptoms are specific to relatives of individuals with autism. Eighty six relatives of subjects with autism, 22 of subjects with schizophrenia and 30 of subjects with obsessive-compulsive disorder completed the Symptom-Checklist (SCL-90-R) and the Personality-Style and �Disorder Inventory (PSSI). These three groups were compared on all 9 scales of the SCL-90-R and 14 of the PSSI using two-way (group, gender) simultaneous ANCOVAs, adjusted for effects of age

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and applying a Bonferroni corrected alpha of p<.0022. Only on the scale “Reserved-Schizoid” of the PSSI relatives of subjects with autism (especially fathers, T=59) score significantly higher (T=54.2) than parents and siblings of subjects with schizophrenia (T=48.1) and obsessive-compulsive disorder (T=49.4)[F2,131=8.36, p<.001]. Our findings indicate that mildly increased schizoid behavior could be a part of the broader phenotype of autism in relatives. Moreover it seems that compared to relatives of other mentally disordered subjects above average schizoid features are somewhat specific for this group. P3.7.3 SOCIAL-EMOTIONAL DIFFERENCES IN HIGHER FUNCTIONING CHILDREN WITH AUTISM. C. Burnette, D. Charak and P.C. Mundy*, Department of Psychology, University of Miami, Coral Gables, FL, 33146. In contrast to social cognitive theory some higher functioning children with autism (HFA) report an awareness of their impaired social interactions with others and associated dysphoria (Barnhill, 2001; Meyer et al. 2003). This study examined whether their self-reports of dysphoria and social impairments reflected a reliable difference among HFA children. The study also examined whether family factors were related to these differences. Twenty-two HFA children (9 to 15 years) participated in this study. Children’s self-reports on the Behavioral Assessment System for Children (BASC) and on the Social Anxiety Scale for Children (SASC-R) displayed significant test-retest reliability. Moreover, mothers’ self-report of their own social anxiety was related to child reports of Social Avoidance on the SASC-R (r = .46, p < .05) and a comparable “Social Stress” measure on the BASC (r = .86, p < .001). In addition, mothers’ reports of mood disturbance were related to children’s reports of “Fear of Negative Evaluation by Others” on the SASC-R (r = .44, p < .05) and “Unusual Thoughts and Perceptions” on the BASC (r = .60, p < .05). Mothers’ total symptom distress on the SCL-90 was also related to lower child ratings of satisfaction with “Relations with Parents” on the BASC (r = -.52, p < .05). Neither verbal nor performance IQs were related to children’s self report on the BASC or

SASC. Thus, HFA children display reliable individual differences in self-reported dysphoria and awareness of their own social limitations. These significant differences in clinical presentation may be linked to family factors. P3.7.4 CAREGIVER STRESS AND CONCERNS AS RELATED TO AUTISM FEATURES. D.E. Hill, R.L. Gabriels*, L.G. Ogden, B.J. Ivers.*University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262 We examined relationships between caregiver reported stress and autism features including sleep problems, level of adaptive functioning, and presence of maladaptive behaviors. Parents of children with an autism spectrum disorder (n=14, mean age = 10 yrs., 8 mos.) were asked to rate their level of caregiver stress using a 4-point likert scale for separate child characteristic domains. Participants were recruited from an earlier autism outcome study. Caregiver ratings of stress levels and the presence of sleep problems (r = .56; p = .03), adaptive functioning levels (Vineland Adaptive Behaviors Scale) (r = -.66; p = .010), and repetitive behaviors (Repetitive Behavior Scale - Revised)(r = .84; p = <.001) in their children were highly correlated. Additionally, caregiver reported current concerns for their children included friendships, academics, communication, and aggression. Caregiver concerns differed by level of nonverbal intellectual functioning (Leiter-R) of their child. Results suggest parental stress in this population is not solely related to autism core behaviors, but is influenced by the presence and severity of associated features. Type of caregiver concern provides information regarding population intervention needs. P3.7.5 PARENT PERCEPTIONS ON THE CONGENITAL VS. REGRESSIVE ONSET OF AUTISM AND ITS RELATION TO PARENTAL AFFECTIVE PSYCHOPATHOLOGY. R.P. Goin and B.J. Myers. Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284.

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Current research on the emergence of autistic symptoms during the first two years of life suggests that approximately 50% of affected children develop autism in a regressive fashion that follows a period of typical development, while the remaining half are described as having autistic-like characteristics since birth or shortly thereafter. The mechanisms behind these two developmental trajectories of autism are not understood. However, it has been proposed that the regressive form of autism is related to familial affective psychopathology. Several works note a higher incidence of autism in children whose first- and/or second-degree relatives present with affective disorders, but there has not been an examination of how such a family history relates to the type of onset (congenital vs. regressive) children experience. Data were collected through an internet questionnaire from 393 parents of children with autism-spectrum disorders. Open-ended responses concerning (a) self-reported diagnoses and family-history of mental-health disorders and (b) the type of autistic onset children experienced were coded and analyzed. A chi-square test of homogeneity indicated that a child coming from a parent with an affective disorder was more often described as exhibiting congenital autism (70%) than a child coming from a parent without an affective disorder (47%). Findings, methodological limitations, and future directions are discussed. P3.7.6 NEUROPSYCHOLOGICAL FUNCTIONING OF SIBLINGS OF CHILDREN WITH AUTISM. T. Pilowsky, N. Yirmiya, V. Gross-Tsur and R.S. Shalev. Hebrew University of Jerusalem, Jerusalem, Israel 91905; Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel 91031. Neuropsychological functioning of siblings of children with autism was examined to explore possible markers specific to the genetic liability for autism, as part of the broad phenotype of autism. Thirty siblings of children with autism, 28 siblings of children with mental retardation of unknown genetic etiology (MR), and 30 siblings of children with developmental language delay (DLD) were compared. Groups were matched by siblings’ age, gender, and birth order, probands’ gender, and mental age, family size, ethnicity, income, and

employment. Siblings of children with autism achieved higher Arithmetic (WRAT-III) scores than siblings of children with DLD. Of 14 siblings who received clinical diagnoses, cognitive disabilities were more prevalent in the DLD group than in the autismgroup. After excluding the diagnosed siblings, no differences emerged among the groups. Within the autism group, siblings' birth order was identified as an important characteristic related to siblings' functioning. Therefore, as most siblings of children with autism did not show specific neuropsychological deficits and did not differ from siblings of children with other neurodevelopmental disorders, neuropsychological functioning did not convey specific characteristics related to the genetic liability associated with autism. * This research was supported by the US/Israel Binational Science Foundation, the Israel Foundations Trustees, Diller Foundation, the Silvia and Milton Bard Fund for Pediatric Neuropsychology, and the Levin Center for the Normal and Psychopathological Development of the Child and Adolescent P3.7.7 THE SECOND CRISIS: PARENTING A PREPUBESCENT CHILD WITH AUTISTIC SPECTRUM DISORDER. M. Souders, J. Bloch, E. Giarelli, J. Pinto-Martin, S. Levy and PA-CADDRE. Autistic Spectrum Disorders (ASD) are neurobiological disorders affecting the social, communicative and behavioral streams of development. The middle school years mark a time of emerging independence, development of abstract thought and a shift in social demands on children. Despite advancements in treatments and counseling services, as children with ASD enter the prepubescent years, parents' repot a resurgence of grief and feelings of worry and isolation. The purpose of the hermeneutic phenomenolgical study is to describe the meaning of parenting a prepubescent child with ASD. A convenience sample of twenty parents of children, ages 10-12, with ASD will be interviewed by a pediatric nurse practitioner at the regional autism center in the Eastern US. Open-ended, in-depth interviews, lasting 1-1.5 hours will be audio-taped. Transcribed narratives will be read as a whole, then micro-

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analyzed to generate units of meaning. Finally, concepts will be grouped by theme. Paradigm cases will be generated. Two interviews are completed with mothers of 10 year old sons. Analysis of transcribed narratives uncovered a preliminary theme of "resurfacing of feelings of devastation and worry" for both mothers. The social demands on the 4th grader and parents thoughts of the transition to middle school renewed mothers' concerns about their child's ability to navigate the resposibilities of adulthood and challenged their hope for their child's independence. After the first crisis of the initial diagnosis of ASD, these mothers are experiencing a second crisis, the prepubescent years. Findings will offer insights on the "lived experience" of parents during this developmental transition. P3.7.8 FACTORS ASSOCIATED WITH THE BEHAVIORAL AND EMOTIONAL ADJUSTMENT OF SIBLINGS OF CHILDREN WITH ASD. A. Weissman*, B.A., J. Pinto-Martin, MPH, Ph.D. and the PA-CADDRE; Univ. of Penn., Philadelphia, PA 19104 While little research has been done on the psychological and behavioral health of siblings of children with ASD, there is some evidence to suggest that brothers fare more poorly than sisters. The purpose of this project is to identify those factors that predict psychological and behavioral adjustment in siblings of children with ASD and to determine whether these factors vary by gender. A request for participation was sent to members of the Autism Society of America and interested parties were told to contact the primary investigator via email. The PI emailed or faxed consent, assent, and information documents. Upon receipt of these forms, an interview was scheduled for the siblings and written questionnaires were sent to the parents via fax or email. The parents completed 2 questionnaires concerning family demographics and family functioning and the Child Behavior Checklist (CBC-L) (Achenbach, 2001). Siblings completed a telephone interview concerning their brother/sister with ASD and family interactions. To date, 68 families have contacted the PI to participate. Eight parents and siblings (7 brothers; 1 sister) have completed the questionnaires. Of the 8 siblings, 3

have a sister and 5 have a brother with ASD, and 4 of the 8 are younger than the child with ASD. Preliminary results on the CBC-L indicate that 2 (of 8) siblings are exhibiting clinical or borderline levels of externalizing/internalizing behaviors and 3 (of 8) siblings are showing clinical or borderline levels of academic or social adjustment. Future analyses will consider whether certain family characteristics or sibling perspectives predict normal psychosocial health. P3.7.9 DESCRIPTIVE ANALYSIS OF FAMILIES OF AUTISTIC CHILDREN WITH SEIZURES. L.W. Wang and S.J. Spence.* David Geffen School of Medicine at UCLA, L.A., CA 90024. Studies have shown increased prevalence of seizures in autistic individuals (5-38%). We describe the incidence of seizures in a subset of 200 families from the Autism Genetic Resource Exchange (AGRE). Approximately 20% of families met criteria for at least one family member with seizures or an abnormal EEG and were further analyzed. Our sample included 82 subjects with autism, 46 of whom experienced seizures. There were 28 unaffected siblings, 5 of whom had seizures, and 44 parents, of whom 8 mothers and 2 fathers had seizures. One-third of these families had 2+ family members with at least one seizure. Of the autistic subjects, 73% had true epilepsy, 20% had febrile seizures, and 7% had questionable spells that were probably seizures. In epilepsy pts, CPS and GTC alone or in combination with other seizure types were most common. Examination of EEG results showed that almost all autistic children with epilepsy underwent EEG and 40% had epileptiform abnormalities. A large percentage of autistic children without seizures also had EEGs with 30% being abnormal. Other related variables (seizure onset & severity, labs, imaging) will be further discussed. Consistent with the literature, we found a higher percentage of seizures and epilepsy in autistic probands and family members in the AGRE sample. The incidence of epileptiform abnormalities was somewhat lower than expected in epilepsy patients, but higher than expected in the autistic siblings without seizures. Further work must be done to elucidate if there is a common genetic factor in the

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pathophysiology of autism and epilepsy. The implications for the possible genetic susceptibility of autism and epilepsy will be presented. Slide Session 4: Topic 1: Theory of Mind S4.1.1 ATTACHMENT AND FRIENDSHIP IN AUTISM. N. Bauminger, S.J. Rogers and M. Solomon. Bar Ilan Univ. Sch. Of Education, Ramat Gan, Israel 52900. The present study aims at expanding our understanding regarding the ability to form social relationships in autism, by examining the link between attachment qualities relating to two developmental stages (toddlerhood and middle childhood); friendship qualities with a best friend and theory of mind in 17 (8 to 12) high-functioning children. Results demonstrated that 9 children (53%) perceived themselves as secure attached during middle childhood. Secure versus insecure group perceived their relationship with their mother as higher on trust and commuincation and lower on parents’ alienation. At toddlerhood; 7 children were perceived by their mothers as secure (41%); 7 insecure-avoidance (41%), and 3 disorganized (18%). Nice agreement was found between the two attachment measures. Nine children (53%) revealed continuity in their attachment style from toddlerhood to middle childhood (4 as secure and 5 as insecure). Eight children changed their attachment style; 3 (37%) to insecure and 5 (62.5%) to secure. Attachment security at middle childhoood significantly correlated with intimacy, help and conflict in friendhsip with peers. Higher degrees of intimacy and help and lower degrees of conflict were reported by the secure children. First and 2 nd order theory of mind capabilities were similar in the secure and insecure group, however, the secure group tend to provide more complex justifications to the false - belief question. Study results are discussed with regards to the development of internal working models of affective relationships in high-functioning children with autism.

S4.1.2 IMPAIRED COMMUNICATION IN AUTISM: THE ROLE OF IDENTIFICATION. P. Hobson, T. Lee and J. Meyer. Developmental Psychopathology Research Unit University College London and Tavistock Clinic 120 Belsize Lane London NW3 5BA UK Suppose you had difficulty identifying with other people. How would you communicate with them? We devised a three-person situation to address this question, as it relates to individuals with autism. Participants were 12 children and adolescents with autism, and 12 non-autistic children with learning difficulties. Groups were matched according to chronological age and verbal ability. We predicted group differences insofar as children with autism would a) copy gestures to relay a message, but without adopting the demonstrator’s style; b) have difficulty shifting roles between learner and teacher; c) show less experience sharing/joint attention; and d) manifest less emotional engagement with the investigators. The children were shown an action by a first investigator, and were asked to get a second person to do the same action. The demonstrations included four goal-directed actions with objects, and two that involved only gestures. The results were in keeping with each of our predictions. Despite attention to the demonstrations, participants with autism were less likely to adopt style, shift roles, share experiences, and engage emotionally. Behavioural ratings indicated that they showed less frequent looking and smiling. We interpret these results to suggest that autism involves a weaker propensity to identify with the subjective experiences of others. This may be critical for developing new approaches to foster their communicative abilities. This project was funded by the Economic and Social Research Council (ESRC). S4.1.3 EMPATHISING AND SYSTEMISING IN ADULTS WITH AND WITHOUT ASPERGER SYNDROME. J. Lawson, S. Baron-Cohen* and S. Wheelwright. University of Cambridge, Autism Research Centre, Department of Psychiatry, Douglas House, Trumpington Road, Cambridge, CB2 2AH, U.K.

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Empathising and systemising are postulated cognitive dimensions that have emerged from within the Theory of Mind / folk psychology/folk physics model of autism. An experiment was devised to compare ability in these areas between adults with and without autism spectrum conditions. Three groups of participants (matched on IQ and age) took part in the study: males with Asperger syndrome (n= 18); “normal” males (n=44); and “normal” females, (n=45). Each participant completed a task that involved empathising and a task that involved systemising. On the empathising task, normal females scored significantly higher than normal males, who in turn scored higher than the males with Asperger syndrome. Conversely, on the systemising task, normal females scored significantly lower than both of the male groups; the male groups did not differ significantly from each other on this task. These results support the idea that autism spectrum conditions involve a deficit in empathising allied to a normal level of systemising ability. They are also in line with the “extreme male brain” theory that places autism spectrum conditions at an extreme point along a continuum of cognitive styles that includes the general population. The findings also have implications with regards the Executive Function and Central Coherence models of autism. S4.1.4 AUTISM AND THE ROLE OF “CULTURAL KNOWLEDGE” IN USING THEORY OF MIND IN PRACTICE. E. Loth 1,2*, J.C. Gómez 2. 1SGDP Centre, Inst of Psychiatry, London, SE58AF, U.K. 2School of Psychology, Univ of St Andrews, KY169JU, Scotland The theory of mind (ToM) deficit hypothesis has difficulties explaining why individuals with an Autism Spectrum Disorder (ASD) often adhere to inflexible routines and why a high-functioning minority who passes experimental ToM tasks shows characteristic social dysfunctions. Study 1 explored abnormalities in representing event scripts that are necessary to effectively use ToM competencies in practice. Qualitative and quantitative analyses of event narratives showed that lower-functioning ASD had severe impairments in the general, temporal-sequential and hierarchical structure of scripts.

Script abnormalities in high-functioning ASD included low-level “slotfiller” descriptions and significantly fewer linguistic qualifiers. Study 2 investigated the relation between Weak Central Coherence (WCC), a piecemeal processing style, and the hierarchical organisation of scripts. Participants with ASD and controls were subdivided into CC groups and asked to rate the occurrences of central, optional and inappropriate acts. ASD with WCC rated optional acts that could occur significantly more often as occurring always/ never than controls. It is suggested that the analysis of cultural knowledge abnormalities provides a mediator between core aspects of the non/social phenotype of ASD and cognitive abnormalities with which ToM functions are articulated. The possibility that in ASD, event perception might be less concept driven and repercussions of script abnormalities for memory of experiences will be discussed. *This research was supported by a studentship from the Univ of St Andrews, and a research fellowship from the Econ and Soc Research Council, U.K. S4.1.5 SELF-OTHER ORIENTATION IN AUTISM. J. Meyer and P. Hobson. Developmental Psychopathology Research Unit, University College London and Tavistock Clinic, 120 Belsize Lane, London NW3 5BA UK This study was designed to test the hypothesis that children with autism would show specific disability in identifying with the subjective orientation of another person. We predicted that children and adolescents with autism, relative to chronological and verbal mental age matched non-autistic peers, would have a lesser propensity to adopt the self-other orientation of another person when imitating actions, even when other aspects of the actions were imitated successfully. Sixteen children with autism and 16 matched non-autistic children with learning difficulties or developmental delays participated. There were four actions, each demonstrated in one of two possible orientations-toward self or other-in a first visit, and the alternative orientation in a second visit. Results accorded with our predictions, suggesting that participants with autism were not impaired in their ability to copy other aspects of the simple actions modelled, but were

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instead atypical in their imitation of the person who modelled the actions. We consider the implications of these findings for the development of interpersonal understanding. This project was funded by the Economic and Social Research Council (ESRC). S4.1.6 MIND-READING IN YOUNG ADULTS WITH A PERVASIVE DEVELOPMENTAL DISORDER: DOES STRUCTURE MATTER? K. Ponnet, H. Roeyers, A. Buysse and A. De Clercq. Department of Clinical Psychology, Research Group, Developmental Disorders, Ghent University, H. Dunantlaan 2, B-9000 Gent, Belgium, Phone: +32-9-264 91 05 ; Fax: 32-9-264 64 89. This study investigates the mind-reading impairments of young adults with PDD. The hypothesis is that differences in mind-reading abilities between subjects with PDD and control subjects become more apparent when they have to infer thoughts and feelings of other persons in a less structured or more chaotic conversation, than when they have to do so in a more structured conversation. To test this hypothesis, we developed a naturalistic Empathic Accuracy Task, in which subjects viewed two videotaped interactions depicting two strangers and attempted to infer the thoughts and feelings of these persons. The videotaped interactions were manipulated in such a way that the conversation in one of the videotapes was less structured than in the other. The results suggest that subjects with PDD have poorer mind-reading skills than control subjects when confronted with the less structured conversation. No between-group differences were found when subjects had to infer the thoughts and feelings of other persons in the more structured conversation. The relationship between these findings and the degree to which individuals show autistic traits and perform on other mind-reading tasks (e.g. the Eyes Task) will be further discussed.

Slide Session 4: Topic 2: Cognitive Pocesses S4.2.1 DECISION-MAKING DURING A SIMULATED GAMBLING TASK IN ASPERGER’S DISORDER. S.A. Johnson*, E. Yechiam, R.R. Murphy, H.L. Coates, P. Theiner-Schumacher, J.D. Lutgring, R.E. Burt, and J. Stout. Clinical & Cognitive Neuroscience Lab, Indiana University, Bloomington, IN, 47405. The Bechara Gambling Task (BGT) is a simulated gambling task that elicits the interplay of learning, memory, and motivational factors, and which uses actual monetary payoffs. Because cognitive and motivational processes are of interest in autism spectrum disorders, we examined the BGT in 10 participants with Asperger’s Disorder and 10 typically developing volunteers matched for age (range 13 - 20 years), gender (6 male/4 female), and IQ (range 85 - 128). Participants made 150 selections from four computerized card decks (two advantageous and two disadvantageous) while their skin conductance responses (SCRs) were monitored. Each selection yielded feedback about wins ($0.25 or $0.50) and losses (up to $5.75). The most striking result was that, with very high reliability, the Asperger participants showed heightened indecisiveness, defined as few consecutive selections from the same deck. The longest consecutive run of choices from the same deck was 3.5 in Asperger participants (range 2 to 9) and 34.6 (range 3 to 99) in controls (p<.01). Whereas controls typically demonstrated preference for a particular deck as the task progressed, Asperger participants fluctuated between decks throughout the task. Notwithstanding, the Asperger group did learn to have fewer choices from a disadvantageous deck, although at a slower rate than the control group. Findings are discussed in the context of previously reported associations between indecisiveness, decision-making, and obsessive-compulsive symptoms. Skin conductance data will be examined to investigate associations between performance and autonomic responses.

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S4.2.2 POOR INHIBITION OF DISTRACTERS IN POP-OUT COUNTING: EVIDENCE FOR IMPAIRED ATTENTION IN AUTISM. M. Knobel and K. Boser. Johns Hopkins Univ., Baltimore, MD., 21287. Visual search studies in autism have claimed superior item discrimination and distracter inhibition based on faster responses in serial but not parallel search conditions. Yet, these abilities were not tested in tasks requiring overt target attention. In a task involving overt attention for target number, subjects with autism and controls were asked to count Os among Xs (Parallel “pop-out” process) or Os among Qs (Serial process), varying distracter number. Both groups were slower for serial relative to parallel conditions. Control subjects and some subjects with autism showed the predicted evidence for “pop-out”, i.e., counting < 3 targets equally quickly (subitization) and no effect of distracter amount on counting. However, several subjects with autism were affected by distracter number in pop-out search, suggesting serial processing for both conditions. These subjects also counted large numbers faster for pop-out but not conjunctive search, potentially resulting from easier discrimination of Xs from Os. In another counting task with no distracters, all subjects with autism showed subitization and faster large number counting than controls. Contrary to previous findings, our results suggest no better item discrimination than controls and difficulty ignoring distracters in subjects with autism, converging with recent evidence for poor irrelevant feature inhibition using negative priming. Together with our prior research using hierarchical figures, we argue that manipulation of target/distracter feature saliency is crucial in understanding attention breakdown in autism. S4.2.3 ARE PEAKS OF ABILITY REFLECTING A "G" FACTOR IN PERSONS WITH AUTISM? L. Mottron*, M. Dawson, C. Bertiaume, I. Soulière. Clinique spécialisée de l'autisme, Hôpital Rivière des Prairies, 7070 Bvd Perras, Montréal, Québec, Canada, H1E1A4.

Context. Peaks of ability may be the unique possible measure of intelligence in individuals with autism. However, models of hyperfunctionning in autism (Mottron & Burack, 2001) suggests that these peaks are not performed identically in persons with and without autism. This study investigates how peaks of ability are correlated with other measure of intelligence. Method: The participants with Autism, Asperger syndrome, and without PDDs of Rivière-des Prairies's database, for whom complete data of WISC-3, WISC-R, and WAIS were available, were enroled in this study. Peaks and valleys were individually computed as a difference (p <.05) of a specific subtest in relation to the average of other subtests. Correlations of the main peaks (e.g. Block-design, vocabulary) with VIP, PIQ, and FSIQ were computed for each population/instrument subgroup Results: peaks of ability in autism are correlated with values of intelligence in persons with and without autism. The more intelligent a person is, the higher his peaks are. However, when using instruments normalized for a non-autistic population in persons with autism, a correction factor has to be used to compute the value of general intelligence. Discussion: These findings suggest that peaks of ability may be used as a measure of general intelligence in persons with autism when a correction factor is used. A second conclusion is a "g" factor is shared by most cognitive operations measured by intelligence tests in persons with and without PDDs. However, this does not lead to the conclusion that non autistic and autistic "g" factors are identical. S4.2.4 DEGREE OF GLOBAL / LOCAL PROCESSING IS RELATED TO COHERENT MOTION DETECTION. E. Milne*, J.Swettenham, R. Cambell and M. Coleman. Dept. Hum.Comm.Sci, UCL, London, WC1 1PF, UK. Hierarchical figures (H.F.) have been used to demonstrate a “global advantage” in human perception. The literature is unclear as to whether individuals with autism also have a global advantage or whether they show more locally biased H.F. processing. Psychophysical data suggests that global advantage in this task is underpinned by the magnocellular visual system. We tested the

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hypothesis that H.F. processing is related to coherent motion detection, which also relies on the magno system and has been reported to be reduced in autism. Using random dot kinematograms and hierarchical figures, we measured motion coherence thresholds and degree of global / local bias in a group of children with autism (N = 16, mean age = 10y 4 m) and a group of matched controls (N = 17, mean age = 10 y, 1 m). The children with autism showed no evidence of global advantage, despite a global advantage in the controls. No significant group differences were seen in motion detection, but there were significant correlations in both groups between degree of global or local bias in the H.F. task and coherent motion detection, suggesting that a relationship exists between motion detection and the global advantage. This research was funded by the E.S.R.C. and UCL graduate school scholarships awarded to the first author. S4.2.5 DO BOYS WITH ASPERGER SYNDROME HAVE A NARROWING OF ATTENTIONAL FOCUS? EVIDENCE FROM BOUNDARY EXTENSION. P. Mitchell, D. Ropar and P. Chapman. School of Psychology, University of Nottingham, UK. A recent study by Mann and Walker (2003) suggests that individuals with autistic disorders have a narrowing attentional focus and that this can explain a wide range of phenomena associated with perception and cognition in autism. To test this hypothesis, we presented a boundary extension task. Boys with Asperger syndrome (n=18) were shown 16 scenes on an LCD screen and after a delay they were shown these scenes once again but with a different level of zoom (i.e. either zoomed in or zoomed out). Participants were tasked with adjusting the level of zoom (using arrow keys) until it matched what they remembered. If individuals had a narrowing of attentional focus, then they should display “boundary restriction” (i.e. zooming in more closely than at the time of encoding. In fact, though, they showed a highly significant boundary extension, to a level that was identical to that of comparison participants (12.5%). This study offers no support for the suggestion of narrowing attentional focus in

autism, and so another explanation is needed for distinctive aspects of perception and cognition in autism. Mann, T.A. & Walker, P. (2003). Autism and a deficit in broadening the spread of visual attention. Journal of Child Psychology and Psychiatry, 44, 274-284. S4.2.6 FREQUENCY SELECTIVITY IN AUTISM AND ASPERGER'S SYNDROME. E.J. Weisblatt and J.I. Alcántara. Departments of Psychiatry and Experimental Psychology, University of Cambridge, Cambridge UK, CB2 2AH Individuals with autism and Asperger's syndrome commonly report difficulty in understanding speech in the presence of background noise. Alcántara et al. (2003) found that the speech-in-noise perception abilities of high-functioning individuals with autism (HFA) or Asperger’s syndrome (AS) were significantly poorer than those of age-/IQ-matched controls, especially for background sounds that contained temporal and spectral dips. We hypothesised that abnormal low-level auditory processing, such as reduced frequency selectivity, might be responsible. In a follow-up study, the frequency selectivity abilities of 8 normal-hearing individuals with HFA/AS were measured and found to be abnormal at one centre frequency (Plaisted et al., 2003). To further investigate the role of frequency selectivity, we measured auditory filter bandwidths in 15 individuals with HFA/AS and 6 controls, at four centre frequencies. Listeners were required to detect a signal with a frequency of 500, 1000, 2000, or 4000 Hz, in the presence of a noise masker with a constant level, but whose spectrum contained a notch centred at the signal frequency. The threshold of the signal was determined for a series of notch widths. The function relating signal threshold and notch width was used to calculate the equivalent rectangular bandwidth (ERB), which is a measure of frequency selectivity (Moore et al 1986). The mean ERBs of the HFA/AS individuals were not significantly different from the controls for the centre frequencies measured. We conclude that HFA/AS individuals show frequency selectivity abilities that are within the normal range.

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Slide Session 4: Topic 3: Genetics IV S4.3.1 ALTERATION OF IMPRINTED GENE EXPRESSION IN RETT SYNDROME AND IN THE Mecp2-KNOCKOUT MOUSE . L.B.K. Herzing 1* and D.H. Ledbetter 2. 1Dept of Pediatrics, Northwestern University, Chicago IL 606141. 2Dept of Human Genetics, Emory University, Atlanta GA 303222. Mutations in the Rett syndrome (RS) gene MeCP2 have been identified in several patients with Angelman syndrome (AS) and autism, highlighting the phenotypic overlap between these disorders. UBE3A, the AS gene, and ATP10C are maternally expressed imprinted genes regulated by the AS-imprinting center (IC) that map to 15q11-q13, a strong autism gene candidate region. We have previously demonstrated that preferential loss of maternal ATP10C expression is coordinate with a gain of maternal ATP10C antisense expression in cell lines with AS-IC or MeCP2 mutations. Biallelic antisense transcription is also observed in cerebral tissue from male patients with MeCP2 mutations, and real-time RT-PCR analysis of total cortex from both male and female RS patients suggests that overall UBE3A expression levels are decreased compared with matched controls. Using a Mecp2-knockout mouse model of RS, we have preliminary evidence that Atp10c expression is imprinted in mouse cortex, and that loss of Mecp2 is again coordinate with a decrease in the expression of the maternal Atp10c allele. This change in expression appears to occur as early as the juvenile period, prior to overt phenotype expression. Work is ongoing to further characterize and quantitate imprinted expression during neuronal development and maturation. Together, our results suggest that MeCP2 mediates control of gene expression by the AS-IC, and that a decrease in expression of these genes may contribute to the phenotypic overlap between RS, AS and autism. Sponsored by the NIH, CAN and the IRSA.

S4.3.2 EPIGENETIC ALTERATION OF ANGELMAN SYNDROME GENE IN AUTISM BRAINS. Y-H. Jiang, Q. Liu and A.L. Beaudet. Dept. of Molecular & Human Genetics. Baylor College of Medicine. Houston TX 77030 Numerous cytogenetic studies have indicated that chromosome 15q11-q13 and genomic imprinting may play an important role in genetic etiology of autism. Maternal inheritance of either interstitial duplication of 15q11-q13 or isodicentric chromosome 15 are the two most common cytogenic abnormalities found in autism patients. Two disorders of genomic imprinting, Prader-Willi syndrome (PWS) and Angelman syndrome (AS), involve abnormalities of15q11-q13 region. The maternal deficiency of chromosome 15q11-q13 and mutation in UBE3A, a brain specific and maternally expressed ubiquitin protein ligase, are the major causes for AS. There are significant overlapping clinical features between AS and autism. We tested a hypothesis that UBE3A is a candidate gene from 15q11-q13 and epigenetic alteration of UBE3A contributes to the autism susceptibility. We have analyzed DNA methylation of CpG islands at the 5 of SNRPN and UBE3A, as well as a newly identified tissue-specific DNA methylation site at the 3 UBE3A from autopsy brain tissues and cell lines of autism patients. We have identified an abnormal DNA methylation at the 5 CpG of UBE3A in possible 2 out of 17 brain tissues. The 5 CpG of UBE3A is completely unmethylated in 60 normal controls but become partially methylated in two autism brains. We also found significantly reduction of UBE3A protein in 7 out 17 autism brain tissues by Western blot analysis. Searching of sequence alteration in CpG island/promoter region of UBE3A in autism patients is in process. The available data support that dysregulation of UBE3A expression in brains may contribute to the autism susceptibility and epigenetic alterations may play a major role in autism etiology. S4.3.3 MECP2 EXPRESSION IN POSTNATAL BRAIN IS AFFECTED BY CELL EXTRINSIC FACTORS. J.M. LaSalle, D. Braunschweig, T. Simcox and R.C. Samaco. Med Micro and Immuno,

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Rowe Program in Hum. Genet, UCD, Davis, CA, 95616 Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in females caused by mutation in MECP2 on Xq28. Similar to autism, onset of symptoms are delayed until 6-18 months of age, corresponding to a dynamic developmental expression of MeCP2 in the postnatal brain. Because of X chromosome inactivation (XCI), cells within RTT females are mosaic for expression of the MECP2 mutation. Using the Mecp2-null mouse model, we investigated the effect of Mecp2 mutation on XCI and developmental MeCP2 expression in wild-type (wt) expressing neurons by quantitative laser scanning cytometry. Mecp2-/+ female mice exhibited random regional distribution of Mecp2 mutant-expressing cells in brain, but a nonrandom distortion of XCI in the population, favoring expression of the Mecp2 wt allele. Interestingly, MeCP2 expression in Mecp2 wt-expressing cells from Mecp2-/+ mice was significantly lower than those from Mecp2+/+ age-matched controls. The negative effect of Mecp2 mutation on wt Mecp2 expression correlated with the percentage of Mecp2 mutant-expressing cells in the cortical tissue. Similar results were observed in two RTT females with identical MECP2 mutations. These results demonstrate that Mecp2-mutant neurons affect the development of surrounding neurons in a non-cell-autonomous manner and suggest that environmental influences may affect the level of MeCP2 expression in wild-type neurons. These results have important implications for designing therapies in female RTT patients and suggest that MeCP2 expression defects observed in autism may be caused by a combination of genetic and environmental factors. Supported by NIH/NICHD and the UC Davis M.I.N.D. Institute. S4.3.4 MECP2 EXPRESSION DEFECTS IN THE CEREBRAL CORTEX OF AUTISM PATIENTS MAY BE A RESULT OF BOTH TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS . R.P. Nagarajan, R.C. Samaco, D. Braunschweig and J.M. LaSalle*. Medical Microbiology & Immunology, UC Davis Sch. Med., Davis, CA 95616

Mutations in the X-linked gene MECP2 cause most cases of Rett syndrome, a neurodevelopmental disorder phenotypically similar to autism. MeCP2 is expressed ubiquitously but is developmentally regulated in the CNS, exhibiting high expression in a subset of mature neurons (MeCP2hi). We performed immunofluorescence and fluorescent in situ hybridization with riboprobes to analyze MeCP2 protein and mRNA levels in individual neurons by the novel approach of laser scanning cytometry. We constructed a tissue microarray of postmortem cerebral cortex samples from normal, autistic, Rett syndrome, and other patients. We found that the normal developmental increase in MeCP2 expression occurs at the transcriptional level in individual neurons leading to the switch to the MeCP2hi phenotype. All four autism samples exhibited defects in MeCP2 protein expression, apparently by different transcriptional and posttranscriptional mechanisms. These results suggest that different pathways controlling MeCP2 expression may be involved in the etiology of autism and Rett syndrome. Current studies include the construction and analysis of a new tissue microarray containing additional autism, Rett, and Down’s syndrome cerebral cortex and fusiform gyrus samples. These results are expected to further our understanding of pathways regulating the dynamic expression of MeCP2 in the postnatal brain and may help to determine the role of MeCP2 in autism and other neurodevelopmental disorders. Supported by the U.C. Davis M.I.N.D. Institute. S4.3.5 AUTISM IN ANGELMAN SYNDROME: IMPLICATIONS FOR AUTISM RESEARCH. S.U. Peters, A.L. Beaudet*, N.S. Madduri and C.A. Bacino. Depts. of Pediatrics & Mol. & Human Genetics, Baylor College of Medicine, Houston, TX 77030 Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, ataxia, and a happy/sociable disposition. Expression of the UBE3A gene from the maternal copy of chromosome 15 is essential to prevent AS. Maternally, but not paternally derived defects, such as duplications, within the AS critical region result in autistic symptomatology, suggesting the UBE3A

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gene might be implicated in the causation of autism. This study examined the prevalence of autism in AS in 19 children representing three known molecular classes of AS. Children were studied over the course of 1 year. 42% of this population, eight of 19 children, met criteria for autism according to the Autism Diagnostic Observation Schedule. Parents of children who were diagnosed with autism according to DSM-IV criteria as well as the ADOS-G were administered the Autism Diagnostic Interview - Revised. Data from the ADI-R were convergent with data from the ADOS-G in all cases. Children with co-morbid autism and AS scored lower on measures of language, adaptive behavior, and cognitive functioning, and demonstrated a slower rate of improvement over the course of the study. Further, they demonstrated deficits in communication and socialization that mirror those observed in children with idiopathic autism. The study highlights the phenotypic overlap between autism and AS and increases the probability that dysregulation of UBE3A may play a role in the causation of autism. Implications for the utility of the ADOS and the ADI-R in distinguishing autism in populations of children with severe to profound mental retardation will be discussed. S4.3.6 MOLECULAR CHARACTERIZATION OF 15Q11-Q13 DUPLICATIONS INVOLVED IN AUTISM BY HIGH RESOLUTION COMPARATIVE GENOMIC HYBRIDIZATION MICROARRAY .N. Wang 1, D. Liu 1 and N. Schanen 2*. 1Dept Human Genetics UCLA, Los Angeles, CA 90095 and Nemours Biomedical Research, A.I. duPont Hospital for Children, Wilmington, DE 19803 Maternally derived duplication of the imprinted region of chromosome 15q11-q13 leads to a complex neurobehavioral phenotype that often includes autism, cognitive deficits, and seizures. These duplications are the most common cytogenetic abnormality associated with autism. Multiple repeat elements within chromosome 15q11-q13 mediate a variety of rearrangements including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes as well as the deletions that cause Prader Willi and

Angelman syndromes. In order to elucidate the molecular structure of these duplication chromosomes, we have designed a high-resolution array-CGH platform. The array contains 79 clones that form a gapped contig across the critical region on 15q11-q13, and 21 control clones from other autosomes and the sex chromosomes. We used this array to assess samples from a set of patients carrying well-characterized rearrangements of 15q11-q13. All array-CGH results agree with the previous data for size and location of breakpoints as determined by FISH, quantitative Southern blot, and genotyping, and allow accurate detection of dosage of the region ranging from 1-6 copies. In addition, the increased resolution of the array allows us to detect atypical rearrangements that are missed by standard techniques. These results indicate that array-CGH is a powerful technique to study rearrangements of 15q11-q13. Slide Session 4: Topic 4: Descriptive

Diagnostic S4.4.1 RELIABILITY AND VALIDITY OF THE PDD BEHAVIOR INVENTORY. I.L. Cohen. NYS Institute for Basic Research in DD. Staten Island, NY 10314. The PDD Behavior Inventory (PDDBI) is a behavior checklist filled out by caregivers or teachers to assist in diagnostic evaluation, treatment planning and assessing response to intervention for people suspected of having a Pervasive Developmental Disorder (ages 2 through 12 years). Both adaptive and maladaptive behaviors are assessed in the scale, making it useful for treatment studies in which decreases in maladaptive behaviors, and improvements in adaptive social and language skills relevant to PDD are expected. The inventory was found to have very good internal consistency. Inter-rater reliability was better for adaptive behaviors than for maladaptive behaviors. Raw scores for adaptive skills increased with age of the child in the parent and teacher versions, as did measures of social pragmatic problems and semantic/pragmatic problems. Criterion-related validity with the Childhood Autism Rating Scale, the

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ADOS-G and the ADI-R - was high and the PDDBI had good sensitivity and specificity. Selected scales from the PDDBI correlated well with comparable factors of the Nisonger Child Behavior Rating Form, the Griffiths Mental Development Scales and the Vineland Adaptive Behavior Scales. Changes in PDDBI scores over time were also correlated with changes in these same measures. It was concluded that the PDDBI is both reliable and valid and is useful in providing information not typically available in most instruments used to assess children with PDD. S4.4.2 ARE PERSONS WITH AUTISM SPECTRUM DISORDERS AT RISK FOR THE DEVELOPMENT OF SEXUAL PROBLEMS? H. Hellemans. University of Antwerp, Belgium. From a theoretical viewpoint, the social and communicative deficits, the repetitive patterns and the neurobiological/cognitive disturbances of ASD, could be expected sometimes to result in the development of inappropriate or deviant sexual behavior. Most of the few studies on sexual behavior in people with ASD, have indeed reported inappropriate behavior e.g. masturbation in public. Several studies have found the use of objects in masturbation. Case studies have been published of DSM-IV-Sexual and Gender Identity Disorders in persons with ASD and of sexual offence in persons with Asperger’s Disorder. In a group of 24 institutionalized male persons with ASD and (borderline-)normal intelligence we found masturbation in public in 13%, hypermasturbation in 8%, masturbation with the use of idiosyncratic objects in 8% and inappropriate touching in 17%. One person met the DSM-IV-criteria of pedophilia and one of fetishism. Another person had pedophilic interests without meeting DSM-IV-criteria. Two persons were taking psychotropic drugs because of sexual problems. In a group of 20 institutionalized male persons with autistic disorder and mild mental retardation we found masturbation in public in 10 % and inappropriate touching in 10%. One person met the DSM-IV-criteria of pedophilia and one had a paraphilia-NOS. The sexual problems of two persons were treated with psychotropic drugs.

In summary, the literature and our own research suggest that inappropriate behavior occurs quite often in persons with ASD and that some persons with ASD have a paraphilia. However, no research exists about the frequency of inappropriate and deviant behavior in comparison with controls. More research is needed on this important issue. S4.4.3 THE DEVELOPMENT AND APPLICATION OF THE COGNITIVE AND SOCIAL PLAY ASSESSMENT SCALE FOR USE WITH CHILDREN WITH AUTISM. A. Sorman, K. White and C. Claflin*. Northwest Missouri State University, Maryville, MO 64468. Play has a vital role in children’s development. Because autistic children lack the skills to perform age appropriate play, there is a need for intervention and assessment, which is possible with the Cognitive and Social Play Assessment Scale. The scale was adapted from Wolfberg and Schuler (1993) and Westby (1980, 1991). Cognitive play categories are no interaction, observing, physical contact with toy, manipulation, functional/autosymbolic play, and symbolic/pretend play. Social play categories are isolation, orientation, parallel/proximity, and common focus. Additional information consists of time of day, people and number present, and location, and use of sensory motor toys/tools. Data used for the interrater reliability was randomly selected from videotape of an intensive intervention with an autistic preschooler. Interrater reliability was good with Cohen’s kappa scores for three trained raters ranging from .6768 - 82. This scale was found a reliable instrument to track developmental progress. Results of pilot data assessing longitudinal play development in response to the child-centered, Developmental, Individual Relationship-based Approach (Greenspan &Weider, 1998, 1999; Clinical Practice Guidelines, Interdisciplinary Council on Developmental and Learning Disorders, 2000) to early intervention will be presented. Sources of funding for this research include grants from Northwest Missouri State University, Applied Research Grants # 122424 & # 122160 to the principal investigator, and College of Education and

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Human Services Undergraduate Research Grants to student researchers. S4.4.4 SEVERE CHALLENGING BEHAVIOR IN INDIVIDUALS WITH AUTISM AND MENTAL RETARDATION: THE EFFECTS OF AN INTENSIVE CARE SYSTEM I.A. Van Berckelaer-Onnes and Y.M. Dijkxhoorn, Leiden University, The Netherlands. This study concerns the evaluation of two Very Intensive Care (VIC) units in two different institutions in The Netherlands over a period of three years. The units were evaluated at the three following levels: the client, the treatment, and the organisation. At the level of the client, different instruments were used concerning the developmental level / IQ, adaptive level, and maladaptive functioning. To acquire insight into the treatment and the organisation, analyses of the files and interviews with the caretakers and involved psychologists were done following the classification system of Singh (1997). In general, the daily living skills of the majority of clients improved, while their challenging behavior decreased. However, unit II proved to be more successful in decreasing challenging behavior. Analyses at the levels of treatment and organisation yielded an interesting difference between the two units. Although in both units treatment mainly focused on the prevention and correction of challenging behavior, unit II was slightly more directed on teaching new skills. On the basis of these results, we plead for a more developmental-oriented approach to challenging behavior. Enhancement of communication skills, in particular, should be the focus of attention. Instead of structuring to control, caretakers should structure to offer more autonomy. S4.4.5 ANALYSIS OF SOCIALINITITATIVE POTENTIAL AS A PIVOTAL VARIABLE IN THE PROGNOSIS FOR CHILDREN WITH AUTISM. L.A. Vismara, R.L. Koegel*, and L.K. Koegel. Autism Research & Training Center, University of California, Santa Barbara, CA 93106-9490. The literature on child-initiations suggests that certain types of child-initiations may be associated

with favorable treatment outcomes for children with autism. The current study examined whether patterns in object-related versus social-related child-initiations in children with autism were associated with good prognoses. Pre-intervention measures of social versus object-approach initiations were examined to assess their association with type of treatment outcome. The results showed that, if at pre-intervention a child engaged in social-approach behaviors focused primarily on obtaining social reinforcement, as opposed to initiations exhibited primarily to obtain an object, the child attained a much more favorable treatment outcome. Further, the findings also suggested that a positive ratio of social-approach to object-approach initiations (referred to as social initiative potential) appeared to be related to the emergence of positive outcomes. Implications for parent training interventions are discussed in relation to the social communicative interaction style between child and caregiver in order to optimize opportunities for social-approach initiations. Slide Session 4: Topic 5: Microbiology and

Immunology of Autsim Spectrum Disorder

S4.5.1 INCREASED SPONTANEOUS TNFalpha AND DECREASED IL-10 PRODUCTION IN PERIPHERAL AND ILEAL LYMPHOCYTES IN AUTISTIC CHILDREN. P. Ashwood, A. Anthony and A.J. Wakefield*. Paediatric Gastroenterology, Royal Free Medical School, London, UK. Recent studies have reported immune aberrations in children with autistic spectrum disorder (ASD) including, increased mucosal lymphocytic infiltration and abnormal patterns of cytokine release. This study sought to characterise spontaneous cytokine production in peripheral and ileal lymphocytes of children with ASD and entero-colitis. Lymphocytes were isolated from peripheral blood and from both epithelial and lamina propria mucosal compartments. CD3+ lymphocytes which spontaneously produced intracellular TNFalpha, IL-

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10, IL-2, IL-4 and IFNg were detected by flow cytometry. Cytokine profiles from ASD children (n=15), typically developing and histologically normal controls (n=14), and children with Crohn’s disease (CD) (n=10), were compared. Significantly increased numbers of TNF positive peripheral lymphocytes were noted in ASD children compared with normal controls (22% v 4%, p<0.004) and reached similar levels to those in CD children. However, lymphocytes positive for the regulatory cytokine IL-10 were reduced in ASD children compared with CD (2% v 16%, p<0.03). Within the ileum, lamina propria TNF positive lymphocytes were increased in ASD children compared with non-inflamed but not CD controls (15% v 3%, p<0.01) whereas intracellular IL-10 was reduced (1% v 11%, p<0.04). A similar pattern of increased TNF and reduced IL-10 was seen in epithelial lymphocytes. In addition lamina propria IL-4 positive cells were more numerous in ASD children compared with both groups (p<0.007). This study demonstrates a significant elevation of TNF with a corresponding reduction in regulatory IL-10 in the ileum of children with ASD and entero-colitis. S4.5.2 STRAIN DIFFERENCES IN ONTOGENY OF CNS DISTURBANCES FOLLOWING LATE GESTATIONAL IMMUNE CHALLENGE IN A MOUSE MODEL. M. Hornig, R. Schlaberg, D. Chian, C. Kirk, P. Hardigan and W.I. Lipkin*. Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, New York, NY 10032. Pre- and postnatal exposures to a wide range of infectious agents have been implicated in autism and related disorders. Although injury may be partly determined by pathogen tropism and replicative strategies, host responses associated with infection provide a unifying thread with which to understand the spectrum of outcomes. One determinant of CNS sequelae following infection arises from maternal host responses to microbial challenge and subsequent effects on the developing fetus. Using an animal model of neurodevelopmental damage with general implications for late gestational infections, we administered a synthetic viral mimic (polyIC) to pregnant dams (GD16) of two mouse

strains differing in autoimmune disease sensitivity. Postpubertally, hyperactivity and impulsivity in open field testing were similar in offspring of polyIC-treated dams of both strains; however, earlier timepoints revealed divergent early locomotor development, open field exploration, and repetitive behaviors. Maternal cytokine and chemokine profiles also varied by strain. Furthermore, regional brain reelin and BDNF mRNA levels were altered in polyIC C57 offspring and correlated with behavior. Delineating gene x environment x timing interactions in this animal model may help to differentiate between the pathogenesis of neuropsychiatric disorders commonly presenting after puberty, such as schizophrenia, from those with early onset, such as autism. Supported by grants HD37546 (WIL) and MH01608 (MH), and The Ellison Medical Foundation (WIL). S4.5.3 FREQUENCY OF HISTOLOGIC ENTEROCOLITIS AND LYMPHONODULAR HYPERPLASIA IN AUTISTIC CHILDREN PRESENTING FOR ILEOCOLONOSCOPY. A.C. Krigsman, M. Boris and A. Goldblatt. New York Univ. Sch. of Med., New York, NY 10016. OBJECTIVE: Gastrointestinal symptoms occur with high frequency in children with autistic spectrum disorder (ASD). Histologic mucosal abnormalities seen upon standard light microscopy have been reported in over 65% of symptomatic ASD children who underwent ileocolonoscopy, but this finding has not been independently corroborated. This study seeks to determine the frequency of such histologic changes in our patient group. METHODS: The pathology records of 146 ASD children who underwent ileocolonoscopy were reviewed. Indications included chronic diarrhea, constipation, abdominal pain, and abdominal distension. Initial pathologic review was performed by 5 separate institutional pathologists who were unaware of the underlying ASD diagnosis. Data regarding the type (lymphocytic, neutrophilic, and eosinophilic) of inflammation, location, and presence of pathologic lymphonodular hyperplasia (LNH) were extracted. RESULTS: In the ileum, LNH was observed in 94 of 130 patients (72%). Ileitis was noted in 46 of 139 patients (36%). In the colon, 100 of 145 (69%)

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patients exhibited one or multiple forms of mucosal inflammation. Of these, the majority (51%) harbored the pathology in at least 4 distinct anatomic areas with 64% showing this pathology in at least 3 areas. The involved areas were not contiguous and no particular anatomic location predominated. CONCLUSIONS: Enterocolitis is a common finding in ASD children presenting with chronic gastrointestinal symptoms. Therapy aimed at reducing the degree of inflammation may offer significant symptomatic relief and improvement in their general wellbeing and quality of life. S4.5.4 THE ROLE OF MATERNAL IMMUNITY IN SUSCEPTIBILITY TO VIRUS INFECTION AND DISEASE. G.F. Rall, J. Chandra, L.A. Gechman and C.E. Patterson. The Fox Chase Cancer Center, Philadelphia, PA 19111. What role the immune response plays in the etiology of autistic spectrum disorders (ASD) remains controversial. Current efforts to determine the basis of ASD have generally been restricted to the affected child, although it is apparent that the development of a child's immune response is strongly influenced by maternal immunity. To address the impact of maternal immunity on the response of newborns to viral infection, we have used a transgenic mouse model of measles virus (MV) infection in which a human MV receptor, CD46, is specifically targeted to CNS neurons using the neuronal promoter, neuron-specific enolase (NSE). Virus-challenged adult NSE-CD46+ mice mount a robust response that clears the infection and affords lifelong protection, whereas naïve CD46+ neonates cannot resolve the infection, despite a similar immune response induction. In contrast to naïve pups, newborns weaned on mothers recently exposed to MV were protected from CNS disease, likely due to the transplacental transfer of maternal antibodies. In contrast, pups weaned on mothers that were exposed to MV long before conception were not protected and showed no evidence of immune induction, suggesting that previous maternal exposure tolerized offspring to subsequent viral challenge. Interestingly, this process seems to be virus-specific, as challenge with another murine pathogen, LCMV, did not result in tolerance. These

data indicate that the maternal immune response can dramatically affect the outcome of a subsequent challenge in her offspring, leading to either protection or enhanced susceptibility, depending on exposure history. Supported provided from the M.I.N.D. Institute and NIH grant NS40500. S4.5.5 TAGMAN RT-PCR DETECTION OF MEASLES VIRUS GENOMIC RNA IN CEREBROSPINAL FLUID IN CHILDREN WITH REGRESSIVE AUTISM. O. Sheils, J.J. Bradstreet, J. El Dahr, S.M. Montgomery, A.J. Wakefield, J.J. O’Leary. Department of Histopathology ST James' Hospital Dublin Ireland In light of encephalopathy, presenting in children as autistic regression closely following MMR vaccination, affected (ASD) children (n = 28) underwent lumbar puncture and examination of cerebrospinal fluid (CSF) for measles virus (MV) genomic RNA. Presence of MV Fusion (F) gene was examined by TaqMan RT-PCR. Control CSF samples (n = 37) were obtained from children in remission from leukaemia (n = 20), children undergoing shunt insertion for hydrocephalus (n = 3) and young adults with either multiple sclerosis (n = 7) or encephalitis (n = 7). All ASD cases and pediatric controls had received MMR vaccine. MV haemaglutinnin (H) gene allelic discrimination (AD) assay was performed on cases where adequate MV amplicon was obtained. MV F-gene was present in CSF from 19 of 28 (68%) cases and in one of 37 (3%) controls (RR = 25.12; 3.57-176.48, p<0.00001). Where data were available on CSF (5 cases), AD assay confirmed that the MV H-gene product was consistent with vaccine strain. The findings confirm a highly significant statistical association between the presence of MV RNA in CSF and autistic regression following MMR vaccination.

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S4.5.6 REDUCED IG RESPONSE TO COMMON VACCINE ANTIGENS FOR PATIENTS WITH AUTISM SPECTRUM DISORDER. J. Van de Water*, P. Ashwood, R. Hansen, B. Goodlin-Jones, K. Lam and M.E. Gershwin. Internal Medicine and M.I.N.D. Institute, UC Davis, Davis, CA 95616 There is a growing awareness of an immunological involvement in some ASD children. To better define the immune status of children with ASD, we examined by ELISA the serologic response of patients and age-matched typically developing (TD) controls to common vaccine antigens. These included Bordetella, Diptheria, Tetanus, Measles, Mumps and Rubella. All children analyzed were vaccinated with DTaP and MMR. Based on vaccination schedules, comparisons were made between patients and controls in three age groups: 2-5 yrs, 5-8 yrs and 8-14 yrs. The most striking differences were observed in the 2-5 age group where patients with ASD had a significantly lower IgG response to Bordetella (p d 0.0003), Diptheria (p d 0.006), and Mumps (p d 0.043) than TD controls. There was also a trend for a lower IgG responses against Measles and Tetanus in the ASD group. In the 5-8 age group, there were no differences in the response to any of the test antigens. In the over 8 age group, while there was a trend towards lower IgG responses to Bordetella, Tetanus and Mumps antigens, only the IgG response to Measles was significantly reduced (p d 0.016). Interestingly, the response to Rubella was equal in groups over time. Finally, at no time point did the median of the response of the ASD group exceed that of the TD population. In conclusion, all patients with ASD were immunopositive for the vaccine antigens tested, their responses were significantly lower than the TD controls suggesting an immune dysregulation in these children.

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Author Index

175

A

Abdullah, M 18, 25, 69, 102 Abramson, R 19, 21, 23, 28, 33, 36,

72, 80, 84, 90, 116, 130, 146

Adams, J 19, 33, 75, 76, 131 ADDM CADDRE 24, 97 AGRE Consortium 19, 32, 72, 126 Aharon, I 27, 36, 108, 146 Akshoomoff, N 26, 105 Alarcón, M 19, 72 Alcántara, J 41, 166 Alekseyenko, O 22, 86 Alexander, A 14, 27, 48, 51, 108 Allen, S 15, 17, 53, 64, 65 Amaral, D 24, 25, 98, 101 Amini, E 15, 56 Anderson, D 17, 39, 63, 157, 158 Anderson, G 19, 21, 74, 81 Anderson, M 23, 93 Anthony, A 42, 171 Antrop, I 37, 149 Antzoulatos, E 38, 153 Arguin, M 14, 51 Arndt, T 38, 155 Arnold, J 36, 145 Arnstein, L 39, 156 Aschner, J 29, 119 Aschner, M 29, 119 Ashley-Koch, A 21, 27, 83, 111 Ashton, K 15, 56 Ashwin, C 13, 26, 45, 107 Ashwood, P 42, 171, 174 Audhya, T 19, 74 Autism Spectrum Disorders Canadian-American Research Consortium

21, 82, 36, 143

Avramopoulos, D 23, 89 Awad, M 15, 56 Aylward, E 31, 121

B

Bachevalier, J 31, 125 Bacino, C 41, 168 Baeyens, D 37, 149 Bailey, A 38, 151 Baio, J 24, 96 Baird, G 23, 27, 29, 91, 110,

117 Bakardjiev, A 33, 131 Baranek, G 35, 142 Barker, L 14, 49 Barlow, C 29, 118 Baron, C 21, 82 Baron-Cohen, S 13, 18, 26, 32, 34, 40,

45, 67, 107, 128, 133, 162

Barton, M 15, 17, 53, 64, 65 Barua, M 19, 73 Bauman, M 38, 152, 153 Bauminger, N 40, 162 Baxter, M 34, 135 Bay, R 17, 66 Bean, J 34, 137 Beaudet, A 22, 41, 86, 88, 167,

168 Bebko, J 36, 144 Beck, C 23, 93 Bedard, A 20, 77 Behen, M 13, 46 Bejoian, L 15, 56 Bellinger, D 20, 78 Belmonte, M 13,18, 45, 67 Belzince, M 28, 42, 115, 174 Bennetto, L 36, 37, 145, 148 Bernier, R 13, 31, 47, 121, 122 Berringer, D 27, 109 Berthiaume, C 14, 41, 51, 165 Bespalova, I 19, 72 Beversdorf, D 16, 61 Bigler, E 14, 20, 25, 48, 49, 76,

101 Bishop, D 32, 126 Bishop, S 39, 158 Black, D 17, 36, 64, 145 Blades, M 14, 51 Blatt, G 38, 152, 153

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Author Index

176

Blevins, C 39, 157 Bloch, J 40, 160 Bloomquist, M 31, 121 Bloss, C 18, 26, 68, 105 Boeschoten, M 13, 47 Bölte, S 31, 39, 122, 158 Bomba, M 16, 36, 57, 144 Boner, M 15, 55, 42, 172 Bonnel, A 21, 81 Boorstein, H 15, 17, 53, 64, 65 Boser, K 18, 41, 69, 165 Bowler, D 13, 18, 36, 43, 70, 71,

146 Boyle, C 20, 78 Bradley, A 22, 86 Bradstreet, J 42, 173 Braithwaite, M 28, 114 Braunschweig, D 22, 38, 41, 87, 89, 155,

167, 168 Breitenbach, M 20, 77 Brewster, A 17, 62 Brian, J 16, 28, 33, 34, 61, 113,

132, 133 Brimacombe, M 18, 22, 23, 24, 67, 85,

90, 91, 98 Brown, R 39, 156 Brown, T 21, 83 Bryson, S 28, 33, 34, 113, 132,

133 Bui, Q 34, 134 Buitelaar, J 15, 18, 23, 54, 68, 69,

91 Buonocore, M 24, 25, 98, 101 Burack, J 26, 27, 31, 105, 109,

124 Burnette, C 13, 39, 43, 159 Burt, R 40, 164 Buxbaum, J 19, 72 Buysse, A 40, 164

C

Campbell, R 41, 165 Cantor, R 19, 32, 72, 126 Cao, J 24, 94 Caplan, R 16, 59 Carlson, C 39, 157 Carter, A 17, 28, 42, 65, 114,

115, 174

Carter, E 29, 117 Casida, J 29, 118 Cauich, C 13, 45 Caviness Jr, V 25, 33, 100, 131 Chabris, C 27, 36, 108, 146 Chandana, S 13, 46 Chandler, S 23, 27, 91, 110 Chandra, J 42, 173 Chapman, P 41, 166 Charak, D 39, 159 Charles, J 39, 156 Charman, T 23, 27, 29, 91, 110,

117 Chawarska, K 28, 115 Chen, G 32, 126 Chian, D 42, 172 Chiang, C 35, 138, 140 Choate, P 23, 93 Christ, L 22, 88 Chu, J 16, 61 Chudley, A 20, 77 Chugani, D 13, 46 Chugani, H 13, 46 Chung, K 25, 103 Cicchetti, D 16, 58 Claflin, C 25, 39, 42, 102, 157,

170 Clark, J 27, 36, 108, 146 Coates, H 40, 164 Cohen, I 42, 169 Cohen, S 26, 107 Coleman, M 14, 41, 49, 165 Collaborative Programs for Excellence in Autism

15, 37, 54, 55, 149

Collins, E 35, 142 Condouris, K 27, 109, 110 Connolly, C 26, 27, 106, 109 Conroy, J 21, 81 Constantino, J 32, 127 Coo, H 20, 77 Cook, E 16, 21, 23, 58, 80, 81,

90 Coon, H 20, 37, 76, 148 Cooper, E 37, 147 Cope, H 28, 116 Corbett, B 18, 25, 69, 102 Corsello, C 17, 63 Courchesne, E 13, 18, 25, 33, 44, 68,

100, 130 Crais, E 35, 142

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Author Index

177

Creaghead, N 34, 137 Croen, L 20, 23, 24, 76, 93, 94,

97 Cuccaro, M 17, 19, 21, 22, 23, 27,

28, 33, 63, 72, 80, 83, 84, 88, 90, 111, 112,

116, 130

D

D’Entremont, B 39, 157 D’Esposito, M 14, 52 Dahl, B 13, 32, 46, 125 Dalton, K 14, 27, 48, 51, 108 Daniels, M 22, 23, 85, 90 Dapretto, M 16, 59 David, A 24, 42, 172 Davidson, R 14, 27, 48, 51, 52, 108 Davies, S 21, 84 Davis, N 28, 42, 114, 174 Dawson, G 13, 16, 31, 37, 47, 58,

121, 122, 148 Dawson, M 41, 165 De Clercq, A 40, 164 de Jonge, M 36, 37, 145, 147 Dean, A 38, 151 DeLorey, T 34, 136 Dementieva, Y 33, 130 den Boer, J 19, 74 Deruelle, C 31, 123 Desposito, F 23, 24, 91, 98 Desrocher, M 26, 105 DeStefano, F 20, 78 Deunk, M 15, 56 Deutsch, C 33, 131 DeVito, T 25, 100 Di Martino, A 16, 60 Diehl, J 36, 145 Dietz, C 23, 91 Dijamco, A 33, 34, 132, 136 Dijkxhoorn, Y 42, 171 Dinh, E 20, 76 Dissanayake, C 34, 134 Dixon, P 15, 17, 53, 64, 65 Dominick, K 25, 99 Donnelly, S 19, 21, 28, 33, 72, 84,

112, 116, 130 Dosman, C 16, 61 Drew, A 29, 117

Drewry, J 25, 103 Drmic, I 16, 61 Drost, D 25, 100, 42, 174 Dufek, S 15, 39, 52, 156 Dumont-Mathieu, T 15, 17, 53, 65 Dunn, M 16, 58 Duvall, J 21, 81 Dykstra, J 35, 142

E

Edgell, D 23, 92 Ehrman, K 26, 27, 106, 109, 110 El Dahr, J 42, 173 Enns, J 31, 124 Esser, E 15, 17, 53, 64, 65 Evancie, L 27, 110 Evans, B 17, 38, 64, 151 Evans, J 17, 38, 64, 151

F

Faja, S 31, 121 Falb, M 23, 92 Fallin, M 23, 89 Feczko, E 27, 36, 108, 146 Fein, D 15, 17, 27, 53, 64, 66,

111 Feineis-Matthews, S 31, 122 Feldman, R 34, 133 Field, K 31, 121 Filipek, P 33, 131 Fillmore, P 31, 123 Finkelmeyer, A 14, 49 Fitzgearld, M 21, 81 Flanagan, T 27, 109 Folstein, S 27, 112 Fombonne, É 21, 81 Frazier, J 25, 100 Freeman, S 15, 53 French, A 23, 93, 42, 172

G

Gabriels, R 17, 28, 39, 63, 116,

156, 159 Gaffrey, M 31, 123 Gage, N 31, 123

I M F A R

Author Index

178

Gaigg, S 13, 18, 36, 43, 70, 71, 146

Gallagher, L 21, 81 Gamliel, I 34, 133 Gardiner, J 18, 36, 70, 71, 146 Gariépy, D 21, 81 Gauthier, J 21, 81 Gechman, L 42, 173 Gelman, N 25, 100 Germine, L 14, 52 Gernsbacher, M 14, 27, 32, 48, 51, 108,

127 Gershwin, M 42, 174 Geschwind, D 19, 21, 32, 37, 72, 81,

83, 126, 150 Geurts, H 37, 149 Giarelli, E 15, 25, 40, 42, 54, 102,

160, 174 Gibbs, M 17, 36, 64, 145 Gilbert, J 19, 21, 22, 27, 28, 72,

83, 84, 88, 111, 112 Gill, M 21, 81 Gilliam, T 21, 32, 83, 126 Gilotty, L 17, 36, 64, 145 Gitcho, N 37, 150 Gleeson, K 14, 49 Goin, R 39, 159 Golan, O 32, 128 Goldberg, J 31, 124 Goldfarb, M 18, 67 Goldsmith, H 14, 27, 32, 48, 51, 108,

127, 128 Goldstein, G 18, 70, 71 Gómez, J 40, 163 Gomot, M 13, 45 Goodlin-Jones, B 24, 25, 32, 42, 98, 101,

129, 174 Gordon, B 15, 55, 56 Gratier, M 33, 132 Green, J 15, 17, 53, 64, 65 Gregg, J 21, 22, 82, 85 Grether, J 20, 23, 24, 76, 79, 93,

97 Grimme, A 31, 121 Grindell, V 26, 105 Gross-Tsur, V 40, 160 Grubber, J 28, 112 Gurney, J 23, 92 Gutstein, S 32, 128

H

Haarmann, H 18, 69 Hadjikhani, N 27, 36, 108, 146 Hagerman, P 22, 85 Hagerman, R 22, 26, 85, 107 Hahn, L 27, 111 Haines, J 27, 112 Haist, F 31, 123 Hall, A 21, 23, 28, 36, 80, 90,

116, 146 Halladay, A 34, 135 Hallmayer, J 14, 32, 50, 126 Hamstra, J 24, 25, 98, 101 Hansen, R 23, 24, 42, 93, 94, 97,

174 Hardan, A 18, 24, 68, 98 Hardigan, P 42, 172 Harford, M 16, 61 Harley, A 23, 93 Harpur, J 15, 56 Harris, G 25, 27, 36, 99, 100,

108, 146 Hasegawa, T 26, 35, 107, 142 Hashemi, E 34, 136 Hellemans, H 42, 170 Hendry, J 25, 100 Henry, M 13, 43 Hepburn, S 28, 35, 116, 140 Herbert, M 33, 131 Hertz-Picciotto, I 23, 93, 94 Herzing, L 41, 167 Hessl, D 26, 108 Hill, D 17, 39, 63, 156, 159 Hill, W 32, 126 Hillier, A 16, 61 Hobson, P 40, 162, 163 Hodge, S 25, 100 Hodgson, J 33, 131 Hogart, A 22, 87 Holden, J 20, 21, 77, 82 Hooker, C 14, 52 Hopkins, B 23, 93 Hornig, M 42, 172 Hsu, W 15, 54 Hudry, K 35, 138 Huff, R 23, 93 Huggins, R 34, 134 Hughes, G 23, 93

I M F A R

Author Index

179

Hulshoff Pol, H 25, 99 Hume, K 26, 104 Hunyadi, E 13, 45 Huo, Y 23, 89 Hutsler, J 38, 154 Hyman, S 16, 58

I

Iarocci, G 31, 124 Ingersoll, B 28, 113 Ingram, J 38, 155 Isenberg, L 31, 123 Ittenbach, R 19, 24, 25, 42, 75, 94,

102, 174 Ivers, B 17, 39, 63, 156, 159 Iversen, P 21, 83

J

Jacquemont, S 22, 85 Jacques, S 26, 27, 105, 109 Jaworski, J 21, 27, 83, 84, 111 Jemel, B 14, 51 Jenner, W 39, 156 Jiang, Y-H 41, 167 Jobling, A 28, 114 Johnson, S 23, 40, 92, 164 Johnson, W 22, 85 Jones, W 28, 115 Joober, R 21, 81 Joseph, R 26, 27, 36, 37, 106,

108, 109, 146, 148 Juhasz, C 13, 46 Junaid, M 19, 22, 73, 86 Juska, J 15, 56 Just, M 37, 147

K

Kahn, R 25, 99 Kana, R 37, 147 Kanfi, E 35, 139 Karapurkar, T 20, 77, 78 Kasari, C 15, 53 Kearney, G 21, 81 Keen, D 28, 114 Kees, E 32, 127

Keller, T 37, 147 Kelley, E 27, 111 Kema, I 19, 74 Kemner, C 13, 25, 36, 37, 47, 99,

147 Kemnerand, C 145 Kemper, T 38, 152, 153 Kenemans, J 13, 47 Kennedy, DN 25, 33, 100, 131 Kennedy, DP 13, 44 Kenworthy, L 17, 36, 64, 145 Kerchner, K 39, 157 Keshavan, M 18, 24, 68, 98 Killiany, R 25, 99 Kim, K 29, 119 King, L 39, 156 Kirk, C 42, 172 Kitzmiller, J 16, 61 Kleinhans, N 31, 123 Kleinman, J 15, 17, 53, 64, 65 Klin, A 16, 28, 37, 58, 115,

148 Knight, R 14, 52 Knobel, M 18, 41, 69, 165 Koegel, L 42, 171 Koegel, R 42, 171 Konidari, A 19, 72 Kono, N 32, 126 Konstantareas, M 37, 147 Kopelioff, L 14, 50 Koul, O 17, 38, 64, 151 Kowal, D 19, 22, 73, 86 Kuhn, J 17, 28, 42, 65, 114,

115, 174 Kunihira, Y 26, 35, 107, 142 Kuroda, Y-I 38, 154 Kuschner, E 37, 148

L

Lacasse, H 21, 81 Lacerda, A 18, 68 Ladd, B 34, 135 Lahaie, A 14, 51 Lainhart, J 14, 20, 25, 48, 49, 76,

101 Lajonchere, C 21, 37, 83, 150 Lam, K 42, 174 Lambert, G 22, 85

I M F A R

Author Index

180

Lamendola, M 23, 90 Lammers, C 24, 25, 98, 101 Lampard, R 23, 92 Landa, R 34, 134 Landry, O 26, 27, 105, 109 Lanz, S 15, 17, 53, 65 Larochelle, S 37, 150 LaSalle, J 20, 22, 38, 41, 80, 87,

89, 155, 167, 168 Latz, J 27, 111 Lauder, J 29, 118 Lawlor, M 15, 56 Lawson, J 40, 162 Ledbetter, D 21, 41, 81, 167 Lee, J 14, 49 Lee, L-C 21, 24, 84, 95 Lee, N 24 Lee, P 17, 36, 64, 145 Lee, T 40, 162 Leffell, S 21, 84 Levine, S 18, 69 Levy, S 15, 19, 24, 40, 54, 75,

160 Lewis, J 33, 130 Li, H 19, 73 Li, L 22, 85 Lipkin, W 42, 172 Liu, D 41, 169 Liu, Q 41, 167 Loesch, D 34, 134 Logan, W 16, 36, 57, 144 Lombardo, M 15, 56 López-Hurtado, E 38, 153 Lord, C 15, 16, 17, 24, 35, 36,

37, 39, 54, 58, 63, 96, 117, 138, 143, 149,

157, 158 Loth, E 40, 163 Loucas, T 23, 27, 91, 110 Loveland, K 17, 31, 62, 125 Luna, B 37, 151 Lutgring, J 40, 164 Luthert, P 38, 151 Luyster, R 15, 37, 54, 149

M

Ma, D 21, 84 Madduri, N 41, 168

Makris, N 25, 33, 100, 131 Maley, A 32, 126 Mandell, D 24, 94 Manning-Courtney, P 21, 34, 84, 137 Manteuffel, B 24, 94 Marshia, G 15, 17, 53, 64, 65 Martchek, M 38, 152 Martin, C 21, 81, 83 Martin, E 27, 111 Mastergeorge, A 15, 56 Mateeva, O 34, 136 Matteson, K 21, 84 Matthews, T 25, 103 Maybery, M 32, 126 Mays, L 31, 123 McCauley, J 27, 111, 112 McDermott, C 33, 38, 34, 132, 133,

151 McGee, G 24, 96 McGrath, L 16, 25, 27, 36, 58, 100,

108, 146 McIntosh, D 14, 48 McMahon, C 35, 141 McMahon, W 14, 16, 20, 25, 37, 48,

49, 58, 76, 101, 148 Meally, E 21, 81 Megson, M 19, 75 Mei, H 27, 111 Meinzen-Derr, J 24, 36, 96, 143 Melmed, R 17, 66 Meltzoff, A 16, 58 Mendoza, S 18, 69 Menold, M 21, 27, 84, 111 Merriman, B 32, 126 Mesibov, G 35, 140 Mesibov, M 35, Meyer, J 40, 162, 163 Mikaelian, B 13, 43 Miller, R 16, 61 Milliken, D 21, 82 Milne, E 41, 165 Minderaa, R 19, 74 Ming, X 22, 23, 85, 90 Minshew, N 16, 18, 24, 37, 58, 59,

68, 70, 71, 98, 147, 148, 151

Mitchell, P 16, 41, 57, 166 Mizuno, A 13, 32, 46, 125, 36,

143 Moldofsky, H 16, 61

I M F A R

Author Index

181

Molloy, C 21, 36, 84, 143 Momoi, M 19, 22, 73, 86 Montgomery, S 42, 173 Moore, C 20, 77 Moore, J 27, 111 Morgan, A 39, 157 Mori, M 19, 73 Morrier, M 24, 96 Morrissey, J 17, 62 Morrow, A 21, 36, 84, 143, 36,

143 Mosconi, M 25, 103 Mottron, L 14, 21, 31, 37, 41, 51,

81, 124, 150, 165 Muddasani, S 24, 98 Mulder, E 19, 74 Müller, R-A 13, 31, 32, 45, 46, 123,

125 Mundy, P 13, 39, 43, 159 Munson, J 16, 37, 58, 148 Murphy, N 21, 81 Murphy, R 40, 164 Murray, D 34, 137, 36, 143 Muzik, O 13, 46 Myers, B 39, 159

N

Naber, F 15, 54 Nacewicz, B 14, 27, 48, 51, 108 Nagarajan, R 41, 168 Naigles, L 27, 111 Najafee, R 21, 81 Narita, M 33, 34, 131, 135 Narita, N 33, 34, 131, 136 Nelson, D 22, 86 Nelson, K 24, 97 Nelson, S 19, 21, 32, 72, 81, 126 Newschaffer, C 21, 23, 24, 84, 89, 92,

95 Nguon, K 34, 135 Nicholas, J 39, 156 Nicolson, R 16, 25, 61, 100 Nishijima, I 22, 86 Noens, I 17, 65 Noonan, A 20, 77 Nowicki, S 22, 85

O

O’Brien, L 33, 131 O’Grady, J 15, 56 O’Leary, J 42, 173 Odom, S 26, 104 Odouli, R 20, 24, 76, 97 Ogden, L 17, 39, 63, 156, 159 Olson, L 27, 112 Oosterlaan, J 37, 149 Oti, R 39, 157 Ouellette-Kuntz, H 20, 77 Owen, E 14, 52 Ozonoff, S 37, 148

P

PA-CADDRE 15, 19, 24, 25, 40, 42,

54, 75, 94, 103, 160, 161, 174

Palmen, S 25, 99 Palmer, R 24, 95 Panagiotidas, H 13, 47 Pandey, J 15, 17, 53, 64, 65 Pang, E 16, 36, 57, 144 Paparella, T 15, 53 Parikh, A 23, 90 Pascalis, O 14, 51 Patterson, C 42, 173 Patterson, P 29, 118 Paul, M 31, 121, 122 Pavlosky, W 25, 100 Paxton Jones, M 14, 49 Paylor, R 22, 86 Pearlman-Avnion, S 27, 110 Pearson, D 17, 31, 62, 125 Peddada, S 20, 80 Pennington, B 37, 148 Pepperberg, I 32, 129 Pericak-Vance, M 19, 21, 22, 27, 28, 72,

83, 84, 88, 111, 112, 116

Perra, O 13, 44 Perry, H 26, 107 Pessah, I 29, 119 Peters, S 41, 168 Piggot, J 14, 50 Pilowsky, T 34, 40, 133, 160 Pinto-Martin, J 15, 19, 24, 25, 40, 42,

I M F A R

Author Index

182

54, 75, 94, 103, 160, 161, 174

Poirier, M 13, 43 Ponnet, K 40, 164 Poston, V 35, 142 Poustka, F 31, 39, 122, 158, 36,

143 Prendeville, J 34, 137 Prieto, J 38, 153 Prosick, T 20, 77 Provencal, S 14, 25, 48, 49, 101 Pullara, O 15, 56 Pullarkat, P 19, 22, 73, 86 Pullarkat, R 19, 22, 73, 86 Pyles, D 24, 96

Q

Qiu, S 17, 39, 63, 158

R

Rabionet, R 19, 72 Radloff, G 21, 84 Rajakumar, N 25, 100 Rajendran, G 16, 57 Rall, G 42, 173 Ramji, N 20, 77 Ramloll, R 14, 49 Ramoz, N 19, 72 Randolph, B 31, 124 Rao, Y 22, 87 Rausch-Harris, D 15, 52 Ravan, S 21, 23, 28, 33, 36, 80,

90, 116, 130, 146 Ray, E 35, 142 Raymaekers, R 37, 149 Reavis, S 25, 35, 103, 140 Redcay, E 13, 25, 44, 100 Reed, C 14, 50 Reiss, A 14, 50 Reuhl, K 34, 135 Rhee, T 36, 144 Rice, C 24, 96 Richler, J 15, 37, 54, 149 Risi, S 15, 17, 35, 37, 39, 54,

63, 138, 149, 157, 158 Rivera, S 13, 43 Roberts, W 16, 28, 33, 34, 36, 57,

Robins, D 13, 15, 17, 45, 53, 64, 65

Rocha, M 39, 156 Rocke, D 22, 85 Rodger, S 16, 28, 58, 114 Rodier, P 38, 155 Rodriguez, V 18, 67 Roeyers, H 17, 26, 37, 40, 66, 106,

149, 164 Rogers, S 28, 35, 37, 40, 116,

140, 148, 162 Romdalvik, J 19, 33, 75, 131 Rondan, C 31, 123 Ropar, D 41, 166 Rothermel, R 13, 46 Rouleau, G 21, 81 Russo, N 27, 109 Rutherford, M 35, 140

S

Sahoo, T 22, 86, 88 Sajdel-Sulkowska, E 34, 135 Salimpoor, V 26, 105 Samaco, R 22, 38, 41, 87, 89, 155,

167, 168 Saulnier, C 16, 58 Saumier, D 14, 37, 51, 150 Schanen, N 41, 169 Schantz, S 20, 79 Schendel, D 20, 77 Schjolberg, S 15, 55 Schlaberg, R 42, 172 Schlottmann, A 35, 142 Schmidt, H 35, 138 Schnack, H 25, 99 Schreibman, L 15, 28, 33, 39, 52, 113,

129, 156 Schroer, R 22, 88 Schultz, R 13, 45 Schumann, C 24, 25, 98, 101 Schwartz, S 22, 88 Sebrechts, M 14, 49 Senju, A 26, 35, 107, 142 Sergeant, J 37, 149 Sgro, G 24, 94 Shalev, R 40, 160 Sharieff, W 16, 61

I M F A R

Author Index

183

Shaw, C 22, 86 Shear, P 34, 137 Sheils, O 42, 173 Sherman, D 32, 129 Shi, L 29, 118 Shinawi, M 22, 88 Shook, J 31, 122 Shulman, C 35, 139 Shumway, S 28, 117 Sigman, M 16, 23, 34, 35, 58, 59,

93, 133, 136, 141 Silbergeld, E 20, 78 Siller, M 35, 141 Silverman, J 19, 72 Simcox, T 22, 38, 41, 87, 155,

167 Simon, J 21, 81 Simonoff, E 23, 27, 91, 110 Skaar, D 22, 88 Slaughter, V 35, 138 Smith, J 16, 19, 61, 72 Smith, R 16, 61 Snyder, J 27, 108 Solomon, M 32, 40, 129, 162 Soong, W 35, 140 Sorman, A 42, 170 Souders, M 15, 19, 25, 40, 54, 75,

102, 160 Soulières, I 37, 41, 150, 165 Sparrow, S 16, 58 Spence, A 16, 31, 37, 58, 123,

148 Spence, S 21, 37, 40, 83, 150,

161 Spencer, C 22, 86 Staal, W 23, 89 Stahmer, A 26, 39, 103, 156 Steele, S 25, 27, 37, 100, 108,

151 Stein, T 22, 85 Stephens-Groff, S 17, 66, 42, 174 Sterling, L 37, 150 Stevenson, R 22, 88 Stewart, W 14, 49 Stodgell, C 38, 155 Stone, J 19, 21, 32, 72, 81, 126 Stone, V 14, 50 Stone, W 35, 139, 141 St-Onge, J 21, 81 Stout, J 40, 164

Sullivan, M 34, 134 Sutcliffe, J 27, 111, 112 Sutton, S 13, 43 Suwa, K 19, 73 Swanson, A 35, 141 Sweatt, J 22, 86 Sweeney, J 37, 151 Swensen, L 27, 111 Swettenham, J 41, 165 Szatmari, P 28, 31, 33, 34, 113,

124, 132, 133

T

Tager-Flusberg, H 16, 25, 26, 27, 36, 37,

48, 52, 58, 99, 100, 106, 108, 109, 110,

146, 148 Takeoka, M 33, 131 Tasse, M 25, 103 Taylor, C 34, 134, 137 Tazoe, M 33, 34, 131, 136 Thatcher, K 22, 89 The ASD-CARC Epidemiology Project Team

20, 77

Theiner-Schumacher, P 40, 164 Thevarkunnel, S 38, 152 Thomas, K 17, 62 Thompson, W 20, 78 Thys, M 17, 66 Ticinetti, T 22, 85 Tisdale, B 38, 155 Todd, R 32, 127 Tojo, Y 26, 35, 107, 142 Toth, K 16, 58 Travis, L 34, 136 Trepagnier, C 14, 49 Tsao, L 26, 104 Turner, L 35, 139, 141 Tyler, J 21, 84

U

Ulman, T 35, 139, 141

I M F A R

Author Index

184

V

Van Berckelaer-Onnes, I 17, 42, 65, 171 van Daalen, E 15, 18, 23, 54, 68, 69,

89, 91 Van de Water, J 42, 174 van der Grond, J 18, 68 van der Meere, J 37, 149 van Engeland, H 13, 15, 18, 23, 25, 36,

37, 47, 54, 68, 69, 89, 91, 99, 145, 147

Van Hulle, C 32, 127 Vance, D 33, 130 Vangel, M 27, 108 Verlaan, D 21, 81 Verté, S 37, 149 Vidal, J 18, 67 Villalobos, M 13, 32, 46, 125 Vismara, L 42, 171 Vitale, M 24, 98 Volden, J 16, 60 Volkmar, F 16, 28, 37, 58, 115, 148 Vorstman, J 23, 89

W

Wagle, R 22, 88 Wagner, G 34, 135 Wakefield, A 42, 171, 173, 42, 174 Wallace, G 17, 36, 64, 145 Walrath, C 24, 94 Wang, A 16, 59 Wang, L 40, 161 Wang, N 41, 169 Ward, M 38, 152, 42, 174 Warreyn, P 26, 106 Watson, L 35, 142 Watt, N 28, 117 Webb, S 31, 121, 122 Webb, T 24, 96 Weeber, E 22, 86 Wei, T 34, 136 Weisblatt, E 41, 166 Weissman, A 40, 161 Wess, M 24, 96 Wetherby, A 28, 116, 117 Whalen, C 28, 114 Wheelwright, S 26, 40, 107, 162 White, K 42, 170

Whiten, A 13, 44 Whitney, E 38, 153 Wier, M 24, 97 Wiersema, J 37, 149 Wiggins, L 24, 96 Wightman-Hertz, S 15, 54 Wilbarger, J 14, 48 Wilkes, K 21, 81 Willemsen-Swinkels, S 15, 18, 23, 54, 68, 69,

91 Williams, D 16, 18, 58, 59, 70, 71 Williams, J 13, 44 Williamson, P 25, 100 Wills-Karp, M 36, 143 Wilson, L 15, 17, 53, 64, 65 Wilson, R 14, 51 Wilson, S 24, 96 Wines, R 20, 77 Winkielman, P 14, 48 Winrow, C 29, 118 Winter, J 33, 129 Wojcik, J 24, 97 Wolpert, C 19, 28, 33, 72, 112,

116, 130 Wong, D 32, 126 Woods, J 28, 116, 117 cWright, H 19, 21, 23, 28, 33, 36,

72, 80, 84, 90, 112, 116, 130, 146

Wu, C 35, 138

Y

Yamagata, T 19, 22, 73, 86 Yang, T 26, 104 Yeargin-Allsopp, M 20, 78 Yechiam, E 40, 164 Yirmiya, N 34, 40, 133, 160 Yoder, P 34, 137 Yonan, A 32, 126 Yorbik, O 18, 68 Yoshida, C 20, 24, 76, 97 Yost, K 37, 148 Yu, C 20, 77 Yu, W 22, 86

I M F A R

Author Index

185

Z

Zachary, A 21, 84 Zahorodny, W 18, 23, 24, 67, 91, 98 Zandi, P 23, 89 Zeegers, M 18, 68 Zhang, H 38, 154

Zhang, W 21, 82 Ziegler, D 33, 131 Zimmerman, A 21, 84 Zlotkin, S 16, 61 Zuddas, A 16, 60 Zwaigenbaum, L 28, 31, 33, 34, 113,

124, 132, 133

I M F A R

Notes

186

I M F A R

Notes

187

I M F A R

Notes

188

I M F A R

Notes

189