Colorado Journal of Psychiatry & Psychology...practice,research, training, and professional...

5 Experiences in Academic Medicine: A Pilot Survey of Early Career Faculty in Pediatric Mental Health

18 AdherenceinAdolescentTransplantPatients: ExploringMultidisciplinaryProviderPerspectives 30 Regression, Depression, and Psychosis in a Young Adult Female with Down Syndrome: A Case Report 36 AMultidisciplinaryApproachtotheTreatment of Comorbid Neurodevelopmental and Medical Problems

43 AComprehensiveTransdiagnosticApproachto Pediatric Behavioral Health 58 InfantandPreschoolAdaptationsofInhibitory Adult Tasks Associated with Psychiatric Illness 75 SleepSpindlesandAuditorySensoryGating:Two MeasuresofCerebralInhibitioninPreschool- Aged Children are Strongly Correlated

ColoradoJournalof Psychiatry&PsychologyChild and Adolescent Mental Health

Volume 2 Number 1 January 2017

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School of MedicineDepartment of PsychiatryUniversity of Colorado Anschutz Medical Campus

This second issue of the Colo-rado Journal of Psychiatry and Psychology takes us into the depths of a vibrant academic pediatric mental health pro-gram. Topics covered include research (translational neu-roscience; Calvin et al, Wei et al), the challenges of being an early-career faculty member at a large medical university and major children’s hospital (Germone et al), forging new approaches to designing clini-cal services (Kelly et al, Towhy et al), and the details of clinical practice (Patel et al, Kaur et al). As our most-respected interna-tional mental health journals have appropriately turned their attention to disseminat-ing the best science, we rarely see such a mix of papers. And while through this approach we gain invaluable insights into the science of our field, what we lose out on is a publication that

serves as an accurate reflec-tion of the day-to-day realities of an academic mental health program. That is not the case in this issue of the Journal. These papers, written by our faculty and trainees, serve to ground us in these realities, and remind us that excellence in research, service develop-ment, and clinical care are inextricably linked, making this issue of the Journal an enlight-ening and important read.

- Douglas Novins

EditorialStaff

Douglas K. NovinsEditor-in-Chief

Emily EdlynnAssociate Editor

Marissa SchielAssociate Editor

Melissa MillerEditor/Designer

The Colorado Journal of Psychiatry and Psychol-ogy will again be accepting papers with a focus on child and adolescent mental health for an issue to be published in 2017. A more detailed call for papers will be posted on the Journal website in early 2017.

Call for Papers on Children’s Mental Health

The value of experience is not in seeing much, but in seeing wisely.—William Osler

CopyrightinColoradoJournalofPsychiatryandPsychologyisownedbyRegentsoftheUniversityofColorado,abodycorporate,2015. ThisisanOpenAccessjournalwhichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Copyrightineacharticleisretainedbyeachindividualauthor.

This issue is dedicated to the memory of Professor Randy Ross, who passed away as this issue was coming to press. Randy was an intellectual leader of our extensive developmental research portfolio at the University of Colorado and a highly-respected scientist. Please see Randy’s bios-ketch on page 90 and the full text of this dedication on page 93.

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Child and Adolescent Mental HealthTABLE OF CONTENTS

18 AdherenceinAdolescentTransplantPatients:ExploringMultidisciplinary ProviderPerspectives Sarah L. Kelly, PsyD; Elizabeth Steinberg, PhD; Cindy L. Buchanan, PhD

30 Regression, Depression, and Psychosis in a Young Adult Female with Down Syndrome: A Case Report Lina Patel, PsyD; Elise M. Sannar, MD

5 Experiences in Academic Medicine: A Pilot Survey of Early Career Faculty in Pediatric Mental Health Monique Germone, PhD; Laura Judd-Glossy, PhD; Jessica Malmberg, PhD; Julia Barnes, PhD; Lisa Costello, PhD; Marissa Schiel, MD, PhD; MaryAnn Morrow, PMHNP-BC; Scott Cypers, PhD

36 AMultidisciplinaryApproachtotheTreatmentOfComorbid Neurodevelopmental and Medical Problems Harpreet Kaur, PhD; Monique Germone, PhD; Marissa Schiel, MD, PhD; Emily Edlynn, PhD

75 SleepSpindlesandAuditorySensoryGating:TwoMeasuresofCerebral InhibitioninPreschool-AgedChildrenareStronglyCorrelated Peng-Peng Wei, MD; Sharon K. Hunter, PhD; Randal G. Ross, MD

43 AComprehensiveTransdiagnosticApproachtoPediatricBehavioralHealth Eileen Twohy, PhD; Jessica Malmberg, PhD; Jason Williams, PsyD

58 InfantandPreschoolAdaptationsofInhibitoryAdultTasksAssociatedwithPsychiatric Illness Elizabeth Calvin, MD; Amanda Hutchinson, MD; Randal G. Ross, MD

4 WorkingTogether:CollaborationinAcademicPediatricMentalHealth Marissa Schiel, MD, PhD; Emily Edlynn, PhD

84 ContributorstotheJournal

93 Acknowledgements,Dedication

Editorial

WorkingTogether:CollaborationinAcademic Pediatric Mental Health

From the Editorial Staff: Marissa Schiel, MD, PhD; Emily Edlynn, PhD

We are thrilled to complete this second issue of the Colorado Journal of Psychiatry and Psychol-

ogy.Aswereflectedonourcollectionofarticles,werealized that a central theme of this issue is collabo-ration across disciplines and levels of training. Col-laboration touchedeveryaspectof this issue, fromtheeditorialteam’scomposition,tothediverserep-resentationamongreviewersandauthors,andtothecontentof thearticles themselves, coveringclinicalpractice, research, training, andprofessional devel-opment. We believe the breadth and depth of this collaborationenrichesthequalityofworkpresentedandmakestheJournalmoremeaningful toreaderswith a variety of backgrounds and experiences.

Multidisciplinarycollaborationisnotanewconceptand has long been hailed as the standard of care, despite the real-world challenges of providing truemultidisciplinarycare(eg,cost,infrastructure).1Thislongstanding emphasis is taking on new urgency, however, in our shifting health care system, whichis inaslow-burningcrisisof inefficientsystemsandincreasing costs. As assessment and modificationofhealthcare servicesbecomecentral to justifyinginterventions, reducingcosts,and improvinghealthoutcomes,the importanceof integratingbehavioralhealthwithtraditionalmedicalcarehasgainedtrac-tion. For example, the Centers for Medicare andMedicaid Services (CMS) has recently proposed a“psychiatric Collaborative Care Model” that wouldprovide coverage for an integrated team of a primary care physician, behavioral health care manager, and consultingpsychiatrist.2Thiscommendablestepfor-warddemonstratesprogressinrecognizingthecriti-cal link between behavioral and physical health3 as well as between behavioral health providers of dif-ferent disciplines.

Inthis issueoftheJournal,Kellyetalsurveymulti-disciplinary transplant treatment team members on their perceptions of medical adherence in adoles-

centspost-transplant,whichunderscorestheimpor-tanceofcollaborationamongthemedicalandbehav-ioral health providers of these teams as they strive to improvecarefortheircomplexpatients.The2casestudies by Patel and Sanner, and Kaur et al further elucidatethesignificanceandcompoundedvalueofinvolvingmultipledisciplinesandtypesof interven-tions toachievepositiveoutcomes forverycompli-catedclinicalsituations.

Collaboration is not isolated to the clinical world.Research, scholarship, and clinical service delivery can be closely linked, especially in academia. Thus, practicingcollaborationacrossdisciplinesandlevelsoftraininghasthepotentialforabidirectionaltrans-actionbetweenscholarshipandclinicalpractice.Thepaper by Germone and colleagues in this issue de-scribes a survey of early career faculty with results that are very salient in this era of academic expec-tations collidingwith clinicalproductivitydemands.The unsurprising theme that junior faculty struggle tofindopportunitiesforacademicpursuitsfitswiththemissionofthisJournal:tocreateaccessibleop-portunitiestohoneacademicskillsandshareschol-arly work. It also highlights the importance of senior faculty involving junior faculty in scholarship and the role formentorship in supporting junior faculty ca-reer development. All the papers in this issue exem-plifythesevaluesofcollaboration,mentorship,andinclusionby spanningeitherdifferentdisciplinesorlevels of experience, or both.

TheinauguralissueofthisJournalcelebratedbreadthanddepthofexpertiseinchildandadolescentmen-talhealthandhowtochannelthisexpertiseintoac-tionby followinga strategicplan toelevatequalityof and access to behavioral health services for chil-dren,adolescents,andfamilies.Thisfollow-upissue’stheme of multidisciplinary collaboration speaks tothemechanismforchannelingexpertiseintoaction:working together.

References 1. HoustonJM,MartiniDR.Thedeliveryofmentalhealthcare:whereareweandwherearewegoing?JAmAcadChildAdolescPsychiatry.

2013Nov;52(11):1128-30.2. UnützerJ,HarbinH,SchoenbaumM,DrussB.TheCollaborativeCareModel:AnApproachforIntegratingPhysicalandMentalHealthCare

in Medicaid Health Homes. Medicaid.gov. https://www.medicaid.gov/state-resource-center/medicaid-state-technical-assistance/health-homes-technical-assistance/downloads/hh-irc-collaborative-5-13.pdf. Accessed October 11, 2016.

3. Vreeland.Bridgingthegapbetweenmentalandphysicalhealth:Amultidisciplinaryapproach.JClinPsychiatry.2007;68Suppl4:26-33.

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Germone, Judd-Glossy, Malmberg, Barnes, Costello, Schiel, Morrow, Cypers

Experiences in Academic Medicine: A Pilot Survey of Early-CareerFacultyinPediatricMentalHealth

Introduction

Careersinacademicmedicinecanofferexcitinganddiverseopportunities,includingdirectpa-

tientcare,scholarlyactivities,teaching,andleader-ship.Theseopportunitiesrequiresubstantialinvest-mentsofintellectualenergy,effort,andtime.Asaresult,newfacultymayfinditchallengingtosuc-cessfullyfulfilltheirdiverseroleswithinacademicmedical centers.1,2Variouspersonalandinstitutionalfactors, such as perceived failure of department leadershiptofosterasupportiveclimate(ie,inclu-siveness,respect,andopencommunication),lackofprofessionaldevelopmentopportunities,lim-itedrecognitionandsupportforexcellenceinbothteachingandclinicalcareataninstitutionallevel,and>50%ofprofessionaltimedevotedtopatient

care may lead to high faculty turnover.3Significantconcerns have been raised regarding the fact that asmanyas82%ofnewfacultyintheUnitedStatesseekemploymentinanotherinstitutionwithintheirfirstyearofemployment.4 To prevent turnover and support new faculty, the following areas were identifiedintheliteratureasessential:supportofwork-lifebalance,5,6 clear understanding of career expectations,5,7-9adequatementorshipofnewfac-ulty,4,10-12 and knowledge of the amount and avail-abilityofinstitutionalresources.8,13

Work-Life BalanceAchievingasenseofsatisfactionwiththerelativedistributionoftime,energy,andresourcesdedi-cated to one’s professional and personal goals is

Monique Germone, PhD; Laura Judd-Glossy, PhD; Jessica Malmberg, PhD; Julia Barnes, PhD;

Lisa Costello, PhD; Marissa Schiel, MD, PhD; MaryAnn Morrow, PMHNP-BC; Scott Cypers, PhD*

AbstractObjective. Building a successful career in academic medicine is challenging. The purpose of this study was to surveyacohortofearly-careerfacultyregardingtheirperceptionsofresourcesavailabletothemtosupporttheir clinical, teaching, and scholarly pursuits. Methods.AnonlinequestionnairewasemailedviaSurveyMonkeyto22early-careerfacultymembersatthePediatricMentalHealthInstituteatChildren’sHospitalColoradoandtheUniversityofColoradoSchoolofMed-icine.Participantswereaskedtoindicatetheirperceptionofavailabledepartmentalsupportsinthefollowingdomains:work-lifebalance,initialcareerexpectations,mentorship,andresourcesforearly-careerfaculty.Results.Fifteenof22questionnaires(68%)werecompletedandreturned.Participantsincluded8psycholo-gists(53%)and7medicalfaculty(MDs/DOsandAPNs;46%).Early-careerfacultyreportedmixedexperiencesofachievingawork-lifebalance.Participantsreportedfeelingthemostpreparedtomeettheclinicalexpecta-tions,yetnotthescholarlyexpectationsoftheirposition.Mostparticipantsindicatedthattheyhadanestab-lishedmentorandwereunsureifthedepartmentofferedsupportsforscholarlyendeavors.Conclusions.Theresultsofthecurrentsurveydemonstrateacontinuedneedforsupportsofearly-careerfac-ultyinthedomainsofwork-lifebalance,initialexpectationsofworkinginacademicmedicine,mentorship,andresources for being successful as a faculty member.

*Author Affiliations: Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine, Pediatric Men-

tal Health Institute, Children’s Hospital Colorado.

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Survey of Early Career Faculty

an especially salient issue for faculty as they navi-gatetheformativeyearsoftheircareer.5,6 Having a senseofcontrol,achievedpartiallythroughsettingclear scheduling boundaries for work and personal activities,isakeypredictoroffacultysatisfaction.6 Additionally,havingasenseofsupportfromone’sinstitutionthroughprogramsandinstitutionalpoli-ciesregardingflexibleworkloadarrangements(ie,telecommuting),schedules,andoptionsaroundone’spromotionclock,areimportant.6

Initial Career ExpectationsAcross disciplines, many studies have found that new facultymembersareenthusiasticandeagertobegintheirnewpositionswithinacademicsettings.8 How-ever,manyearly-careerfacultymembersalsofeelunpreparedforthemultiplerolesandresponsibilitiesentailedintheirpositions(eg,clinicalwork,teach-ing,scholarship),whichcanultimatelyleadtojobandcareerdissatisfaction.7,8 Based on the literature, thislackofpreparationappearstostemprimarilyfromlimitedunderstandingofresponsibilities,whichmay be exacerbated by a lack of relevant training and careerpreparationingraduateprograms.9Specifically,limitedknowledgeabouttheexpectationsforpromo-tionisthemostcommoncomplaintintheliterature.5 Despitehavingunclearexpectationsforjobsuccess,manynewfacultymemberssethighexpectationsfor their performance across all domains.8 These self-imposedstandardsmaybereinforceddirectlyorindirectly by supervisors and department leaders.8 However,newfacultymembers’perceptionoftimeconstraintsandchallengesinmanagingcompetingresponsibilitiescannegativelyimpacttheirabilitytoconsistentlymeettheseexpectationsforsuccess.7,8

MentorshipResearch has demonstrated that mentoring has an importantinfluenceonafacultymember’sscholarlyproductivity,careermanagement,collegialnetwork-ing,andcareersatisfaction.4,10Unfortunately,arelativedearthofempiricalliteratureexistsontheprocessofmentoringearly-careerfacultymembersinacademicmedicine.Thetraditionaldyadmodel,where a senior faculty member mentors a junior faculty member, has consistently been shown to be the most common mentorship model, although peer mentoring has become increasingly popular.11 The

mostcommonmentoringactivityreportedisregularmeetingsbetweenmentorsandmentees,withthefrequencyofmeetingsrangingfromweeklytotwiceyearly.10Whilethebenefitsofmentorshipareevident,concerns regarding the sustainability of mentorship models have been raised, given increasing clinical re-sponsibilities,reductionofallocatedtimeforscholarlyactivities,andadeclineofavailableseniorfacultytoserve as mentors.12

Resources for Early-Career FacultyResearchhasindicatedthatnewfacultyrequiresup-port to establish their roles as teachers, scholars, and researchers.8,13 Historically, new faculty have reported lowerwork-relatedsatisfactionandincreasedwork-relatedstressastimepasses.8 Clear guidelines and support from a faculty member’s department and the senior faculty are important for junior faculty career developmentandsatisfaction.8,13,14 In a survey of residents, fellows, and junior and senior faculty mem-bers, Kubiak et al14foundthatinadditiontomentor-ing,respondentsrequestedguidelinesandsupportstoaddressfinancialchallengessuchasassistancewithdebt management, pilot funding for scholarship and research,andacademicskillsacquisition(eg,teach-ingandpresentationskills,andprotectedtimeforresearchandscholarlyactivities).

Current AimsThe current paper examines the needs of new fac-ultymembersat1academicmedicalinstitutionbysurveyingearly-careerfacultyontheirapproachestoandperceptionsofinstitutionalsupportforwork-lifebalance,knowledgeofinitialcareerexpectations,adequatementorship,andfinally,accessibilityofresources. The authors were interested in discover-ingtheextenttowhichnewfaculty(ie,academicappointmentwithinthepast5years)atthePediatricMentalHealthInstitute(PMHI,partofChildren’sHos-pitalColoradoandtheUniversityofColoradoSchoolofMedicine)balancedthedemandsoftheirworkresponsibilitiesandreceivedsupportasearly-careerprofessionals. The faculty members at the PMHI represent a variety of disciplines including psychiatry, psychology,andadvancedpracticenursing,andholdprimary faculty appointments within the Department ofPsychiatryattheUniversityofColorado’sSchoolof Medicine. The PMHI now has more than 60 faculty

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members(46atthetimeofthissurvey)andprovidesacontinuumofpsychiatricservicesincludingoutpa-tient,partialhospitalization,inpatient,consultation-liaison, and emergency services to children and adolescents.Theauthorsinvestigatedwhetherearly-careerfacultyfeltsupportedincriticalareasnecessaryforcareergrowth,andhowsatisfiedtheywerewiththesupporttheyreceivefromtheinstitution.Thissurveyaimedtodiscoverareasofstrengthwithinourinstitution,aswellastoidentifyareasinwhichtorecommendimprovement.

Methods

SampleThesamplewascomprisedofearly-careerfacultywithintheirfirst5yearsofinitialappointmentatthePMHI.Atthetimeofthesurvey,thisinstitutehadatotal of 46 faculty members, comprised of psychia-trists,advancedpracticenurses,andpsychologists.Atotalof22early-careerfacultymetcriteriaforinclu-sionandwereinvitedtorespondtothesurvey(48%ofallfacultyatthePMHI).Responseswerereceivedfrom15facultymembers,aparticipationrateof68%.Someparticipantsdidnotprovideanswerstoeveryquestion.Pairwisedeletionwasusedtoaddressmiss-ingdatawhencalculatingpercentagespertainingtothe age and racial ethnic group demographic charac-teristicsofthesample.Demographicquestionswereincludedinthestudytogatherinformationaboutage,sex, race, marital status, number of children, gradu-atedegree(s),post-degreetraining,currentfacultytitle,andpreviousfacultyappointments(Table1).Those who completed the survey were largely female (n=12),white(n=14),andbetween30and39yearsofage(n=12).Mostparticipantsalsoreportedthatthiswastheirfirstfacultyappointment.Intermsofdegreestatus,8participantshadaPhD,3participantshadanAPNdegree,and4participantshadaDO/MD.Themajorityofparticipantswererankedattheassistantprofessorlevel(n=8),whiletheremaining7partici-pants were ranked at the instructor/senior instructor level(Table1).

Survey DevelopmentThe authors conducted a review of the literature on issuesrelevanttoearly-careerfaculty.Fourareasof

interest were selected for focus in this survey based ontheirsalienceintheliterature:(1)work-lifebal-ance,(2)initialcareerexpectations,(3)mentorship,and(4)resourcesforearly-careerfaculty.Surveyquestionsweredevelopedtoaddresseachoftheseareas(Appendix).The34-questionsurveyincludedasectiononbasicdemographics(9questions);aseriesofquestionspertainingtomentorship(5questions),departmentalsupports(7questions),andwork-lifebalance(7questions);andperceptionofprepared-ness to meet clinical, research/scholarly, and super-visory/teachingexpectations(3questions).Questionresponse sets included the following:1. Forced-choiceanddichotomousquestiontypes

tocollectdemographicdataandtheparticipants’perceptionsoftheavailabilityofparticularpro-gramsorresourceswithinthedepartment(eg,“Mydepartmentoffersanewfacultyorientationprogram,”“Yes,No,orNotSure”).

2. Five-pointLikertscalestomeasurethepartici-pant’sattitudesandopinionsregardingthese-lectedtopic(eg,“Notatall”to“MuchmorethanIwouldlike,”or“Notatallprepared”to“Fullyprepared”).

3. Checkallthatapplyquestionstosolicitasmanyresponsestoquestionsasparticipantsperceivedwereapplicabletothem(eg,“Inwhichways,ifany,doyousetclearwork-lifeboundaries”).

4. Open-endedquestionsthatallowedparticipantstoofferdetailedcommentsontheirexperiences.

SeeAppendixforafulldescriptionofthesurveyintro-duction,questions,andresponsesets.

Survey AdministrationThe survey was programmed into SurveyMonkey for self-administration.Alinktothesurveywasemailed,alongwitharequestforparticipation,toearly-careerfaculty during the Fall of 2015. Within the email, participantswereinformedoftheestimatedlengthoftimetocompletethesurvey(5–10minutes),thattheirresponseswouldremainanonymous,theratio-nalebehindthesurvey(toimprovethesupportsforfacultymembersatPMHI),andthattheresultsmaybepublishedinascholarlyjournal.Theparticipantswere encouraged to contact the research team with questionsorconcerns.Noincentiveswereofferedforparticipation.Participantswereaskedtocomplete

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thesurveywithin1weekandafollow-uprequestwas made 2 days prior to the deadline to encourage a higher response rate.

Data AnalysisData was transferred from SurveyMonkey to SPSS version22.0fordataanalysis.Descriptiveanalysesofresponseswereconductedandopen-endedrespons-eswerereviewedtoidentifykeythemes.Resultsforeachofthemainareasofinquiryaredescribedinthesectionthatfollows.

Results

Work-Life BalanceEightofthe15participantsfelttheirfacultypositionhadallowedthemtoachieveawork-lifebalanceatamoderatetovery-highlevel,whiletheremaining7participantsindicatedhavingachievedconsiderablyless balance than they would like. In responding to waysinwhichtheyachievework-lifebalance,facultyendorsedthefollowingstrategies:(1)protectingspe-cificpersonaltimesinone’sschedule(n=7),(2)check-ingemailonlyatdesignatedintervalsortimes(n=6),and(3)schedulingworktimearoundchildcare(n=5).Whenaskedtooutlineadditionalstrategiesemployedthatwerenotexplicitlylistedinthesurvey,partici-pantsidentifiedstrategiessuchascompletingallworkon-campus,leavingcellphone/pageroffwhennoton-call,notworkingondaysoff,andsettingboundariesaround work hours. For example, one faculty member reported,“Don’tengageinafter-hourstalksoractivi-tiesexceptonlimitedbasisfornationalmeetings.”Mostparticipantsreportedmakingminimalmodifica-tionstotheirprofessionalactivitiesinordertocreatemorework-lifebalance,with8participantsrespond-ingeither“notatall”or“alittle”tothisquestion.Forthose who endorsed having made some level of modi-ficationtotheirprofessionalactivities,thefollow-ingstrategieswereendorsed:(1)engaginginfeweractivitiesforpromotion(n=7),(2)declininginvitationstoparticipateinprofessionalactivities(n=6),(3)se-lectingsupportratherthanleadershiproles(n=5),(4)delayingorpausingthepromotionclock(n=3),and(5)reducinghis/herworkschedule(n=2).Faculty overwhelmingly acknowledged that they havemodifiedtheirpersonallifeinordertoengage

inprofessionalactivities,with11ofthe15partici-pantsindicatingthattheyhadmademoderatetohighmodificationstotheirpersonallives.Alargemajorityof faculty members reported that they got less sleep thanwasideal(n=11);workednights,earlymornings,orweekends(n=4);andspentlesstimeattendingsocialevents(n=12).

Initial Career ExpectationsParticipantsreportedstrongreadinesstoassumetheclinicalexpectationsoftheirpositionswith9par-ticipantsindicatingthattheyfeltpreparedorfullyprepared to meet the clinical demands of their role. Participantsendorsedmoderatereadinesswithre-gardstofulfillingteaching/supervisoryexpectations,with7participantsfeelingprepared/fullyprepared.Only2participantsfeltprepared/fullypreparedtoaccomplishresearch/scholarlyexpectationsrequiredoftheirpositions.Participantsnotedfeelinglargelydissatisfied(n=11)withtheamountoftimetheyareallottedtoaccomplishalltasksrequiredofthemintheirprofessionalroles(eg,clinical,research,teach-ing,etc).

MentorshipThemajorityofparticipants(n=11)hadestablishedei-theraformalorinformalmentoringrelationshipwithanotherfacultymember,with2participantsreceivingmentorshipfromanindividualatanotherinstitution.Ofthosewithanestablishedmentoringrelation-ship,11participantsreportedtheyinformallysoughtouttheirmentor.Tenofthe11participantswithanestablishedmentorshiprelationshipreportedtheymeet regularly with their mentor, with the major-ityestimatingthefrequencyofthesemeetingstobeweekly or monthly. The most commonly endorsed ob-jectivesthatfacultyfeltwereimportantinamentor-ingrelationshipincludedassistancewithpromotion(n=13),clarificationregardingdepartment/universityfacultyexpectations(eg,teaching,research,clini-calresponsibilities;n=13),peersupport(n=11),andresearch/scholarlysupport(n=11).Themajorityoffacultymembers(n=10)endorsedfeelingsomewhattoverysatisfiedwiththeirmentor’sabilitytoclearlydelineateuniversityexpectationsregardingacademicpromotionandsupporttheminmeetingtheseexpec-tations.

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Resources for Early-Career FacultyNine faculty members indicated they were unsure or did not believe that there was a new faculty orienta-tionavailabletothem.Ofthosewhoendorsedat-tendinganewfacultyorientation,only2participantsfelt they gained new knowledge regarding programs availableon-campustoassistfacultywithteachingorscholarlyactivities.Whenqueriedastowhetherparticipantswereawareofformalsupport/resourcesavailabletothemforscholarlyactivities,overhalf(n=11)indicatedtheywereawareoftheseresources,while5participantsreportedbeingunsureabouttheavailability of these resources. The overwhelming majorityofparticipantsreportedtheirdepartmentdidnotofferprotectedtimeorgrantopportunitiestosupport them in advancing their research/scholarly activities(n=6),orwereunsureiftheirdepartmentofferedthesesupports(n=8).

DiscussionThe aim of the current pilot was to highlight the cur-rentperceptionsofearly-careerfacultyatanacadem-icmedicalcenter,particularlywithregardtowhethertheyfeltsupportedindomainscriticaltotheircareerdevelopment.Despitethesmallsamplesize(n=15)andlimiteddemographicrange(predominantlywhite,female,ages30–39),theresponsesfromthissurvey are consistent with the literature in regard to newfaculty’sperceptionsofwork-lifebalance,initialcareerexpectations,mentorship,andresourcesforearly-careerfaculty.Overall,participantssurveyedinthisstudycontinuedtoendorsetheneedforsupportinwork-lifebalance;understandingclinical,scholarly,andteachingexpectations;accesstoasenior-levelmentor;andadditionalresourcessuchastimeandmonetary support, especially for scholarly projects. Eachcriticalareaisdiscussedmoreindepthinthesectionsthatfollow.

Work-Life BalanceFindingsfromthissurveysuggestthatself-careactivi-tiesarethemostcommonpersonalsacrificesthatfacultymakeinordertofulfillwork-relatedduties,whichresearchpointsoutcouldnegativelyimpactone’soverallsenseofwell-beingandjobsatisfac-tion.2Specifically,amajorityofparticipantsindictedthat they slept less in order to work during the nights, earlymornings,and/orweekends.Additionally,ama-

jorityreportedreducingthetimetheyspentengagedinrecreationwiththeirfamilies.Facultymembersin this survey expressed interest in working at the institutionalleveltocreatepoliciestosupportwork-life balance. In general, they recommended a need for policiesthatsupportflexibleschedules,streamlinedprocesses for using personal and professional leave time,andmentorshiprelationshipsthataddresswork-lifebalance.Resultsofthissurveysupportfindingsandrecommendationswithinthecurrentliteratureregardingtheimportanceofinstitutionssupportinganopendiscussionofwork-lifebalanceissues,bothforthepersonalwell-beingoftheirfaculty,aswellasfortheproductivityoftheinstitution.Readersarere-ferredtoLeeetal15forrecommendedquestionsthatinstitutionsmayposetofacultytofacilitatesuchdis-cussion, including “am I willing to make the personal sacrificesthatarerequiredtobecomethetoppersoninmyfield–would‘well-respected’begoodenough?”

Initial Career Expectations and MentorshipSurvey results demonstrated that new faculty mem-bers felt most prepared for their clinical responsibili-tiesandleastpreparedfortheirresearch/scholarlyexpectations.Itshouldbenotedthatasclinicaleducators,early-careerfacultywithintheDepartmentofPsychiatryattheUniversityofColoradoSchoolofMedicinehavescholarshipexpectationsthatmayinclude,butarenotlimitedto,researchactivities.Ashiftinacademicmedicinehasbeennotedintheliteraturewithregardstoresearchexpectations.16,17 Authorshavearguedthatacademicinstitutionsshould seek to support faculty’s involvement in teach-ing,dissemination,andapplicationofknowledge(ie,“scholarship”),aswellasmoretraditionalinvesti-gationalresearch.O’Meara16 noted that a common definitionofscholarshiphasbeendifficulttoagreeupon and it is possible that faculty who completed thissurveymayhavebeenunawareofthedistinctionbetween research and scholarship. Given that this surveyspecificallyqueriedfacultyabouttheirper-ceivedabilitytoaccomplishresearchexpectationsanddidnotdirectlyinquireaboutscholarlyexpectations,it is possible that faculty might have reported higher rates of feeling prepared to accomplish their scholarly expectations,incomparisontotheirresearchexpec-tations,hadtheybeenaskedtoreportonboth.

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Knowledgeandsupportaboutthepromotionprocess,which is typically an area of concern for most new facultymembers,continuestobeatargetforongoinginstitutionalimprovements.Additionally,thisinfor-mationhighlightshowaone-size-fits-allmentoring/support approach may not meet the needs of faculty whocomewithdifferentlevelsofcomfort/experi-enceacrossdifferentdomains(eg,clinical,teaching,scholarship).Departmentsmayalsowanttoexploreeffectivewaystobalancethecompetingdemandsfornewfaculty,aswellastheamountoftimeallottedtoeachactivity,asthisseemstobeanareaofperceiveddifficultyforearly-careerfaculty.

Resources for Early-Career FacultyOnthewhole,resultsfromthissectionsuggestaneedto ensure that faculty are aware of the resources that areavailabletothem.Asoverhalfoftheparticipantsresponded that they either did not receive a new facultyorientationorwerenotsureiftheyhad(n=9),thissurveyindicatesthatdepartmentsmaybenefitfromexplicitlylabelinganddefiningnewfacultyorientationprocessesandconsideringthetimingoforientations.Suggestedcomponentsofanewfac-ultyorientationfromtheliteratureincludeinforma-tionregardingthedistinctionbetweenresearchandscholarship,theday-to-dayresponsibilities,andalsoaddressingwaystofosterrelationshipsbetweennewfaculty and the department in which they work.8 Whileinformationaboutthepromotionprocessisbeingprovided,facultymaybenefitfromfurthersup-portinhowtoachievethepromotionrequirements.Timeandmoneyarefiniteresources,soeducatingfaculty on what resources are available to support themmayimproveproductivityandjobsatisfactionasonly1participantacknowledgedthattheseresourcesareavailabletoearly-careerfaculty.

LimitationsTherewereseverallimitationstothecurrentstudyincludingasmallsamplesize,allparticipantscomingfromasingledepartmentwithinasingleinstitution,and exclusivity within the disciples of psychology and psychiatry.Additionally,thesampleisnotdemograph-ically diverse as it is comprised primarily of Caucasian women,ages30–39.Whiletheresultsofthispilotsurveymaynotberepresentativeofallearly-careerfaculty, which limits the generalizability of the study, thefindingsfromthissurveyareconsistentwiththefindingsfrompriorstudiesconductedonthistopic.

Conclusions and Future StudyThe results of the current survey demonstrate a continuedneedforsupportsofearly-careerfacultyinthedomainsofwork-lifebalance,initialexpectations,mentorship, and resources. Survey responses indi-catedthattheconcernsofearly-careerfacultyremainconsistent with those noted in the literature over the past 30 years. While some faculty reported having ad-equatesupport,mostreportedadesiretoreceivead-ditionalsupportsinordertosucceedintheircareers.The faculty who were surveyed expressed an interest inassistancewithwork-lifebalance,preparednessforscholarlyactivities,mentorship,andfeelingconnectedto other faculty. Surveyresultsdepictedapreferenceforinstitutionalsupportformaintainingawork-lifebalance,indi-vidualized and dynamic mentorship experiences, andexplicitcommunicationregardingresourcesandsupportsavailabletoearly-careerfaculty.Whiletheexperiencesofearly-careerfacultyarenowwelldocu-mented in the literature, future studies should con-tinuetoexaminewaysinwhichearly-careerfacultyexperiencescouldbeimproved,andhowinstitutionscanbettersupporttheminestablishingthemselvesasprofessionals within academic medicine.

11


Table 1.DemographicCharacteristicsofCommentarySample(n=15)

Note:Pairwisedeletionwasusedtoaddressmissingdatawhencalculatingpercentages.

Characteristic Number PercentAge30-39 12 85.740-49 1 7.150-59 1 7.1Missing* 1 --GenderFemale 12 80Male 3 20DegreeMD/DO 4 26.6APN 3 20PhD 8 53.3Married/PartneredYes 14 93.3No 1 6.7ChildrenYes 10 66.7No 5 33.3Racial Ethnic GroupWhite 14 100Missing* 1 --Prior Faculty PositionsYes 3 20No 12 80Years with Current Dept<1 year 4 26.71-2years 5 33.32-3years 4 26.73-4years 2 13.3Faculty TitleInstructor 2 13.3Senior Instructor 5 33.3Assistant Professor 8 53.3Years of Post-Degree Training1 Year 7 46.72 years 3 205+ years 5 33.3Training from Current DeptYes 7 46.7No 8 53.3

12


Appendix. Early-Career Faculty Survey

IntroductionWeappreciateyourtimeandsupportofourproject,whichisexaminingtheexperienceofearlycareerfaculty.Pleasenotethatyourresponseswillremainanonymousandthequestionshavebeendesignedtohelpprotectyouranonymity.

Ifthefollowingquestionsaskforyouropinionsregardingyour“department,”thisreferencesthePediatricMentalHealthInstitute(previouslyknownastheDepartmentofPsychiatry&BehavioralSciences)atChildren’sHospitalColorado.

Questionswithanasterisk(*)identifiesaquestionthatrequiresaresponse.

Questions

MentorshipSeveralstudieshaveindicatedthatdevelopmentofamentorrelationshipwhennewfacultymembersarehiredimpactstheoverallsuccessofthosemembers’assimilationintothecultureoftheinstitution,theirjobsatisfaction,andtheirabil-itytosmoothlynavigatetheircareerpath.Pleasetellusaboutyourmentoringexperienceregardingourpresentpositionat PMHI.

1. Haveyouestablishedamentorrelationshipwithanotherfacultymember?(Selectallthatapply)*a. No,Ihavenotestablishedamentorrelationship.b. Yes,Iwasformallyassignedamentorfromthisinstitution.c. Yes,Iinformallysoughtoutamentorfromthisinstitution.d. Yes,Iinformallysoughtoutamentorfromanotherinstitution.e. Other(pleasespecify)

2. Howdoyouaccessmentorshipfromyourmentor?*a. Not applicable. Do not have a mentor.b. Informalpop-inmeetingsc. Communicate primarily through emaild. Do not meet/communicatee. Regularlyscheduledmeetings(pleasespecifyfrequency)

3. Whatobjectivesdoyoufeelareimportantinamentorrelationship?(Selectallthatapply)*a. Promotefacultydevelopment/assistwithpromotionprocess/tenureprocessb. Peer supportc. Liaisonwithothersinthedepartment/regionally/nationallyd. Resourceconcerninguniversity/departmentexpectationsforfaculty(eg,teaching,research,clinicalresponsi-bilities)e. Formal support for research and scholarly workf. Notapplicable.Donotfeelamentorrelationshipisimportantg. Other(pleasespecify)

4. Howhelpfulhasyourmentorbeeninassistingyouwithsocializinganddevelopingcollegialrelationships withyourcolleaguesinthedepartment/regionally/nationally?*

a. Not at all helpfulb. (intermediatechoice)c. Somewhat helpfuld. (intermediatechoice)e. Very helpful

13


5. Howsatisfiedareyouwithyourmentor’sabilitytoclearlydelineatedepartmentexpectationsregardingresearch,teaching,andclinicalresponsibilities?*

a. Veryunsatisfiedb. (intermediatechoice)c. Somewhatsatisfiedd. (intermediatechoice)e. Verysatisfied

Developmental SupportsBelow are some ways a department can support their new faculty. Please think of the supports provided by PMHI/CHCO DepartmentofPsychiatry&Psychologywhenrespondingtothefollowingquestions.

6. Mydepartment(PMHI)offersanewfacultyorientationprogram.*a. Yesb. No c. Not sure

7. ThenewfacultyorientationprogramatPMHIhelpedmetobuildrelationshipswithotherfacultymembers.*a. Yesb. No c. Not sured. NotApplicable.Didnothaveafacultyorientationprogram.

8. ThenewfacultyorientationprogramatPMHIsuppliedmewithinformationaboutteaching,research,andcampusprograms.*

a. Yesb. Noc. Not Sured. NotApplicable.Didnothaveafacultyorientationprogram.

9. My department has a formal support program for research and scholarly work.*a. Yesb. Noc. Not sure

10. Mydepartmentoffersreleasedtimeand/orgrant-in-aidopportunitiestoprovideresourcestoadvanceandstrength-en my research record.*

a. Yesb. Noc. Not Sure

11. Howsatisfiedareyouwiththetimeyouhavebeenprovidedtocompleterequiredtasks(clinical,teaching,supervis-ing,research)?*

a. Notatallsatisfiedb. (intermediatechoice)c. Somewhatsatisfiedd. (intermediatechoice)e. Verysatisfied

12. Haveyoubeenprovidedguidanceaboutthepromotion/tenureprocess?*a. Yesb. Noc. Not Sure

14


13. Howsatisfiedareyouwiththelevelofsupport/guidanceyouhavereceivedinstartingtoaccomplishtenurerequire-ments(teaching,research,committees)?*

a. Notatallsatisfiedb. (intermediatechoice)c. Somewhatsatisfiedd. (intermediatechoice)e. Verysatisfied

Work-Life BalanceForthepurposesofthissurveywearedefiningwork-lifebalanceasasenseofclearboundariesintimeandattentionfocusedonprofessionalversuspersonalactivities.

14. Towhatextenthasyourfacultypositionallowedyoutoachievework-lifebalance?*a. Much less than I would likeb. (intermediatechoice)c. Somewhatd. (intermediatechoice)e. Achieved a very high level

15. Inwhichways,ifany,doyousetclearwork-lifeboundaries(checkallthatapply):*a. Have not set boundariesb. Checkemailonlyatdesignatedintervalsortimesc. Protectspecificpersonaltimesinyourscheduled. Schedulenon-negotiablewritingtimee. Scheduleworktimearoundchildcaref. Other(pleasespecify)

16. Towhatextenthaveyoumodifiedyourprofessionalactivitiestocreatemorebalanceinyourpersonallife?*a. Not at allb. (intermediatechoice)c. Somewhatd. (intermediatechoice)e. Much more than I would like

17. Inwhichways,ifany,haveyoumodifiedyourprofessionalactivitiestocreatemorebalanceinyourpersonallife(checkallthatapply):*

a. Havenotmademodificationsb. Reduced work schedulec. Selected support rather than leadership rolesd. Delayed or paused the tenure clocke. Declinedinvitationstoparticipateinprofessionalactivitiesf. Choseamentorbasedonimpressionsoftheirownwork-lifebalanceg. Engagedinfeweractivitiesforpromotion(eg,teaching,clinicalactivity,research,service,scholarship).Pleasespecify.

18. Towhatextenthaveyoumodifiedyourpersonallifetoengageinprofessionalactivities?*a. Not at allb. (intermediatechoice)c. Somewhatd. (intermediatechoice)e. Much more than I would like

15


19. Inwhichways,ifany,haveyoumodifiedyourpersonallifetoengageinprofessionalactivities(checkallthatapply):*a. Havenotmademodificationsb. Delayed having, spacing when, or choosing to not have childrenc. Get less sleep than is ideald. Worked nights, early morning and/or weekendse. Spentreducedtimeonnightsandweekendsattendingpersonal/familyactivitiesf. Didnotattendcertainpersonal/familyactivities

20. Towhatextentdoyouperceivethattherearepoliciesinplacetosupportadequatework-lifebalance(eg,availabilityofandabilitytouseleavetime;availabilityforcoverage)?*

a. Not at allb. (intermediatechoice)c. Somewhatd. (intermediatechoice)e. Very much

21. Whatwouldmakeiteasiertohavemorework-lifebalanceasanearlycareerfaculty(eg,workingremotely,flexibilityinschedule,researchpartnerships)?*

Expectations

22. Manyacademicpositionsincludeexpectationsforsuccesswithinclinical,research,andsupervisorydomains.Howwouldyoudescribeyourpreparationtomeettheclinicalexpectationsofyourrole?*

a. Not at all preparedb. (intermediatechoice)c. Somewhat preparedd. (intermediatechoice)e. Fully prepared

23. Howwouldyoudescribeyourpreparationtomeetresearchexpectations?*a. Not at all preparedb. (intermediatechoice)c. Somewhat preparedd. (intermediatechoice)e. Fully prepared

24. Howwouldyoudescribeyourpreparationtomeetthesupervisoryexpectations?*a. Not at all preparedb. (intermediatechoice)c. Somewhat preparedd. (intermediatechoice)e. Fully prepared

DemographicsThankyoufortakingthetimetocompletethissurvey.Weappreciateyourresponses.Belowarequestionsregardingdemographicvariables.Youmayanswerasmany,orasfew,asyoulike.Pleasenotethatyourresponseshelpustobetterunderstandourdataandultimatelyinhelpingourdepartment.

25. Agea. 21-29b. 30-39c. 40-49d. 50-59e. 60-69

16


26. Gendera. Male b. Female

27. Racea. Whiteb. Black or African Americanc. AmericanIndianorAlaskaNatived. Asiane. NativeHawaiianorOtherPacificIslander

28. HowmanyyearshaveyoubeenafacultymemberatPMHI/CHCODepartmentofPsychiatry&BehavioralSciences?Pleasedonotincludethetimeyouwereinformaltrainingwiththisdepartment.

a. <1 yearb. 1-2yearsc. 2-3yearsd. 3-4yearse. 4-5years

29. Faculty Titlea. Instructorb. Senior Instructorc. Assistant Professord. Associate Professore. Full Professorf. Other(pleasespecify)

30. Degreea. MDb. APNc. PhDd. PsyDe. Other(pleasespecify)

31. YearsofPost-DegreeTraininga. 1 yearb. 2 yearsc. 3 yearsd. 4 yearse. 5+ years

32. Didyoureceiveanyportionofyourtraining(pre-degree,post-degree,orboth)atPMHI/CHCODepartmentofPsy-chiatry&BehavioralSciences?

a. Yesb. No

33. Married/Partnereda. Yesb. No

34. Childrena. Yesb. No

17


References

1. PololiLH,KrupatE,CivianJT,AshAS,BrennanRT.Whyareaquarteroffacultyconsideringleavingacademicmedicine?Astudyoftheirper-ceptionsofinstitutionalcultureandintentionstoleaveat26representativeU.S.medicalschools.Acad Med.2012;87(7):859-869.

2. NyquistJG.Facultysatisfactioninacademicmedicine.New Directions for Institutional Research.2000;2000(105):33-43.3. BucklinBA,ValleyM,WelchC,TranZV,LowensteinSR.Predictorsofearlyfacultyattritionatoneacademicmedicalcenter.BMC Medical

Education.2013;14(1):1-7.4. KahanovL,EbermanL,IdlewineT,MeltonL.Clinicalacademicfacultyperceptionsofacademicmentorshipinthehealthprofessions.J Allied

Health.2013;11(4):1-10.5. EddyPL,Gaston-GaylesJL.Newfacultyontheblock:Issuesofstressandsupport.J Hum Behav Soc Environ.2008;17(1/2):89-106.6. HarrisB,SullivanA.Work-lifebalanceinacademiccareers.The School Psychologist.2013;67(2):23-26.7. HillNR.Thechallengesexperiencedbypretenuredfacultymembersincounseloreducation:Awellnessperspective.Counselor Education

and Supervision.2004;44(2):135-146.8. SorcinelliMD.Effectiveapproachestonewfacultydevelopment.J Couns Dev.1994;72:474-479.9. CawyerCS,SimondsC,DavisS.Mentoringtofacilitatesocialization:Thecaseofthenewfacultymember.Int J Qual Stud Educ.

2010;15(2):225-242.10. KashiwagiDT,VarkeyP,CookDA.Mentoringprogramsforphysiciansinacademicmedicine:Asystematicreview.Acad Med.

2013;88(7):1029-1037.11. Binkley PF, Brod HC. Mentorship in an academic medical center. Am J Med.2013;126(11):1022-1025.12. PololiL,KnightS.Mentoringfacultyinacademicmedicine:Anewparadigm?J Gen Intern Med.2005;20:866-870.13. RushSC,WheelerJ.Enhancingjuniorfacultyresearchproductivitythroughmultiinstitutioncollaboration:Participants’impressionsofthe

schoolpsychologyresearchcollaborationconference.J Sch Psychol.2011;26(3):220-240.14. KubiakNT,GuidotDM,TrimmRF,KamenDL,RomanJ.Recruitmentandretentioninacademicmedicine-Whatjuniorfacultyandtrainees

want department chairs to know. The American Journal of the Medical Sciences.2012;344(1):24-27.15. LeeC,ReissingE,DobsonD.Work-lifebalanceforearlycareerCanadianpsychologistsinprofessionalprograms.Canadian Psychology.

2009;50(2):74-82.16. O’MearaK.Encouragingmultipleformsofscholarshipinfacultyrewardsystems:Haveacademicculturesreallychanged?New Directions for

Institutional Research.2006;2006(129):77-95.17. Boyer E. Scholarship reconsidered.Princeton,N.J.:CarnegieFoundationfortheAdvancementofTeaching;1990.

18

Adolescent Transplant Adherence: Provider Perspectives

AdherenceinAdolescentTransplantPatients:ExploringMultidisciplinaryProviderPerspectives

Introduction

Solidorgantransplantationisalife-savingtreat-mentoptionformanyacuteandchronicend-

stagediseaseswithdramaticallyimprovedsurvivalrates and outcomes over the past few decades. Though a transplant increases longevity and im-provesqualityoflife,itisalsobestconceptualizedasachronicillnessrequiringstrictadherencetoacomplexpost-transplantmedicalregimen.1 Postop-eratively,itrequirestwice-dailylife-longimmuno-

suppressantmedications,frequentlaboratoryblooddraws,closemedicalfollow-up,andunpredictablehospitalizationsforinfectionorrejectionepisodes,among other medical cares. Medical adherence has beendefinedas“theextenttowhichaperson’sbe-havior—takingmedication,followingadiet,and/orexecutinglifestylechanges,correspondswithagreedrecommendationsfromahealthcareprovider.”2 Adherenceisacomplexhealth-relatedtaskthatisessentialforlong-termgraftsurvivalinpediatricsolidorgantransplantrecipients.Definitionsofgraft

Sarah L. Kelly, PsyD; Elizabeth Steinberg, PhD; Cindy L. Buchanan, PhD*

AbstractIntroduction. Solidorgantransplantationisviewedasachronicillnessthatrequiresstrictadherencetoacom-plexpost-transplantmedicalregimen.Adolescenttransplantrecipientsaremostatriskforseriousandpoten-tiallyfataloutcomesasaresultofpoormedicationadherence.Thereareseveralpsychosocialandbehavioralfactorsthatcontributetononadherence,butfewwell-studiedpsychologicalinterventionsexist.Providerper-spectivesarecrucialtounderstandingtheuniqueneedsofthispopulationtoinformeffectiveandacceptableinterventions.Methods.An11-itemquantitativeandqualitativesurveywasdevelopedandcompletedby34transplantpro-vidersamongthepediatricheart,liver,andkidneyteamsatachildren’shospitalaspartofaqualityimprove-ment project. Results.Providersreportedthatintheirexperiencemostadolescentsstrugglewithadherence(67%)andindicatedthattheydedicateagreatdealoftime,emotionalenergy,andclinicalresourcestoaddressnonad-herence—givenitsseriousconsequences.Providersidentifiedfactorstheybelievecontributetoadherenceintheiradolescentpatients,suchasforgetting/poorplanning,emotionalandbehavioralproblems,familycon-flict,andpoorparentalmonitoring.Theyofferedsuggestionsforimprovedadherenceassessmentaswellasbehavioralinterventionsaimedatimprovingadherence,suchaspeersupportgroups,perhapsdeliveredviavideoconference,tomakethemaccessibletothisgeographically-dispersedpopulation.Discussion.Pediatrictransplantprovidersrecognizetheneedforidentificationofnonadherence,standardizedassessmentofassociatedriskfactorsfornonadherence,andinnovativetreatmentoptionsforthisvulnerablepopulation.ResultsofthisqualityimprovementprojectinformedchangesinhowTransplantPsychologycollab-orates with the solid organ transplant teams to assess and treat adherence in the pediatric transplant popula-tionatourchildren’shospital.

*Author Affiliations: Division of Child and Adolescent Psychiatry, Departments of Psychiatry, (Drs Steinberg and Buchanan) and Pediatrics (Dr Kelly), University of Colorado School of Medicine, Pediatric Mental Health Institute, Children’s Hospital Colorado.

19

Kelly, Steinberg, Buchanan

rejection,survival,andlossorfailurevarybasedonorgan type.3Forthepurposesofthisarticle,acutegraftrejectionistypicallycharacterizedbyrapid,progressivedeteriorationofgraftfunctionassociatedwithspecificpathologicalchangesthatmayberevers-ibleiftreatedpromptly.Chronicrejectionreferstothegradualdecreaseinfunctionofthegraft.Graftsur-vival refers to the success of the transplanted organ andcontraststheterms“graftloss”or“graftfailure,”whicharedefinedasirreversiblelossoffunctionoftheorgan.Inparticular,nonadherencewithimmuno-suppressantmedicationsisassociatedwithseriousandpotentiallyfatalconsequences,includingmedicalcomplications,graftrejectionandfailure,post-trans-plantmortality,andincreasedhealthcareutilizationand costs.1,4

Assessment of AdherenceNonadherence can range in severity, and medical consequencesaredependentondiseaseprocessandhealthstatus.Theterm“nonadherence”isusedthroughoutthisarticletocapturethespectrumofad-herence behaviors, from occasional missed doses of medicationtosignificantlackofadherencetomedica-tionsorothermedicalcare,especiallysince,intrans-plant, even minor lapses in adherence can have nega-tivehealthconsequences.Additionally,adherence,thoughoftenconceptualizedasastablecharacteristic,canchangeovertime,andtypicallyworsensaftertransplant.1,5 Adolescence is a developemental phase markedbysignificantgainsincognitiveandsocioemo-tionaldevelopmentduringwhichmanyhealthyandrisky health behaviors emerge and consolidate. Thus, adherence behaviors and health habits during adoles-cenceestablishatrajectorythathasimplicationsforhealth as an adult.6Researchhasconsistentlyidenti-fiedadolescentsandyoungadultsasthemostat-riskfornonadherencetomedicationregimens.Nonad-herenceinpediatricsolidorgantransplantpatientsisestimatedashighas50%-70%,andcontributestomoregraftlossthanuncontrolledrejectioninadher-entpatients.7-11 The medical impact of nonadherence is staggering for transplant recipients, and nonadher-ence is also related to poor psychological and social outcomes.12 For example, nonadherence in pediat-ric transplant recipients has been associated with decreasedhealth-relatedqualityoflife,socialandschoolactivities,familycohesion,increasedemotionaland behavioral problems, and parental distress.8

Giventheseverityofpotentialconsequencesofnon-adherence and the magnitude of this problem in the adolescentpopulation,pediatrictransplantresearch-ershaveworkedtoidentifytheindividual,family,andenvironmental factors that contribute to nonadher-ence.Thecausesofnonadherencearemultifactorialand exacerbate the burden of the chronic illness itself. RiskandprotectivefactorsaredelineatedwithintheWorldHealthOrganization’s5interrelatedcategories(seeFigure1):Patient-relatedfactors,Socio/economicfactors,Condition-relatedfactors,Therapy-relatedfac-tors,andHealthsystem/HCT-factors.2,7

Patient-relatedfactorsincludemedicationknowledge;understandingofdisease;forgetfulness;cognitiveabilities;self-esteem;emotional,behavioral,social,andschoolfunctioning;andcoping.13Additionally,patient-relatedfactorsassociatedwiththecriticalandnormativedevelopmentaltasksofadolescence,includingestablishingautonomyandself-identity,cancontribute to adherence or nonadherence, such as perceivedinjustice,senseofimmortality,peeraccep-tance, and body image.14-15Foryouth,patient-relatedfactors also include family variables, such as caregiver supervision(eg,lackofmonitoringofmedication-takingversusparentalanxietyandoverprotection),familyenvironment,communication,parentalmentalhealth, and social support.7,8Socioeconomic-relatedfactors include socioeconomic status, health literacy, stability of housing, health care insurance, and medi-cationcost.Factorsrelatedtocondition,therapy,andhealthcareincludeseverityanddurationofillness,

Figure 1. The 5 dimensions of adherence2

20


treatmentregimencomplexity,sideeffects,trustandcommunicationwithhealthcareteam,amountofhealthinformationandfollow-up,healthbeliefs,andaccess to care; these factors are especially important to consider given the common bias in prior research tofocusmoreattentiononpatientorfamilialchar-acteristicsascontributorstononadherencewithlessinvestigationintohealthcaresystemcontributorstononadherence.7

Othertransplantresearchhasinvestigatedadolescentandparentreportsofbarrierstomedicationadher-ence,indicatingthedomainsofdiseasefrustration/adolescentissues,regimenadaptation/cognitiveissues,andingestionissues(eg,inabilitytoswallowmedications,badtastingmedicine,etc).16 Higher se-lectionofbarrierswasrelatedtononadherence,andbarriersarestableovertimeandunlikelytodecreasewithoutintervention.17-21Nonadherence is more likely whenadolescentsarefullyresponsibleformedicationadministration(ratherthanparents),andadherenceissignificantlyworsewithmorningdosesthanwithevening doses.20 Adolescents tend to report more emotionalandsocialbarrierstoadherence,whileparentstypicallyidentifiedmorechallengeswithregi-menadaptationandcognitivebarriers.21 Furthermore, commonpatternsofnonadherenceintransplantre-cipientsfallinto3distinctprofiles:(1)accidentalnon-compliers,orthosewhostrugglewithorganizationandforgetfullness;(2)invulnerablenon-compliers,or those who do not believe they need to take their medication;and(3)decisivenon-compliers,orthosewho independently decide not to adhere.22

Interventions for NonadherenceInterventionsforchildrenandadolescentswithchronic illness typically address adherence with behavioral,educational,andorganizationalstrate-gies, with many treatments combining 2 or more of these approaches.23Ameta-analysisbyGravesandcolleagues23foundthattheeffectsizeacrossalloftheadherenceoutcomesforgroupdesigninterventionstudieswasinthemediumrange,andsingle-subjectdesignstudies’effectsizewasinthelargerange,dem-onstratingthatadherenceinterventionsareeffectivefor increasing adherence. Furthermore, treatments mustbeattentivetodevelopmentalaspectsofcare,healthbeliefs,andculturalconsiderations.15,24-25 How-ever, there remains a paucity of research into the cre-

ationandsystematicinvestigationofculturally-anddevelopmentally-sensitivebehavioralinterventionstoimproveadherencespecificallyinpediatrictransplantrecipients. Newinterventionsforyouthwithchronicillnesshavefocusedonutilizingtechnology,suchasmobileap-plications,videoconferencing,andInternet-basedsupport groups, to both increase the possible inter-ventionparticipantsandtoappealtoadolescents’interest in technology.26Utilizingtechnologyinprac-ticecanimprovepatientoutcomes,increaseaccesstocare, and reduce the burden of illness and treatment; teens are a key audience due to their comfort and familiarity with technology.27Youthoftensetphonealarmsformedicationadministration,andtheyhaveeasyaccesstophoneandtabletapplications,includ-ingsoftwaretoencouragemedicationmonitoringand electronic reminders. Indeed, electronic remind-ershavedemonstratedeffectivenessforshort-termadherenceimprovements,thoughlong-termeffectshave not yet been determined.28 There is also wide-spreadpatientacceptancefortelehealth,butthereare challenges in providing these services, especially home-basedtelehealth,includingreimbursement.Nonetheless, progressive changes in the digital health care landscape seem promising for further advances intelehealthreimbursementandimplementation.However, to date, there are no telehealth adherence interventionsfocusedspecificallyonadolescentsolidorgan transplant recipients.

Current Standard of Care When adolescent solid organ transplant recipients are identifiedasnonadherent,oratriskfornonadher-ence, there are several steps that medical teams can take,includingincreasingthefrequencyoflabblooddraws,increasingthefrequencyofoutpatientmedicalvisits,orevenadmittingthepatienttotheinpatientmedicalfloorformedicationadministrationandclosemonitoring.19Transplant-specificeducation,forbothparentsandteens,isanessentialingredientofef-fectiveinterventionsandshouldinvolveclearcom-munication,shareddecision-making,specificgoals,andwritteninformation.19,29However,educationandknowledgearenotsufficienttospurlastingre-sults.7,23,30Thereareothertacticsmedicalstaffcantry,includingattendingtothepatient-providerrelation-ship, simplifying the medical regimen if possible, ad-

21


dressingproblematicsideeffects,praisingadolescentsforevensmallsuccesses,andallowingplentyoftimeforquestions.13,31-32 If medical teams are concerned aboutparentalfunctioningorifsocial,financial,legal,orlogisticalbarriersareidentified,socialworkoftenbecomes more involved.33Inaddition,providersmakeareferraltopsychologyforinpatientoroutpatienthealthandbehaviorinterventionstoprovideindivid-ual or family support and skills training in strategies that will improve adherence.34Ifclinically-concerningemotionalsymptomsareidentified,aformaldiagnos-ticevaluationisconductedtoofferafullassessmentandrecommendationsforclinicalmanagementthatmay include psychology and/or psychiatry services. However,pediatrictransplantcentersvarysignificant-lyintheirproceduresandcapacitytoprovideoptimallevelofcareformanyadolescentsat-riskfornonad-herence,7 and more research is needed to advance the assessment and treatment of nonadherence in adolescent transplant recipients.

Provider PerspectivesProvidertrustandrelationshipsarealsoimportantaspects of adherence for teens with chronic illness.31 Healthcareprovidersserveacriticalroleinidentify-ingadherenceproblems,implementingimmediatestrategiestohelppatients,andreferringfamiliesformore intensive support. However, there is a paucity ofliteratureaboutproviderperspectivesonadher-enceinpediatrictransplantpopulations.Onestudyofpediatric renal transplant recipients assessed physi-cianratingsofreasonsfornonadherenceandfoundthat the primary reasons asserted by physicians were family-relatedvariables—lackofparentalsupervi-sionandparent-childconflict.11Providerperspectivesareinvaluablegiventheirlong-termrelationshipswiththeirpatients,andtheirinputiskeytotargetinterventionsinasuccessfulandsustainablemanner.Researchdemonstratesthatpatienttrustinmedicalteamproviders,aswellassatisfactionwithpsychoso-cial aspects of care, are related to adherence,13 and adolescentsatisfactionandtrustwithhealthcarepro-vidersisrelatedtoproviderhonesty,trust,respectful-ness, and perceived competency.35 While there is an established standard of care for adolescent transplant recipients with adherence problems, there is a lack of researchontheeffectivenessofadherenceinterven-tionsfocusedonorgantransplantrecipients,andevenlessresearchspecificallyfocusedonadolescentsin

thispopulation,despitetheirvulnerability.12, 31,35

Theobjectiveofthecurrentqualityimprovementprojectwastoassessmultidisciplinarytransplantproviderperspectivesofadolescentnonadherenceforapopulationofkidney,liver,andhearttransplantrecipients at a large children’s hospital and pediatric transplantcenter.Anotherobjectiveofthesurveywastoinformfuturepsychologyandmultidisciplinaryprogramming at this transplant center, as there is a needforadditionalbehavioralhealthinterventionsfor adolescents with transplants.18

Methods

SettingOurpediatrictransplantcenterofferskidney,liver,andheartpre-transplantevaluation;single-organtransplantation;andpost-transplantfollow-upcare.The center was established more than 25 years ago and has performed over 400 heart, 200 liver, and 250 kidney pediatric transplants; in 2015, 14 heart, 22 kidney, and 16 liver transplants were performed. Thecenterutilizesamultidisciplinaryteamapproachwith a variety of medical, psychosocial, and support servicestaffinvolvedinthecarefortheover500patientsreceivingongoingtransplantcareatthehospital. Transplant Psychology is integrated into the multidisciplinarytransplantteamsandisastandardcomponentoftransplantinpatientandoutpatientcare.Transplantpsychologyisavailabletoidentify,assess,andtreatadolescentnonadherence.Addition-ally, Transplant Psychology and social work facilitate amonthlyparentsupportgroupinanefforttobetteraddress the psychosocial needs of parents.

ProceduresWedevelopedan11-itemmixedquantitativeandqualitativesurveybasedonadherenceliteratureandclinicalexperience(seeAppendix).Thesurveywasdistributed by email to 61 clinical providers working with heart, liver, and kidney transplant teams to com-plete anonymously. The survey included the following sections:(1)providerknowledgeandperspectivesoncause(s)ofadherencedifficultiesinthispopulation,(2)frequencyofproviderassessmentofadherence,(3)providerestimatesonhowmanypatientsstrugglewithadherence,(4)providerattitudesandexperienc-eswithnonadherenceinadolescentpatients,(5)pro-

22


viderinterventionstoaddresspooradherencedur-ingroutinepatientcontacts,and(6)providerbeliefsabout what would be helpful or necessary to improve adherence in our adolescent solid organ transplant recipients.Thisqualityimprovementprojectwasap-provedbythehospital’sOrganizationalResearchRiskandQualityImprovementReviewPanel.

Analyses Descriptivestatisticsandfrequencieswerecalculatedforquantitativedata.Qualitativedatawereexaminedforthemesandsubthemes,practicalandprogram-maticsuggestions,andexemplarquotestoproviderichdescriptionofproviderperspectivesthroughtheapplicationofgroundedtheoryandopencoding.36

ResultsThe34respondents(55.7%responserate)ofthissurvey included 10 transplant physicians, 7 transplant coordinators(nursesornursepractitioners),3trans-plant surgeons, 2 other physicians, 2 residents/fel-lows,3nurses,1dietician,4socialworkers,1childlifespecialist, and 1 pharmacist. Given that providers in the kidney and liver transplant programs occasionally overlap, 11 work with the heart transplant program, 17 with the liver transplant program, and 16 with the kidney transplant program.

Perceived Adherence Providers reported on the percentage of adolescent transplantrecipientstheybelievehavedifficultieswithmedicaladherence(seeFigure2),withameanestimateof67%.

Providers commonly ask adolescents about medica-tionadherence,with71%indicatingthattheyinquireaboutadherenceveryfrequently,24%frequently,and6%occasionally.Whenaskedabouthowoftentheythink adolescents are being truthful about their ad-herence,32%indicatedfrequently,62%occasionally,and 6% rarely. Providersidentifiednumerousfactorstheybelievecontributetononadherence(seeFigure3).Thenum-ber of factors indicated by providers ranged from 8 to 17 and over 80% of providers selected the top 5 factors:(1)forgetting/poorplanning,(2)emotionalproblems,(3)behavioralproblems,(4)familyconflict,and(5)poormonitoring(ofmedicationtaking)byparents.Additionalreasonsprovidedinopen-endedresponsesincludedlackofparentalemotionalatten-tion/familyenvironment,lackofsociallife,desireforattentionfromhospitalstaff,healthliteracy,and“some[patients]justdon’tseemtocare.”

Addressing Adherence in Clinical PracticeProvidersreportedaddressingadherencein5%-100%oftheirinteractionswiththeiradolescentpatients,withameanof25%ofinteractions(seeTable1).Wewereunabletoidentifyanydifferencesinthepercent-ageofinteractionsaddressingadherencebyprovidertype or organ type.Almostalloftherespondentsagreed(85%)orstrong-lyagreed(12%)thatitistheirresponsibilitytodiscussadherencewithadolescents.Thefollowingquotationhighlights the importance of a team approach to ad-dressing adherence:

It’sateameffort.Initially,themoremedical-lytrainedstaff(MDsandRNs)shouldspeak

Figure 2. Percentage of adolescent transplant recipients providers believe struggle with adherence

Figure 3. Factors providers believe contribute to nonadherence

23


tothepatientandfamilyregardingmedica-tions,whattheydotohelptheirbody,andhow important it is to take them. Then, otherstaff(ChildLife,Psychology,SocialWork,etc)cangetinvolvedtobuildrap-portandprovidecontinuedsupportaroundwhyit’sdifficulttoadhere,problem-solving,therapeuticinterventions,etc.

Inresponsetoanopen-endedprompttodescribetheirfrustrationswithadolescentnonadherence,providersidentifiedtheriskofrejection,death,orpreventable loss of the donor organ and need for re-transplant;lackofparentalabilitytoappropriatelysupervise adherence and provide support; lack of adolescent insight into the risks; lack of honesty; and difficultieseducatingadolescentsandtheirfamiliesandmotivatingthemtowardsbetteradherenceby“gettingthemtoseethebiggerpicture.”Providersfo-cusedontheseverityofconsequencestononadher-ence, and used strong words to express these conse-quences,suchas“wasteofapreciousresource(theorgan),”“rejectionofthepreciousorgan,”“knowingthiscouldbeadeathsentence,”and“theyarewast-ingapreciousgift!”Furthermore,theconsequencesofnonadherencewerenotedtoaffectnotjusttheteen’shealth,buttheiremotionalwell-beingandthepeople around them, including their family members andthestaff.

Improving AdherenceFurtheropen-endedresponseshighlightedthat2providersacknowedgedfrustrationsinthewaytheirteamshandleadherence,indicatingthattherearestepsthestaffcouldtaketoimproveadherenceofpatients.Oneparticipantstated,“Ithinkwefailtosupportthemenoughandmakeourselvesavailable.”Anotherparticipantnotedthefollowing:

For us not to learn from teens who don’t succeed and then be able to apply those lessons to the next person. I think we tend toputeveryoneinthesame‘pot’andsaythey’re just all teens. I believe there are somespecificsthatcanbelookedat.

Providersofferedseveralsuggestionstoimproveadherenceintheiropen-endedresponses,includingaspectrumofpre-andpost-transplantinterventionsand“anorganizedteamapproach.”Theyoutlinedideasforeducationondiseaseandencouragingin-

creased autonomy, parent involvement, and support from transplant team members. They recommended ongoing monitoring and individualized treatment tailoredforthespecificreason(s)fornonadherenceandcognitivedevelopment,andtheyhighlightedtheimportanceofprovidingemotionalsupportandofferingmentalhealthtreatment.Othersuggestionsincludedbehavioralinterventions,suchasschedulesandroutines,reinforcementandrewards,motivation-al interviewing, and problem solving. Two important themes emerged from providers’ sug-gestionsregardinghowtoimproveadherence.First,theprovidersemphasizedthecriticalroleofpeersupport. For example, they suggested peer support couldbefacilitatedbyofferingateensupportgroup,utilizingpeerrolemodels,orhavingateenspeakerdiscusshowheorsherequiredare-transplantduetononadherence. This was evidenced by ideas such as: • “Peer support groups with other transplant

survivors”• “Teensupportgroupcounseling”• “Support groups, help seeing that this chronic

illness is part of them but shouldn’t stop them fromdoingeverythingtheywantto(includingbeingnormal)”

• “Learningfromotherteenswhohavefailedtransplantsfromnonaderence”

Second,thenoveluseoftechnology(phones,com-puters,apps,socialmedia)wasidentifiedasapoten-tialmediumforinterventions,withsuggestionssuchas: • “Easyreminders(cellphonealarms,texts)”• “Contemporary methods to remind them—text

orsocialmediabasedremindersystem”• “Maybe something tech related that would be

easy to use and something that could easily inte-grate on their phones/computers to assist them toremember”

• “Monitoringdevicesthattellushowoftentheyopentheirpillbottle”

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Discussion

Assessment of Adherence Thefindingthatprovidersbelievemostoftheirado-lescentpatientsstrugglewithadherenceisconsistentwith the literature and is also reassuring given previ-ousfindingsthatproviderstendtooverestimatethelevelsofadherenceoftheirpatients.37 Providers re-portedtheyfrequentlyaskaboutadherence,thoughtheyremainskepticalaboutadolescents’honestyre-gardingadherence.Thisskepticismiswarrantedgivenresearchthatadolescentstendtoover-reporttheiradherence.10Additionally,responsestoopen-endedquestionsclearlyindicatedthatnonadherenceelicitsstrong feelings in providers of transplant recipients. Providerperspectivesofadolescentadherenceandthesignificantamountoftimeandresourcesdedi-cated to addressing adherence were consistent across provider type and the 3 organ transplant teams, sug-gestingthatadherenceisacriticallyimportantissueregardless of provider or organ type.Providers highlighted the importance of ongoing monitoring of adherence, which aligns with research indicatingthatpre-andpost-transplantscreening,monitoring,prevention,andearlyinterventionsetthe stage for success.15 Adherence measures such astheAdolescentandParentMedicationBarriersScales,16 the Medical Adherence Measure,38 and the Basel Assessment of Adherence with Immunosup-pressiveMedicationScale(BAASIS)39 can be useful in elicitingaccurateandtruthfulreportsofadherence,particularlyinconjunctionwithimmunosuppressivelaboratoryassaysandcollateralinformationfromthemedicalteam.Literaturesuggeststhatcollectingdatafrommultiplesourcesofinformationismoresensitivetodetectingnonadherencethan1methodaloneandprovidescomparableestimatestoelectronicmonitor-ing,suchastheMedicationEventMonitoringSystemthattrackseachtimeapillbottleisopened.40 Providersindicatedthatbehavioralandemotionalfac-tors,familyfactors,andrelationshipwithtransplantteamareassociatedwithadherenceintheirpatients,which is consistent with prior literature and high-lightstargetsforintervention.7Increasedattentiontopatient-relatedfactorsthatmaycontributetonon-adherenceinthispopulationshouldbeincorporatedintostandardizedinquiriesaboutadherence.Specificquestionsaboutthefollowingwouldbehelpfulto

includeinaclinicalvisit:(1)individualfactors(eg,forgetfulness,emotionalorbehavioralproblems,de-velopment,andlackofinsight),(2)familyfactors(eg,conflictorlackofsupervision),and(3)socialandpeerfactors.Socio-economicfactors(eg,healthliteracy)andhealth-carefactors(eg,needformoresupportfrom team, need for increased availability of providers toaddressadherence)werealsoidentifiedandcouldbeeasilyincorporatedintoassessmentduringapost-transplantfollow-upclinicvisit.Athoroughassess-mentofnonadherenceisthefirststepindefiningtheproblembeforeimplementinginterventions.

Interventions for NonadherenceImprovingadherenceisateameffort,butitcanbefrustratingforproviders,especiallygiventhesever-ityoftheconsequencesofnonadherence.Provideropen-endedresponsesemphasizedtheemotionalimpact adolescent nonadherence has on providers. Indeed, the responses to this survey indicate that providersremaindedicatednotonlytothewell-beingofthepatientandfamily,butalsototheethicsofprotectingthedonatedorganinthecontextofdonororgan shortages. Providersofferedthoughtfulsuggestionsforaddress-ingthesecontributingfactorsinwaysthatcanbetailoredtotheneedsandpreferencesofeachpatient,includingeducation,mentalhealthtreatment,andindividual and group social support for parents and adolescents.Theirsuggestionsalignwiththeresearchsupportingmulticomponentinterventionsdesignedtoaddresstheuniquepredictorsofandbarrierstoadherence in adolescents.23,30-31 Individual behavioral interventionsformedicationadherenceutilizeself-monitoring,behavioralmodification,andproblem-solving to address barriers to adherence, such as peer acceptanceconcerns.Evidence-basedtreatments(eg,Cognitive-BehavioralTherapy,InterpersonalTherapy,AcceptanceandCommitmentTherapy,DialecticalBehavioralTherapy)addressmentalhealthproblems,such as Major Depressive Disorder, which can nega-tivelyimpactadherence.Providers highlighted the importance of family su-pervision of care and monitoring of adolescent medication-taking(eg,verifyingthatamedicinewastaken,ensuringthatapill-boxisstoredinaconve-nientlocation);thesestrategiesshouldbeencouragedto improve adherence.41Additionally,familyinter-

25


ventionshelpparentsimplementpositivereinforce-mentforadherencebehaviors,decreaseproblematicinteractionsthatmayserveasbarriers,andincreasestructureandroutinearoundmedication-taking.41 In pediatric transplant, as like other chronic medical con-ditions,familymembersmaybenefitfromreferralsfor their own mental health treatment or from peer/groupsupport,especiallyiftheyhaveinadequatesocial support.42

Advancing the Standard of Care Resultsoftheprovidersurveyandexistingliteratureemphasizes that adherence must be assessed in the context of the various systems that impact adherence. Building on the results of this survey, our transplant psychology team has worked to enhance adherence services available to the children and families treated atthischildren’shospital.Toimproveidentificationand assessment of adherence, we have implemented routinescreening,includingutilizationoftheParentandAdolescentMedicationBarriersScale.16 For ex-ample,intheKidneyCenter,wehavebegunmeetingwiththemultidisciplinaryteampriortoeachclinictoaddress psychosocial concerns and monitor the stan-darddeviationofthelast5immunosuppressantlevelstotargetpatientsthatwouldbenefitfrompsychologyinvolvement at clinic visits. Though adolescent group treatment has not histori-callybeenoffered,notonlyhavetheprovidersiden-tifiedteenpeersupportasaneed,butthefamilieshavealsoidentifiedthisneedintheirclinicvisits.Onesignificantchallengetohostingateengroupisthesignificantdistancethatmostofourpatientsmusttravel to the hospital, with the majority of our families residinggreaterthan100milesaway.Manypatientscompletetheirlabsandfollow-upcarewiththeirprimary care physicians. However, individual, family, or group behavioral health services, especially that aresensitivetouniquetransplantissues,arescarceoutsidemetroareas.Providersemphasizedtheutilityoftechnologicalinterventionswithadolescenttrans-plantrecipients,whichcouldutilizeindividualandgroup telehealth treatment. Currently, Transplant Psy-chologyisimplementingandinvestigatingtheaccept-ability,feasibility,andeffectivenessofa5-sessionado-lescentadherencegroupinterventiondeliveredviatelehealth. Technology and telehealth could expand individualandgroupserviceswithpatients,parents,

orsiblingstoofferthefullspectrumoffamily-cen-teredservicesandincreaseaccesstoevidence-basedcare at this pediatric transplant center.

Limitations and Future DirectionsThisprojecthasmethodologicallimitations,includingasmallsamplesize,participationoftransplantteamsat a single hospital, and lack of a rigorous survey designprocessorpilottest.Tomovefromqualityimprovement to research that generates generaliz-able knowledge, future studies should survey teams atmultiplehospitalsandconductamoreformalpilottestingofthesurvey.Thiswouldincreasethesurvey sample size and diversity, which would allow researcherstoexploremorenuancedrelationships,suchasdifferencesbetweenprovidersororgantypeacrossdifferenttransplantteamswithvariouslevelsof exposure to behavioral health assessment and intervention.Whilethisprojectincludedprovidersof heart, liver, and kidney transplant teams, future surveyprojectscouldincludeinformationfrompro-vidersofothersolidorganortissuetransplantpro-grams,suchaslung,multivisceraltransplant,andothermulti-organtransplants.Providerperspectivescouldalsobecomparedtopatientandcaregiverperspectivestoenhanceourunderstandingofad-herence across contexts as well as to clinical data such as immunosuppressant laboratory values, and clinicaloutcomes.Whilemanypatient-andfamily-relatedfactorsofadherencewereidentifiedinthisprojectasavenuesforfurtherintervention,fewoftheotherWorldHealthOrganization’sriskandpro-tectivefactors(Figure1)wereidentifiedincludingalackofmentionofsocio-economic,condition-related,therapy-related,andhealth-carefactors.Patientsandfamiliesmaybebettersuitedthanproviderstoiden-tifysuchfactors.Despitetheselimitations,thisqualityimprovement project provides important guideposts for improving the transplant psychology service and multidisciplinarypsychosocialcareatourhospitalandultimatelytheoutcomesoftheadolescentpatientswe serve.

26


Table 1.Timespentdiscussingadherenceandproviderperspectivesonadherencebyproviderandorgantype

Provider Type Organ TypeTransplant Coordina-tors&Physicians

Other Team Members Abdominal Heart

Mean % of Clinic Vis-its Spent Discussing Adherence

24 27 27 20

Mean % of Teens Pro-viders Think Struggle w/Adherence

69 64 67 66

Appendix

Adolescent Transplant Adherence: Provider SurveyThankyoufortakingthetimetocompletethisbriefsurvey.Wehopetolearnmoreaboutyourperspectivesonadher-enceinadolescenttransplantpatients.Pleasekeepinmindtheadolescenttransplantpatientsthatyouprovideclinicalcaretowhenyouanswerthefollowingquestions:

1. ProviderType(checkone)a. Transplant Coordinatorb. MD–Surgeonc. MD–TransplantAttendingd. MD–OtherTransplantTeamPhysiciane. MD–ResidentorFellowf. AdvancedPracticeProvider(non-transplantcoordinator)g. RN(non-transplantcoordinator)h. Social Workeri. Pharmacistj. Dietitiank. Psychologyl. ChildLifeSpecialistm. Other:

2. TransplantPopulationthatyouworkwith(checkallthatapply)a. Liverb. Kidneyc. Heart

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3. Whatfactorsdoyouthinkcontributetononadherenceinadolescenttransplantpatients?(checkallthat apply)

a. Forgetting/poorplanningb. Emotionalproblemsc. Behavioral problemsd. Cognitiveproblemse. Economic problemsf. Parentalemotionaldistressg. Familyconflicth. Perceivedinjusticeordesiretobenormali. Sense of immortalityj. Peer acceptancek. Body imagel. SideEffectsm. IngestionIssues(eg,Inabilitytoswallowmedications,badtaste)n. Need for autonomyo. Poor monitoring by parentsp. Runningoutofmedicationsq. Other:

4. Howfrequentlydoyouaskaboutmedicationadherenceinyourinteractionswithteenagepatients?a. VeryFrequentlyb. Frequentlyc. Occasionallyd. Rarelye. Very Rarelyf. Never

5. Whatpercentageofyourclinicvisitsorinteractionswithteensdoyouspendfocusedondiscussingadherence?(fillinthenumber)___%

6. Whatpercentageofadolescenttransplantrecipientsstrugglewithadherence?___%

7. Howoftentoyouthinkyouradolescentpatientsarebeingtruthfulabouttheiradherence?a. VeryFrequentlyb. Frequentlyc. Occasionallyd. Rarelye. Very Rarelyf. Never

8. Ibelieveitismyresponsibilitytodiscussadherencewithmyadolescentpatients.a. Strongly Agreeb. Agreec. Undecidedd. Disagreee. Strongly Disagree

9. Whoseresponsibilityisitontheteamtodiscussadherence?

10. Whatareyourbiggestfrustrationswithnonadherentteens?

11. Whatkindofhelpdoyouthinkteensneedtoimproveadherence?

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5. RodrigueJ,NelsonD,HantoD,ReedA,CurryM.Patient-reportedimmunosuppressionnonadherence6to24monthsafterlivertransplant:Associationwithpretransplantpsychosocialfactorsandperceptionsofhealthstatuschange.Prog Transplant.2013;23(4):319-328.

6. Williams PG, Holmbeck GN, Greenley RN. Adolescent health psychology. J Consult Clin Psychol.2002;70(3):828-842.7. DobbelsF,VanDamme-LombaertR,VanhaeckeJ,DeGeestS.Growingpains:Non-adherencewiththeimmunosuppressiveregimeninado-

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2003;7(6):489-493.12. PaiAL,DrotarD.Treatmentadherenceimpact:Thesystematicassessmentandquantificationoftheimpactoftreatmentadherenceon

pediatric medical and psychological outcomes. J Pediatr Psychol.2010;35(4):383-393.13. DiMatteoMR,LepperHS,CroghanTW.Depressionisariskfactorfornoncompliancewithmedicaltreatment:Meta-analysisoftheeffectsof

anxietyanddepressiononpatientadherence.Arch Intern Med.2000;160(14):2101–2107.14. NevinsTE.Non-complianceanditsmanagementinteenagers.Pediatr Transplant.2002;6(6):475-479.15. RianthavornP,EttengerRB.Medicationnon-adherenceintheadolescentrenaltransplantrecipient:Aclinician’sviewpoint.Pediatr Trans-

plant.2005;9(3):398-407.16. SimonsLE,BlountRL.Identifyingbarrierstomedicationadherenceinadolescenttransplantrecipients.J Pediatr Psychol.2007;32(7):831-

844.17. LeeJL,EatonC,Gutiérrez-ColinaAM,etal.Longitudinalstabilityofspecificbarrierstomedicationadherence.J Pediatr Psychol.

2014;39(7):667-676.18. McCormickKingMLM,MeeLL,Gutiérrez-ColinaAM,EatonCK,LeeJL,BlountRL.Emotionalfunctioning,barriers,andmedicationadherence

in pediatric transplant recipients. J Pediatr Psychol.2014;39(3):283-293.19. ShemeshE,AnnunziatoRA,ShneiderBL,etal.Improvingadherencetomedicationsinpediatriclivertransplantrecipients.Pediatr Trans-

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33. O’GradyJGM,etal.Multidisciplinaryinsightsintooptimizingadherenceaftersolidorgantransplantation.Transplantation.2010;89(5):627-632.

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Regression, Depression, and Psychosis in Down Syndrome Case Report

Regression, Depression, and Psychosis in a Young Adult Female with Down Syndrome: A Case Report

Introduction

There have been previous reports in the litera-ture of adolescents and young adults with Down

syndrome(DS)experiencingsignificantbehavioralandcognitiveregressionofunclearetiology.ThesepresentationshavevariouslybeenreferredtoasDownsyndromedisintegrativedisorder,devel-opmental regression, depression, and catatonia inDownsyndrome.YMwasa21-year-oldfemalewithDownsyndromepresentingwithlossofskillsandlanguage,responsetointernalstimulirelatedto a popular television show, and slowed motor movementsafteramajorlifestressor.Herwork-upincluded laboratory assessments; neuroimaging studies;andconsultationsbydevelopmentalpediat-rics,neurology,andpulmonology.Withnoidentifiedmedical cause of her decline, she was referred to psychiatry and started on sertraline and risperidone. Afewmonthsafterstartingpsychiatricmedication,she began weekly individual psychotherapy. Within 18monthsofstartingtreatment,shewasfunc-tioningatherpreviousbaseline,withnoresidualsymptoms.Unexpectedly,2yearsaftertheonsetofinitialsymptoms,YMexperiencedasecondregres-sion. The precipitant for this decline was not appar-ent,andshenolongerrespondedtomedicationand therapy. However, she returned to her baseline functioningafterapproximately12sessionsofelec-troconvulsivetherapy(ECT).YM’scaseisdifferentfrom many of those previously published, as she was highfunctioningandarticulatepriortoherregres-sions. Because of her verbal skills, she was able to offersomeinsightintoherinternalexperience.Herrelapsefollowingcompleteresolutionofsymptomsisanotherdistinguishingcharacteristicofherclini-

cal course. YM’s history underscores the challenges in developing a protocol to address developmental regressioninDSasthevariationinsymptomsandcontributingfactorsnecessitateanindividualizedtreatment plan.Downsyndrome(DS)isthemostcommongeneticdisorderintheUnitedStates,presentinapproxi-mately 1 in 691 live births.1 Individuals with DS are knowntoexhibitdifferentbehavioralandpsychiatricphenotypes across the lifespan. Younger individu-alsexhibitmoreaggressionanddefiance,whereasadolescents and adults tend towards internalizing symptoms, including social withdrawal and depres-sion.2Inarecentevaluationofpsychiatricdiagno-ses among adolescents and young adults with DS comparedtootherintellectualdisabilities,individu-alswithDSweremorelikelytoexperiencepsychoticand depressive symptoms than their counterparts.3 There are reports in the literature of young adults with DS experiencing developmental regression, butnotallofthemappeartofitintothebroaderdefinitionsofdepressionandpsychosis.Literatureon this topic is sparse, primarily case reports about 1 or a few individuals. There are overlapping symp-toms present in the majority of cases such as motor slowness,facialgrimacingortics,increasedself-talkand social withdrawal, and lack of spontaneous expressivelanguageproduction.4Presentationvari-abilityhasresultedincasesbeingdefineddifferentlyamongproviders(Downsyndromedisintegrativedisorder,5 developmental regression,6 depression,7 orcatatonia).8Thesedifferentconceptualizationsmaycontributetoconflictingratesofreportedpsy-chopathology amongst individuals with DS and

Lina Patel, PsyD; Elise M. Sannar, MD*

*Author Affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine, Pediatric Mental Health Institute, Children’s Hospital Colorado.

31

Patel, Sannar

evolvingunderstandingofcontributingfactorsinregression.DuetotheknownassociationofDSanddevelop-mentofneurofibrillaryplaques,regressionhasbeenhypothesizedasanearlymanifestationofAlzheimer’sdisease(AD).Symptomsthatmaypredatethedevel-opmentofdementiaincludesadness,sleepproblems,and general regressive behavior.9 In their report of acute neuropsychiatric disorders in adolescents with DS, Akahoshi et al found that when compared with adults with DS without regression, neuropathologi-calchangescharacteristicofADwerepresentear-lier.10 There is also a case report in the literature of an adolescent boy with DS and regression success-fullytreatedwithdonepezil,amedicationtradition-allyusedtotreatAD,incombinationwithanSSRI.However, most episodes of regression in children and adolescents resolve completely with treatment, which would not be expected if the regression were a precursortodementia.Medical factors such as autoimmunity, hormonal shifts,andexposuretoanesthesiamayplayaroleinthe development of regression. Worley et al report on a series of 11 children and adolescents seen over a10-yearperiodwithregression.Theysuggestanewterm,“Downsyndromedisintegrativedisorder,”tode-scribethephenomenaofautisticregression,cognitivedecline, and insomnia seen in their case sample. They notethatDownsyndromedisintegrativedisorderisdifferentfromatypicalautisticregressioninchildrenwith DS based on age of onset, female predominance, andassociatedinsomnia.Themajorityofpatientsintheirsample(91%)alsoshowedelevatedthyroperoxi-daseantibodytiterscomparedto23%ofage-matchedcontrols with DS without regression. Based on this finding,theysuggestthatDownsyndromedisintegra-tivedisordermaybelinkedtoautoimmunity.5 The on-set of menarche has been noted in a number of cases asaprecipitanttoregression.However,resolutionofhormonal imbalances alone has not resulted in return tobaselinefunctioning.Exposurestosurgicalstresscausingneuroinflammationandanesthesiacausingthe depression of cholinergic transmission have also been postulated as risk factors for regression.4

The majority of cases in the literature implicate life stressorsascontributingtoregression.Forexample,Steinetalreviewedthecaseofa13-year-oldfemalewith DS, developmental regression, and depression.

Her decline occurred in the context of moving homes and changing classrooms. They propose that behav-ioralproblemscouldbeaformofcommunicationinan individual with minimal expressive language. This patientwasalsodiagnosedwithobstructivesleepap-nea and her regression coincided with menarche. She exhibitedimprovementwithacombinationofantide-pressantmedication,continuouspositiveairwaypres-sure for her sleep apnea, and increased psychosocial supports.6 Other noted life stressors in the literature include a death in the family, change in living environ-ment,changeinfamilyconstellation,anddifferentworkand/orschoolexpectations.4

Ghaziuddin et al described the histories of 4 adoles-centswithsignificantsymptomsofregressionwithoutclearmedicaletiology.Ineachofthecases,regres-sion was characterized as catatonia, manifested by changeinmotoractivity(reducedorlessoftenin-creasedmotoractivity),unusualmovements(stereo-typies,grimacing,freezing,ambitendency,infrequentblinking,motororvocaltics,posturing,automaticobedience),changesinspeech(reducedmeaning-fulspeech;mutism;echolalia;“verbigeration,”orsenselessrepetitionofwordsandphrases;increasedlatency),changesinoralintake(reducedappetiteand/orslowingdownoffoodintake),declineinactivi-tiesofdailyliving,bladderorbowelincontinence,negativism,anddisruptionsincognition.Someofthecases also had symptoms of depression and psycho-sis,butnonerespondedsignificantlytoantidepres-santorantipsychotictreatment,andinoneindividual,therewasconcernthatsuchmedicationsmadethingsworse.8Inaseparatecasereport,GhaziuddinandJapreported on 2 other cases of adolescent females with DS and catatonia.12Allofthecasesfromthe2articlesshowed symptom improvement with either benzodi-azepines and/or electroconvulsive therapy.

Case History

First RegressionYMwasa21-year-oldfemalewithDownsyndrome,previouslyconsideredhighfunctioning,urgentlyreferredforpsychiatricevaluationduetoa4-monthepisodeofcognitiveandbehavioralregression,in-cluding loss of language, slowed motor movements, internalpreoccupation,andconcernforpsychosis.ThesesymptomsdevelopedafterYMmovedaway

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fromhometoattendaspecialout-of-statecollegeprogram for individuals with developmental disabili-tiesinthefallof2013.Priortoherregression,YMwasdescribedas“extremelysharpandquick.”Shewasindependentlymotivatedtoengagesociallyandman-ageinteractionsonherownandhadneverrequiredmental health care. When she returned home for Thanksgiving break in 2013,YM’sparentsnoticedsomeminordeclinesinherfunctioning.Shewaslessengaged,andmumbledandlaughedtoherselfmoreoften.However,herparentsfeltshewas“okay,”despitesomeworryaboutthischangeinherpresentation.Theirconcernsabat-edsomewhatafterspeakingtostaffatthecollege.ByDecember2013,YMexhibitedasignificantdeclineinfunctioning.Shebarelyrespondedtoorengagedininteractionsandconversation.Shewas“inherownworld,”frequentlylaughingtoherself.Sheregressedin her ability to communicate, could not coherently formulate her thoughts, and struggled to manage all activitiesofdailyliving.Additionally,sheexperiencedasignificantincreaseinself-talkandsocialwithdraw-al.Herself-talkrevolvedaroundatelevisionshowforyoung adults involving popularity, murder, conspiracy, anddeception.Sheidentifiedherselfasacharacterinthe show and struggled to separate herself from the reality she created. Facial grimacing and nasal snort-ingwerenoted,inadditiontoslowedmovements.Laterintreatmentwhenthinkingaboutherinitialregression, YM stated, “In the middle of the day my brainistoofoggy,soIhavetomakeaface.”InJanuary2014,YM’sparentscontactedahospital-based clinic for individuals with Down syndrome ask-ingforanevaluationoftheirdaughter’sregression.YM’s primary care physician had examined her and, unable to uncover a medical cause of her symptoms, referredherforadditionalassessment.AttheDownsyndrome clinic, a developmental pediatrician evalu-atedher.YMwasunabletosocializeandattunementtoherenvironmentsufferedgreatly.Duringthesession, between long periods of blanking out, YM describedherthinkingas“fuzzy.”Shevaguelyarticu-lated feeling stressed and overwhelmed at college. Her parents had been unaware of the level of her dis-tress,butknewthatshewasspendingalotoftimeonhomework,hadminimalsocializationwithherpeers,and forgot to eat most days. She spent all of her extra timewatchingapopulartelevisionshowforyoung

adults.Laboratorytestswereorderedwhich,otherthanaslightlylowferritinlevel,werewithinnormallimits. The pediatrician started YM on sertraline, a selectiveserotoninreuptakeinhibitor.Melatoninwasalso introduced to help with ongoing sleep issues. Her parents were instructed to keep her engaged and to avoid any exposure to the television show on which shewasfixated.YMinitiallyshowedminorimprove-ments.However,afterabout6weeksofsertralinetreatment she started to deteriorate. She developed abnormal movements and was more socially with-drawn and internally preoccupied. Due to her lack of sustained improvement, YM was referred for mental health services.YMhadahistoryofobstructivesleepapnea,diag-nosed years earlier. She had a tonsillectomy and adenoidectomy at age 6 and repair of a submucosal cleftatage12.Continuouspositiveairwaypressuretreatment(CPAP)wasrecommendedin2009.Shewascompliantwiththeinterventionforafewyears,butthen stopped, complaining that it was uncomfortable and that the air leaked into her eyes. YM’s parents also said her sleep symptoms, such as snoring, had resolved, thus she had not used CPAP for 2 years prior toher2013declineinfunction.HerfamilynotedamajorchangeinYM’ssleeppatternswhenshere-turned from college in December 2013. She took hourstofallasleepduetoconstantself-talk,wokeupseveraltimesduringthenight,andneededhelpfromher mother to fall back asleep. Melatonin was help-ful in managing sleep issues, but a repeat sleep study showedcontinuedsymptomsofobstructivesleepapnea.Duetotheimpactofobstructivesleepapneaoncognitivefunction,CPAPcompliancebecameakeytreatment goal.13 Oninitialevaluationwithpsychiatry,YMrespondedminimallytodirectquestioning.Sheappeareddi-shevelled and internally preoccupied, evidenced by slumpedposture,mattedhair,andfoodstainsonherclothes. She was moving her lips as if talking to herself whileavertinghergaze.YMwasorientedtonameandplace,butnottime.Onoccasion,shegiggledinappro-priately. Her mother explained that she was running episodes of a popular television show through her head and that she believed she was one of the char-acters. She cooperated with having her vital signs checked,butwalkedslowlybacktotheoffice.Sheexhibited abnormal physical movements including

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scrunchingherface,sniffingdramatically,lookingup,and pushing out her lips. Becauseoftheconcernthatshedeterioratedafterher dose was increased, the psychiatrist decreased YM’ssertraline.Risperidone,asecondgenerationantipsychoticmedication,wasaddedtargetingpsy-chosis.Basedonpresentingconcerns,thetimelineofdeterioration,andthelackofobviousmedicaletiol-ogy for her symptoms, YM was diagnosed with an unspecifieddepressivedisorderwithpsychoticfea-tures. Symptoms of depression included low mood, socialwithdrawal,lackofinterestandmotivation,decreasedappetite,andpoorsleep.Symptomsofpsy-chosisincludedinternalpreoccupationandbeliefthatshe was a character in a television program. YM also metdiagnosticcriteriaforcatatonia,butthisdiagno-siswasonlyconsideredafterdoingaliteraturereviewforcaseswithsimilarpresentations.Aftershowingsomeslightimprovementswithmedication,YMbe-ganindividualtherapy.DuetoYM’ssignificantperiodsof blanking out with no response or ability to follow theconversation,sessionswerelimitedto30minutesonce per week. Appointments targeted increasing engagement and strategies for tracking conversa-tions.Sheparticipatedinmultiplecommunityactivi-tiesandtherapiesforindividualswithdevelopmentaldisabilities.Priortoherregression,YMneverneededinvolvement with disability services, so this was a new area for her and her family to navigate. The family had adifficulttimekeepingYMengagedathome.Useofawrittenschedule,journaling,andscheduledbreaksforself-talkweresuggested.Attheonsetoftherapy,YM gave generic responses to make it seem like she wasfollowingtheconversation.Intherapy,shewastaughthowtorequesthelporclarificationwhensheblankedoutorherthinkingbecame“foggy.”Although YM showed improvement with psychiatric interventionandresumptionofCPAP,becauseoftheseverityofherpresentingsymptoms,additionalmedi-calwork-upwassuggested.ThisincludedanMRIandEEG,bothofwhichwerenormal.Afterafewmonthsofmedicationandpsychotherapyintervention,YMself-reported,“I’mbecomingmyselfagain.”Shewasable to engage in meaningful back and forth conversa-tionandwaslessinternallypreoccupied.Overtime,YM was more able to advocate for herself.AsYM’sabilitytofollowconversationsandanswerdirectquestionsimproved,psychotherapysessions

focused on addressing distorted thinking and using strategiesforremainingpresent-focused.Evenearlyon,duringmomentsofclarity,YMwasabletoself-reflectthroughart.Indescribingoneofherpaintingsshe said, “I feel kind of dark inside. The past mistakes arecomingoutnow.”Appointmentscontinuedweek-ly,butthedurationincreasedtoanhour.YM’slevelofinsightincreasedexponentially.Despitetheimprove-ments in her regression and psychosis, she looked more depressed. She stated, “There is a lightness and brightness in my brain and forehead combined with thefogginess.Itispainfultothink.”Hersertralinewasincreasedtargeting“mentalfogginess”asamanifes-tationofdepression.InMarch2015,taperingofherrisperidonewasinitiatedduetosideeffectsofweightgainandsedation.YM was eventually able to engage in discussion about her distorted thought process and depressive symptoms.Shearticulatedadesiretobemorelikethe main characters in the television show that had preoccupiedher,whoarebeautiful,thin,andpopular.Themesofperfectionwerealsonoted.YMsharedthatdespitewantingtobelikemanyofthecharactersintheshow,sherelatedmosttoadifferentcharacterwho she perceived as being bullied and rejected. Over time,YM’simprovementsallowedhertoarticulatethe internal struggles she experienced when moving away from home. She felt she had to rely on herself, ratherthanfindingsupportfromfriendsandfamily.She stated, “When you are in a new town or a new place, you kind of feel invisible. It is hard to be inde-pendentwithoutyourfamily.”YM’sfamilysharedin-sightintosmallchangesinhermotivationtointeract,herabilitytofocusonthecontentofcommunications,andherhumor.Priortoherinitialregression,YMwasdescribedasfunnyandengaging.There-emergenceof these traits served as a barometer of her improve-ment.YMwasbetterabletoidentifywhenshewasengagedinhertelevision-basedinternalnarrative,which allowed for more accurate assessment of im-provementanddeclineinfunctioning.

Second RegressionInmid-November2015,YM’sfamilybegannoticingsomeminordifferencesinherbehavior.Sheforgottodothingslikeshuttingthecardoorafterexiting,losthertrainofthoughtduringconversations,andhadbrief moments of withdrawing into her own world.

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Over a period of 2 weeks, YM’s periods of withdrawal increasedsignificantlyandsheneededpromptingforallactivitiesofdailyliving.Shecouldnotdressherselfwithoutsupport,experiencedadecreaseinappetiteandenergy,andstruggledtofollowsimplesingle-stepdirections.Shewasunabletowritehernameorstateherlastname.Directquestioningresultedinincon-gruent responses. For example, when asked how she slept the night before, she responded, “There were 5.”Hermotherspeculatedthatshewasagainrunningepisodes of the television show through her mind and was responding to the scenes. Her mother later dis-covered that YM had watched part of an episode on November 21st, 2015, just before her second regres-sion.Medicaletiologieswereagaininvestigated,buttherewasnoidentifiedexplanationforherdeterioration.Symptoms remained consistent with depression and psychosis.Inaddition,YMmetdiagnosticcriteriaforunspecifiedcatatonia.Overthenext3months,adjust-ments to her sertraline and risperidone did not result insignificantimprovement.Thepatientattendedtherapy appointments twice per week with the goal of keeping her engaged and grounded in reality. In contrast to her previous psychotherapy treatment, shestruggledtoparticipateinameaningfulway.Shecouldanswer1or2concretequestions,butthenwouldbegintoself-talkloudlywithoutanyacknowl-edgementorrecognitionofthetherapistbeinginthe room. She laughed to herself and made bizarre statements.Interjectionintotheconversationbythetherapistdidnotresultinself-awarenessorchangein behaviour. Despite having come to therapy in the samelocationforoverayear,YMoftenbecamecon-fused about where she was going and the risk of YM wanderingoffbecameproblematic.Hersymptomswere tracked closely, but she showed no improve-ment. The psychiatrist added low dose lorazepam for insomnia with slight improvements. Due to her historyofobstructivesleepapnea,shewasbrieflymedicallyadmittedforpulmonarymonitoringduringatrialoflorazepamupto11mgdailytargetingcatato-nia.Hersertralineandrisperidonewerediscontinued.Although she tolerated the lorazepam medically, she was more confused and less verbally responsive to directinteraction.Thepsychiatristtaperedheroffthelorazepam and started a course of electroconvulsive therapy(ECT).

After4ECTtreatments,YMshowedmomentsoflucidity.Inbiweeklytherapysessions,shewasbetterabletotracktheconversationandansweredafewmorequestions.Improvementswerenotedonthemini mental status exam, but she was only able to focusforamaximumof30minutes.After30minutes,YMwouldoftenasktogototherestroom.Thethera-pist and YM’s mother would hear her loudly talking to herself in the restroom. The content remained bizarre innature,butYMwasabletore-engageintherapyfora short period once she returned from the bathroom. Even when she was aware that others had heard her self-talk,shewasnotabletodiscussitfurther.Hersymptomsofregressionresolvedcompletelyafter12ECTtreatments(3timesweekly),andshefunctionedatherpre-regressionbaseline.Withthemoreabruptresolutionofhersymptoms,YMwasonlyabletore-flectonherregressionasrelayedbyfamilymembersand providers. She started maintenance ECT and was treated with low dose lithium carbonate based on her history of mood symptoms. YM does not recall any details of her regression and refers to it as her “sick-ness.”Shehasadifficulttimeunderstandingwhathappenedandhasexpressedsadnessaboutthetimethat she lost and the many events she missed out on whileshewasill.Sheoftenmentionsthateveryone“movedonwiththeirlives”withouther.

DiscussionWithin the last 10 to 20 years, there has been in-creased focus on regression in Down syndrome. Variousetiologichypotheseshavebeennotedintheliterature, including autoimmune phenomenon and psychosocial stressors. In the case of YM, the distance fromprevioussupportandscaffolding,increasedacademicexpectations,andhighinternaldrivetosucceedinanewsettingresultedinsocialwithdrawal,disruptionofsleeppatterns,poorhygieneandfoodintake,andobsessivethoughtsaboutperfection.Initially,YM’sdisconnectionfromrealitypreventedher from sharing the intricacies of her college experi-ence.Cognitive-behavioraltherapyinconjunctionwithmedicationmanagementallowedhertodevelopinsight into how this experience was overwhelming. Despitethisinsight,YM’sinternaldriveforself-reli-ance and independence likely contributed to her re-lapse.Hercaseoffersinsightintoregressiontriggered

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by psychosocial stressors at a level not previously discussed within the literature.YM’sinitialresponsetopsychiatricmedicationiscon-sistentwithmanyreportedcases.Mostpatientsshowimprovementwithsomecombinationofantidepres-santandantipsychoticmedication.Forpatientswhodonotrespondtomedicationsandwhomeetdiag-nosticcriteriaforcatatonia,moreintensiveinterven-tion,suchashigh-dosebenzodiazepinesorECT,mayberequired.ItisnotunderstoodwhyYMinitiallyhadcompleteresolutionofhersymptomswithmedica-tion,onlytorelapse.Consistentwithothercasere-ports,YMimprovedwithECTafterfailingmedicationinterventions.8

Findingsfromthiscasestudysupportamultimodalapproach to addressing regression in Down syndrome. Psychiatricmedication;therapy;andintensive,ac-tiveinvolvementincommunityactivitiesresultedinaninitialreturntobaselinefunctioningforYM.YM’ssecondregressionwasnottriggeredbyanidentifiable

psychosocial stressor and the treatments that had beeneffectiveforthefirstregressionprovedineffec-tive,requiringtheintroductionofnewtherapeuticapproaches(eg,electroconvulsivetherapy).Shehasagainshowncompleteresolutionofsymptomswiththis new approach. Some professionals in the Down syndromecommunityhavereportedmultipleregres-sions in an individual, but there is no literature to describe this phenomenon.14 Review of the literature supports an individualized approach for assessment andinterventioninsimilarcases,assymptomoverlapdoes not guarantee the same response to treatment. WhileregressioninDownsyndromecontinuestobepoorly understood, YM’s case illustrates the need forfrequentevaluationoffunctioningduringtimesoftransitionandpotentiallyincreasedstress.Atthistimethereisnoprotocoltopreventregressiveepi-sodes,butimprovedidentificationanddescriptioncouldleadtodevelopmentofpreventivestrategies.

References

1. ParkerSE,MaiCT,CanfieldMSetal.UpdatednationalbirthprevalenceestimatesforselectedbirthdefectsintheUnitedStates,2004-2006.Birth Defects Res A Clin Mol Teratol.2010Dec;88(122):1008-16.

2. DykensEM,ShahB,SagunJ,BeckT,KingBH.MaladaptivebehaviorinchildrenandadolescentswithDown’ssyndrome.J Intell Disabil Res. 2002;46(6):484-492.

3. DykensEM,ShahB,DavisB,BakerC,FifeT,FitzpatrickJ.PsychiatricdisordersinadolescentsandyoungadultswithDownsyndromeandotherintellectualdisabilities.J Neurodev Disord. 2015;7:9.

4. DevennyD,MatthewsA.Regression:atypicallossofattainedfunctioninginchildrenandadolescentswithDownsyndrome.Int Rev Res Dev Disabil.2011:41:233-264.

5. WorleyG,CrissmanBG,CadoganE,MillesonC,AdkinsDW,KishnaniPS.Downsyndromedisintegrativedisorder:new-onsetautisticregres-sion,dementia,andinsomniainolderchildrenandadolescentswithDownsyndrome.J Child Neurol.2014:1-6.

6. SteinDS,MunirKM,KarweckAJ,DavidsonEJ,SteinMT.Developmentalregression,depression,andpsychosocialstressinanadolescentwith Down syndrome. J Dev Behav Pediatr,2013;34;216-218.

7. WalkerJC,DosenA,BuitelaarJK,JanzingJGE.DepressioninDownsyndrome:areviewoftheliterature.ResDevDisabil.2011;32:1432-1440.8. GhaziuddinN,NassiriA,MilesJH.CatatoniainDownsyndrome;atreatablecauseofregression.Neuropsychiatr Dis Treat.2015;11:941-949.9. Zigman WB. Atypical aging in Down syndrome. Dev Disabil Res Rev.2013;18:51-67.10. AkahoshiK,MatsudaH,HanaokaT,SuzukiY.AcuteneuropsychiatricdisordersinadolescentsandyoungadultswithDownsyndrome:Japa-

nese case reports. Neuropsychiatr Dis Treat.2012;8:339-354.11. TamasakiA,SaitoY,UedaRetal.EffectsofdonepezilandserotoninreuptakeinhibitoronacuteregressionduringadolescenceinDown

syndrome. Brain Dev.2016;38(1):113-117.12. GhaziuddinN,JapSN.CatatoniaamongadolescentswithDownsyndrome:areviewand2casereports.JECT.2011;27:334-337.13. BreslinJ,SpanoG,BootzinRetal.ObstructivesleepapneasyndromeandcognitioninDownsyndrome.Dev Med Child Neurol. 2014;56

(7):657-664.14. D.McGuire,personalcommunication,December2,2015.

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Comorbid Neurodevelopmental and Medical Diagnoses Case Report

AMultidisciplinaryApproachtotheTreatmentofComorbid Neurodevelopmental and Medical Problems

Case Presentation

Jackisa10-year-oldboywithahistoryoflyeinges-tionat18months,whichresultedinesophagealstenosis, vocal cord paresis and dysphagia, aspi-rationsyndrome,andjejunostomytube(J-tube)placement. He had regular swallow studies over theyearssubsequenttohisingestion,andstartedfeeding therapy with a speech and language thera-pistatage10whileJ-tubedependent.Jackhadattendedoutpatientpsychotherapyforangerandbehavioralconcernsfortheyearpriortopresentingfor current treatment. A pediatrician had prescribed astimulantmedicationforsymptomsofattentiondeficithyperactivitydisorder(ADHD)sinceage5.Oneyearbeforethetimeofevaluation,thepedia-tricianhaddiscontinuedmethylphenidateduetoweight loss, which became a primary health con-cern as his low BMI placed him in failure to thrive range(BMI<1st%ile).Inadditiontohismedicalrisk,Jackdemonstratedsignificantimpairmentsacrossphysical,social,psychological,andschoolfunction-ing, which prompted a referral to the Medical Day Treatment(MDT)programbyhispediatrician.TheMDT program is a partnership between a children’s hospital and school district to provide classrooms utilizingthedistrict’scurriculumwithinatreatmentsettinghousedinthebehavioralhealthsectionofachildren’s hospital. The program’s services include a nursing team to provide medical supervision and dailymedicalcare,teachingstafffromtheschooldistrict, and a mental health team including psycho-therapists(licensedclinicalsocialworker,clinicalpsychologist,andpostdoctoralpsychologyfellow),milieusupportstaff,andaconsultingpsychiatrist.Atthetimeofenrollment,Jackwasnotcompleting

hisJ-tubefeedsathomebecauseitwasdifficultforhis mother to manage his refusal behaviors, which wereassociatedwithfearsthathisJ-tubewoulddisconnect in the middle of the night, since that occurredinthepast.Jackhadcompletedfourthgradeandhadanindividualizededucationprogram(IEP),whichincludedspeechtherapy,occupationaltherapy, reading services, and psychological support. Jackpresentedtotheintakewiththepriordiagno-sisofADHD(notedabove),aswellassymptomsofdepression(sadness,irritability,frequentcrying)andanxiety(fears,worries,separationanxiety).HismotherstatedJackalsoexhibitedfrequentanger,irritability,andschoolrefusalbehaviors(eg,cryingeverymorning).Shedescribedhimashavinglong-standingdifficultieswithpeers,includingnoiden-tifiedfriendsandexperiencingincreasedteasingovertheprioryear.Jacklivedwithhismotherand3siblings(16-year-oldsisterand12-year-oldtwinsisters,oneofwhomwasseverelydisabled).Jack’s12-year-oldsisterhadseverephysicalimpairmentsduetocerebralpalsy,whichrequiredconstantcareby his mother. His mother was unemployed and had nooutsidesupportfromherfamily.Jack’smotheralsoreportedherownhistoryoflearningdisabilitiesand mental health problems.Duringtheinitialevaluation,Jack,whowashold-ingastuffedanimal,appearedhighlyanxiousanddid not verbally respond to the interviewer. When he did verbally respond, his answers did not match thequestionorcontentoftheinterviewandheexpressedworrieshewouldcontinuetobeteasedat MDT. His responses to the Revised Child Anxiety andDepressionScale(RCADS)1,2suggestedclinically-significantlevelsofseparationanxiety,generalized

Harpreet Kaur, PhD; Monique Germone, PhD; Marissa Schiel, MD, PhD; Emily Edlynn, PhD*

*Author Affiliations: Phoenix Children’s Hospital, Phoenix, AZ (Dr Kaur); and Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine, Pediatric Mental Health Institute, Children’s Hospital Colorado (Drs Germone, Schiel, and Edlynn).

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Kaur, Germone, Schiel, Edlynn

anxiety,panic,socialphobia,anddepression(refertoTable1forresults).Basedonthereasonsfortheinitialreferralandre-sults of our assessment, treatment goals focused on improving caloric intake, addressing anxiety and de-pression,improvingpeerrelationships,anddecreas-ing impulsivity in the classroom. The psychotherapist coordinated with the nursing team to address barriers to increasing caloric intake and weight gain. The team developed a system to track progress by implement-ingweigh-instwiceaweekanddocumentingthepercentage of food intake at breakfast and lunch. The teamrecommendedchangingthetimingofJ-tubefeeds to the evening with video games to address his fearofovernightfeeds,andJackcooperatedwiththisnewschedule.Afixed-ratioreinforcementscheduleimplemented in the program and at home included rewarding increased food intake in order to build morepositiveassociationswiththeeatingexperi-ence.3,4ThisbehavioralapproachalsotargetedJack’sfearofchokingthroughexposureandrelaxationtrain-ing.Athome,Jackearnedmarblesinajarwhenhecompleted his feeds and then exchanged the marbles foravideogame.Duringthistime,thepsychothera-pistprovidededucationtoJack’smother,thenursingteam, mental health counselors, and teachers regard-ingeffectivebehavior-managementtechniques,suchascontingencymanagementanduseofpositiverein-forcement.5Jackwasalsotaughtemotion-regulationskills to decrease tearfulness and tantrums during mealtimesandfeeds.Finally,collaborationwiththepediatricianresultedintheutilizationofhomenurs-ing support in order to facilitate consistent feeds at homeandprovidegreatersupporttoJack’smother.6 PriortoadmissiontoMDT,Jackhadbeenprescribedmethylphenidate(patchandliquidformulations)startingaroundage5yearsold.Hehadstoppedtak-ingthestimulantmedicationapproximately1yearpriortopresentingtoMDT,duetoconcernsbyhispediatricianaboutlowappetiteandweightloss.However,feedingdifficultiesdidnotresolvewithdiscontinuationofthestimulantandhedidnotgainweight.Jack’sfirstpsychiatricevaluationoccurredwithin 1 month of admission to MDT. Weight con-cerns(BMI<1st%)andareportedinabilitytoswallowpillsdictatedinitialmedicationchoices.Stimulantswerenotanoptionandatomoxetinedoesnotcomeinliquidformulation.Givenconcernsaboutboth

anxietyandpoorfoodintake,thefirstpsychiatristrec-ommended low dose dispersible olanzapine 2.5 mg atbedtimeandmotherprovidedconsent.Althougholanzapineisnotconsideredfirst-linetreatmentforanxietyanddoesnothaveanindicationforfeedingdisorders in children, mother reported that olanzap-inewasbeneficialforanxiety,sleep,andweight.Itispossible that improvements in symptoms could have resultedfromeitherhisparticipationintheprogramorstartofmedication,oracombinationofboth.WhiletherewasimprovementinJack’semotionregulation,hecontinuedtodemonstrateunusualbehaviorssuchasrepeatingthesamerandomwordinresponsetoallquestionsandrespondingtosocialcuesinappropriately(eg,laughinginresponsetohispeers’expressionsofsadness).Hestruggledtode-velopappropriatepeerrelationships,exhibitedcom-municationdifficulties,andcontinuedtodemonstratefoodrefusalbehaviorsandearlysatiety,leadingtonoimprovement in his BMI. To evaluate if these concerns could be related to a possible developmental disorder, JackwasreferredforanAutismSpectrumDisorder(ASD)evaluation.Thisevaluationincludedtheadmin-istrationoftheSocialCommunicationQuestionnaire,Lifetime(SCQ)7; the Social Responsiveness Scale, SecondEdition(SRS-2)8;andtheAutismDiagnosticObservationSchedule,SecondEdition,Module2(ADOS-2)9; as well as a developmental history inter-viewwiththemother,andaclassroomobservationofthepatient.ResponsesontheSRS-28 indicated perceived severe deficienciesinreciprocalsocialbehaviorthatresultedin moderate interference in everyday social interac-tions(TotalScore,T-score:75).Suchscoresaretypicalfor children with a diagnosis of an ASD of moderate severity.ResponsesontheSCQ7indicatedsignificantperceiveddifficultiesinsocialcommunicationthatwere also consistent with a diagnosis of an ASD. The administrationoftheADOS-2wasmodifiedonthebasis of his language level and developmental age. BasedonthestandardizedprotocoloftheADOS-2,hewasadministeredModule2(PhraseSpeech)insteadofModule3(FluentSpeech,Child/Adolescent).HedisplayedseveralcommunicativestrengthsduringtheADOS-2administration,includingtheuseofcommu-nicativegestures(eg,pointing)andresponsetotheexaminer’squestions.Hisareasofweaknessincludeddifficultyinitiatingandmaintainingaconversation

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(ie,conversationoccurredonlywhenhewasaskedaquestionanddidnotelaborate),anoticeablelackofeye contact, few social overtures, and communica-tionmostlytorequestitemsorassistancefromtheexaminer.NorestrictedandrepetitivebehaviorswereobservedduringtheADOS-2administration,however,handflappingandrepetitivefingermovementswerenotedduringtheclassroomobservation.Jack’soverallTotalscoreontheADOS-2Module2algorithm for children aged 5 years or older was consistentwithanADOS-2Classificationofautism(specificADOS-2scoresarenotreportedasperthemanualizedrecommendationsoftheADOS-2).HisADOS-2ComparisonScorefurtherindicatedthatontheADOS-2,hedisplayedamoderatelevelofautismspectrum-relatedsymptomsascomparedwiththosewhoareclassifiedashavingASDontheADOS-2andare of the same chronological age and language level. Basedonthesefindings,cognitivebehavioralinter-ventionsweremodifiedtoaddresssocialandcommu-nicationdeficitsassociatedwithautism.10 Toaddressdepressionandanxiety,Jackparticipatedinroleplaysabouthowtoeffectivelyexpresshisemotions.Hewasintroducedtostep-by-stepemo-tionregulationstrategiestousewhenbecomingdysregulated, and visual cues were placed throughout his classroom to remind him to use these strategies. AndwhileJackshowedmoderateprogressinemotionidentificationandexpression,hestruggledwithapply-ing his skills learned in therapy to the classroom due toimpulsivityandinattention.Giventhis,apsychiatricevaluationwasrequested.JackwasevaluatedbythenewMDTpsychiatristcon-sultant for ongoing concerns about ADHD symptoms as evidenced by the teacher Vanderbilt11results(inat-tentionandhyperactivityboth9/9).Atthetime,Jackcontinuedtotakeolanzapinedispersibletablets.ThepsychiatristdiscussedtreatmentoptionsforADHDwith both mother and the pediatrician, who support-edtheuseofeitheranalpha2agonistorastimulantgiventhatJack’sweightcouldbecloselymonitoredintheprogram.Thepatientwasstartedonguanfacine,whichwastitratedslowlyto0.5mgtwiceadayovera2-monthperiod(theinitialtitrationwasslowbecauseitwasunknownifJackwouldbeconsistentlyabletoswallowpills,butheultimatelywasabletoswallow

themedicationwithoutdifficulty).Vanderbiltassess-ments suggested some improvement in ADHD symp-toms,thoughtheycontinuedtobeinthediagnosticrangeforADHD.(Teacherscores-inattention6/9andhyperactivity7/9,andparentscores-inattention2/9andhyperactivity6/9.)GuanfacinewaschangedtoaslowreleaseversionguanfacineSR(1mg)toimprovecoverage.AfterthechangetoguanfacineSR1mg,Jack’smothernotedamoremarkedimprovementinsymptoms, including increased focus and decreased hyperactivity.Jack’spsychotherapistalsoreportedbenefits,includingJack’simprovedabilitytorespondtoredirectionandincreasedparticipationinprogramactivities.Jackhadabreakinmedicationmanagementduetoaninsuranceinterruptionthatimpactedaccesstopsychiatricservicesbilledtoinsurance,butnotJack’senrollmentintheMDTprogram*.Duringthistime,thefamilywasunabletoobtainhismedicationsforabout 1 month; guanfacine SR and olanzapine were thereforediscontinuedandJack’ssleepandbehaviorsworsened.Onceinsurancewasre-instated,motherconsentedtorestarting1medicationatatime,begin-ningwithguanfacineSR1mgdaily.Jack’smotherreportedthatJack’slisteningabilitiesimprovedandherespondedwelltoredirection.Olanzapinewasnotrestarted since anxiety had decreased and there was noclearindicationforthemedication.In individual psychotherapy, behavioral strategies such aspracticingimpulsecontrolandregulatingemotion-alresponseswereusedtosupportthepositiveeffectsofmedication.Jackshowedanimprovedresponsetolearningskills,andnewbehavioralrecommendationswere made both to the teacher to implement in the classroom, and to his mother to implement in the home.12,13Theserecommendationsfocusedontheuseofpraise,simplifyingexpectationsintosmallstepsusingvisualcues,andreducingdistractions.AlthoughJack’semotionalandbehavioralfunctioningimprovedwiththeseinterventions,hecontinuedtostrugglewithgainingweight.Jack’spsychotherapistreportedconcernsaboutJack’scontinuedweightlossandmother’sabilitytoensureJackwasconsum-ingsufficientcaloriesathometotheDepartmentofSocialServices(DSS).DSSassignedacarecoordinatortoworkinthehomeandtoassistJack’smotherwith

*MDT receives funding from the state budget and does not receive direct reiumburesment from Medicaid; this allows for MDT services to continue during a temporary disruption in insurance coverage.

39


navigatingthehealthcaresystem.PriortoDSSinvolve-ment,Jack’smothercommunicatedwiththetreat-ment team about her own mental health challenges, whichseemedtointerferewithimplementingbehav-ioralapproachesinthehomeandlimitthepatient’sweightgain.AfterDSSbecameinvolved,motherbe-gan her own mental health treatment. The treatment teamcontinuedtoworkwiththeDSScoordinator,whoregularlyattendedtreatmentmeetingswiththemother. The coordinator served as a bridge between theprogramandhome,andwasabletohelpJack’smotherfollowtherecommendationsmadebytheteam.Asaresult,Jack’smotherwasabletoimple-mentrecommendationsmadebytheteam,includingbehavioral strategies to manage problem behaviors during feeds.ThismultidisciplinaryteamapproachtoassessmentandtreatmentyieldedsubstantialimprovementsacrossareasofJack’sfunctioning:school,social,emo-tional,behavioral,andhealth.Thepatientpresentedto the treatment program with concerns related to schoolrefusal,failuretogainweight,socialrelation-ships,andemotionalandbehavioralsymptoms.Jack’sschoolrefusalbehaviorsimmediatelyextinguished,with98%attendanceinthetreatmentprogramdur-ing the school year and over the course of 2 summer programs. His mother reported that he showed no refusalbehaviorsorseparationanxiety,gettingreadyinthemorningswithhighcooperationandnoneedforencouragement.Jackalsorespondedwelltoafixedratioreinforcementscheduleimplementedtoincrease medical adherence. His food intake on the unitincreasedfromone-quarterofbreakfastandone-halfoflunchtoone-thirdofbreakfastandthree-quar-ters of his lunch, and he consistently drank his meal supplement twice a day without challenging behav-iors.Jack’sBMIincreasedfrom13.1(<1st%)atintaketo14.4(2nd%)at15months;thisindicatedaweightincrease of 11 pounds. Notably, his BMI peaked at 15.2(12th%)atalmost6monthsintotreatmentandweightfluctuationshavebeendocumentedoverthecourse of his 15 months of care.The RCADS1,2andthePedsQualityofLife(PedsQL)14 were administered at intake and at the end of the school semesters to assess symptoms and monitor treatmentoutcomes(at7and15monthspostintake).ThePedsQLFamilyImpactModule(PedsQLFIM),15 a validatedmeasureofparentandfamilyfunctioning,

wasnotpartoftheintakeassessmentbattery,butwasusedatothertimepointsduringtreatmenttoassessparentandfamilyfunctioning.Overall,theseresultsindicatedthatJackhadasignificantdecreasein anxiety and depression from the clinical range at intake to the normal range in most domains 7 months later, with improvement sustained at 15 months. Jack’sfunctioningandqualityoflifealsoappearedtosubstantiallyimproveacrossareas,with15-65pointincreasesforself-report,and9-100pointincreasesforparent-report(theparentratedherchildasa0foremotionalandschoolfunctioningatintake;sheratedhimat100forthesesameareas15monthslater).ResultsonthePedsQLsubstantiateobservationsofimprovementsemotionally,socially,andinschool.ScoresonthePedsQLFIMalsoindicatedimprovedparentandfamilyfunctioningacrossallbut1areabetween 7 months and 15 months. Please see Table 1 for further details.

DiscussionChildrenwithfeedingdifficultiesoftenstruggletomaintain a healthy weight. Feeding disorders, includ-ingavoidancerestrictivefoodintakedisorders,arecommon in children diagnosed with neurodevelop-mental disorders, but they can also develop as a result of environmental or biological factors.16Theexistingliteraturesuggestsusingpsychiatricmedications,posi-tivereinforcement,andcognitivebehavioraltherapyforchildrenwhohavedevelopedfeedingdifficultiesafteramedically-traumaticevent.Distractionandexposuretechniquesarerecommendedforchildrenwithanorganiccausetotheirfeedingdifficulties.4 A comprehensiveandeffectivetreatmentplanisessen-tialintreatingfeedingdisorders,sincechronicfeedingdifficultiescanleadtosuboptimalgrowth,socialdefi-cits,nutrientdeficiencies,andpooracademicprog-ress.6 Although the literature provides this guidance forfeedingdisorders,Jackshowedminimalresponsetotheseinterventions,indicatingamorecomplicateddiagnosticpresentation.Indeed,Jackdemonstratedbothorganic(dysphagiaandaspiration)andbehavior-al(failuretothrive)aspectstohisfeedingdisorderinthe context of other serious medical, psychiatric, and psychosocial challenges, underscoring the need for a multidisciplinaryapproachtotreatment.Jack’streatmentcoursehighlightshowvaluableathoroughassessmentprocesscanbeinidentifying

40


factorsthatwerepreviouslynotidentifiedorad-dressedinstandardapproachestotreatingfeedingdisorders.Jackhadparticipatedinmultipleinterven-tionsandevaluationsthroughschoolpriortohisenrollment at Medical Day Treatment, however, his ASDremainedundiagnosed.InformationfromJack’sASDevaluationhelpedshapeinterventionstargetingtreatmentgoalstodevelopage-appropriatesocialskills,managepeerrelationships,andimprovefeedingbehaviors.Jack’sdevelopmentallevelandcognitive,social,andemotionalskillswereusedtosetrealisticgoalsintreatment,andtheyweremodifiedbasedonJack’sreadinessandabilitytolearnanewskillorbehavior.Jackmaynothavedemonstratedtreatmentgainsifthetreatmentinterventionswerenotmodi-fiedbasedonhisdiagnosesanddevelopmentallevel.Providers should consider comprehensive medical andpsychologicalevaluationandre-considerinter-ventionsusedinsessionsifsymptomspersistafterparticipationinevidence-basedtreatments.Jack’spsychiatriccomorbiditiesbecameacentralfo-cusofhismultidisciplinarytreatmentandareworthyof further discussion. ASD is a neurodevelopmental disorderaffectingapproximately1%ofthepopula-tionandisoftencomorbidwithfeedingproblems.17 Behaviors associated with feeding disorders and ASD, includingfoodrefusalandavoidance,canhavesignifi-cantnegativeimpactsonthechild’shealthandtheparent-childrelationship.Thesebehaviorsinchildrenwith ASD may be the result of sensory, behavioral, or social impairments and are treated with behavioral interventions.6OneofthekeybehavioralinfluencesofASDonfeedingdifficultiesmaybesymptomsofrepetitiveness,rituals,andhyper-orhyposensitiv-ity to sensory input aspects of the disorder. Children diagnosedwithASDmayhavespecificritualsassoci-atedwithmealpreparationandmealtimes.Addition-ally, children diagnosed with ASD have higher rates ofgastrointestinaldistress,whichmayplayarolein the development of feeding problems. However, therelationshipbetweenfeeding,ASD,andmedicaldiagnoses have not been parsed out in the literature. Sincethisisthecase,amultidisciplinaryapproachtotreatment, at a developmentally appropriate level, is criticallyimportant.6

Inaddition,ADHDandanxietyarehighlycomorbidwith ASD,18 adding complexity to psychiatric and behavioralsymptompresentationforachildwith

feedingdifficulties.ChildrenwithcomorbidADHDand ASD demonstrate higher rates of problems with inhibitionandgreaterseverityofASDsymptomsthan children with ASD alone.19, 20 The comorbidity of medicalandneurodevelopmentalconditionsrequirescarefulevaluationandcoordinationacrossproviderstooptimizetherapeuticinterventions.InJack’scase,ADHD treatment had been limited by concerns of weightlossandfeeding/swallowingdifficultiesthatinitiallylimitedmedicationchoices.Psychostimulantsassociatedwithanincreasedriskofappetitesuppres-sion in children with ASD, similar to the rate in typi-cally developing children.21 A recent study reported thatextendedreleaseguanfacinewasefficaciousfordecreasinghyperactivityandimpulsivityinchildrenwithASD,suggestingitisareasonablealternativetostimulantsinchildrenwithADHD,ASD,andfeed-ing problems.22Indeed,thiscaseillustratednegativeoutcomes of untreated ADHD, including a decline inbehavioralfunctioningthatnegativelyimpactedacademicandsocialfunctioning.TheadditionofmedicationtotargetADHDsymptomsofimpulsivityandinattentionthatdidnotsuppressJack’sappetiteallowed the treatment team to implement behavioral andcognitivebehavioralstrategiestoaddressothermedical and psychological symptoms. Identificationofbarrierstotreatmentandimplemen-tationofaplantoaddressbarrierstotreatmentisasimportantasanytherapeuticinterventionincomplexpediatric cases,10andthemultilidisicplinaryteam’sabilitytoaddressthechallengesinJack’shomeenvi-ronmentwereparticularlycriticalforhistreatment.WhileDSSinvolvementisoftenresistedbyfamiliesduetonegativemisperceptionsandfeelingsofdisem-powerment,itwascriticallyimportanttoaddressingthechallengesJack’smotherfacedinmanaginghiscomplex medical and psychiatric problems.23 Feeding difficultiescanbeasubstantialburdenforfamilies,especiallyinsinglecaregiverhomeswithmultiplechil-dren with special health care needs. Providers should becomefamiliarwiththeorganizationsandservicesavailable to families and use those resources to help bridgethegapbetweenofficeandhome.Thiscasealsoexemplifiestheimportanceofusingarangeofmethods to evaluate progress and outcomes, includ-ingscoresfromvalidatedmeasures,observationaldata,andobjectivemetrics.

41


ConclusionJack’ssuccessfultreatmentinvolvedtheuseofmul-tipleinterventionmodalities,theworkofaskilledmultidisciplinaryteam,andthedevelopmentofasystemofcare.Alsocriticalwasthesustaineden-gagementofthisteamandsystemovera15-monthperiod, which was necessary to realize meaningful progress.Thiscollaborationofmedicalcare,psycho-logicaltreatment,psychiatricconsultation,familysup-port, schools, and community resources models the idealapproachtoapatientsufferingfrommedical,emotional,academic,social,behavioral,andfamilial

challenges.Eachinterventionmayhavehadsomesuccessinisolation,butitislikelythattheircom-binationresultedinsynergisticeffects,andgreaterand more sustained improvements than would have been achievable with a less integrated approach. The MedicalDayTreatmentmodelisuniquelycapableofthecoordinated,multidisciplinaryapproachtoassess-mentandongoingtreatmentthatpatientslikeJackdesperately need if they are to move from pervasive functionaldeficitstothrivingacrossdomainsoffunc-tioningessentialtooptimaldevelopmentandpositiveoutcomes.

Table 1.Psychologicaloutcomemeasureresultsovertime

Intake 7 Months 15 MonthsParent Self Parent Self Parent Self

RCADSGeneralized Anxiety

70 74 51 49 35 45

Panic 51 73 41 50 45 55Social Anxiety 75 84 43 45 35 47SeparationAnxiety

>80 78 >80 79 65 59

Depression >80 84 69 66 72 50PedsQLPhysical 91 59 100 75 100 75Emotional 0 40 50 55 100 60Social 25 35 90 65 100 50School 0 20 70 70 100 85Total 37 41.3 80.4 67.4 100 68.5PedsQLFamilyImpactPhysical N/A 42 75Social N/A 6.25 37.5Emotional N/A 60 100Cognitive N/A 45 10Communica-tion

N/A 25 50

Worry N/A 55 85Total N/A 36.81 53.47

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References

1. ChorpitaB,MoffittC,GrayJ.PsychometricpropertiesoftheRevisedChildAnxietyandDepressionScaleinaclinicalsample.Behav Res Ther. 2005;43(3):309-322.

2. EbesutaniC,BernsteinA,NakamuraB,ChorpitaB,WeiszJ.ApsychometricanalysisoftheRevisedChildAnxietyandDepressionScale—Par-ent Version in a clinical sample. J Abnorm Child Psychol.2009;38(2):249-260.

3. LinscheidTR.Behavioraltreatmentsforpediatricfeedingdisorders.Behav Modif.2006;30(1):6-23.4. 4.KerznerBetal.Apracticalapproachtoclassifyingandmanagingfeedingdifficulties.Pediatrics.2015;135(2)344-353.5. SilvermanAH,TarbellS.Feedingandvomitingproblemsinpediatricpopulations.InM.C.RobertsMC,SteeleRGeds,Handbook of Pediatric

Psychology.4thed.NewYork:GuilfordPress;2009:429-445.6. VissokerRE,LatzerY,Gal,E.EatingandfeedingproblemsandgastrointestinaldysfunctioninAutismSpectrumDisorders.Res Autism Spectr

Disord.2015;12:10-21.7. RutterM,.BaileyAB,LordC.Social Communication Questionnaire. Torrance, CA: Western Psychological Services; 2003.8. ConstantinoJN.Social Responsiveness Scale,SecondEdition.Torrance,CA:WesternPsychologicalServices;2012.9. LordC,RutterM,DiLavorePC,RisiS,GothamK,BishopSL.Autism Diagnostic Observation Schedule,SecondEdition.Torrance,CA:Western

Psychological Services; 2012.10. NationalAutismCenter.Findings and conclusions: National standards project, phase 2;2015Randolph,MA:NationalAutismCenterhttp://

www.nationalautismcenter.org/national-standards-project/phase-2/.11. WolrachML,LambertW,Doffing,MA,BickmanL,SimmonsT,WorleyK.PsychometricpropertiesoftheVanderbiltADHDDiagnosticParent

RatingScaleinareferredpopulation.J Pediatr Psychol.2013;28(8):559-568.12. Kazdin AE. Parent management training: evidence, outcomes, and issues. J Am AChild Adolesc Psychiatry.1997;36(10):1349-56.13. PelhamW,Burrows-MacLeanL,GnagyEetal.Transdermalmethylphenidate,behavioral,andcombinedtreatmentforchildrenWithADHD.

Exp Clin Psychopharmacol.2005;13(2):111-126.14. VarniJ,SeidM,RodeC.ThePedsQL™:MeasurementModelforthePediatricQualityofLifeInventory.Medical Care.1999;37(2):126-139.15. VarniJW,ShermanSA,BurwinkleTM,DickinsonPE,DixonP.ThePedsQLTMFamilyImpactModule:Preliminaryreliabilityandvalidity.

Health Qual Life Outcomes, 2. 2004:55.16. MillerC.Updatesonpediatricfeedingandswallowingproblems.Curr Opin in Otolaryngol Head Neck Surg. 2009:1.17. AssociationA.Diagnostic And Statistical Manual Of Mental Disorders,FifthEdition(DSM-5®).Washington,D.C.:AmericanPsychiatricPub-

lishing; 2013.18. SimonoffE,PicklesA,CharmanT,ChandlerS,Loucas,T,BairG.PsychiatricdisordersinchildrenwithAutismSpectrumDisorders:Preva-

lence,comorbidity,andassociatedfactorsinapopulation-derivedsample.J Am Acad Child Adolesc Psychiatry.2008;47(8):921-929.19. MannionA,LeaderG.Comorbidityinautismspectrumdisorders:Aliteraturereview.Res Autism Spectr Disord.2013;7:1595-1616.20. SprengerLetal.ImpactofADHDsymptomsonautismspectrumdisordersymptomseverity.Res Dev Disabil.2013;34:3545-3552.21. ReichowB,VolkmarFR,BlochMH.SystematicReviewandMeta-AnalysisofPharmacologicalTreatmentoftheSymptomsofAttention-

Deficit/HyperactivityDisorderinChildrenwithPervasiveDevelopmentalDisorders.Journal of autism and developmental disorders. 2013;43(10):2435-2441.

22. ScahillLetal.Extended-ReleaseGuanfacineforhyperactivityinchildrenwithautismspectrumdisorder.Am J Psychiatry. 2015 Dec 1;172(12):1197-206.

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Twohy, Malmberg, Williams

AComprehensiveTransdiagnosticApproachto Pediatric Behavioral Health

In this paper, a transdiagnostic approach to assess-mentandinterventionisproposedasamethodto

comprehensively address the complex behavioral health needs of individual children and adoles-cents. The term transdiagnostic is not yet widely understoodinthefieldofpsychotherapyresearch.Itisbestdefinedasanapproachthat“drawsfromaunifyingtheoreticalmodelthatexplainsdispa-rateconditionsviacommonmechanisms.”1 Here, the term transdiagnostic will be used to describe a clinical approach that reduces reliance on diagnos-ticcategoriesfortreatmentplanning.Rather,theproposedapproachtotransdiagnostictreatmentis guided by a targeted assessment of the underly-ingmechanismsthatdriveandmaintainidentifiedbehavioral,emotional,andsocialconcerns.

Atransdiagnosticapproachtobehavioralhealthmaybeparticularlyusefulinaddressingtherealityofcomplex,highlycomorbidclinicalpresentations.Lifetimeprevalenceestimatesindicatethatapproxi-mately half of those who meet criteria for a psy-chiatric disorder will also meet criteria for at least 1 other disorder, with most comorbid presenta-tionshavinganonsetinchildhoodoradolescence.2 Researchers have made considerable progress in thedevelopmentofevidence-based,transdiagnos-tictreatmentsforcomorbidpresentationsinadultpopulations(eg,Barlow’sUnifiedProtocolfortheTransdiagnosticTreatmentofEmotionalDisorders).3 Amongpediatricpopulations,theabilitytoconcur-rentlytreatcomorbidpresentationsisarguablyevenmorecritical,givenhighratesofpsychiatric

Eileen Twohy, PhD; Jessica Malmberg, PhD; Jason Williams, PsyD*

AbstractAtransdiagnosticapproachtochildren’sbehavioralhealthtreatment“drawsfromaunifyingtheoreticalmodelthatexplainsdisparateconditionsviacommonunderlyingmechanisms.”1Transdiagnosticbehavioralhealthinterventionshavegainedincreasingattentionfortheirpotentialtobetteraddresstherealityofcomplex,highly-comorbiddiagnosticpresentationsandenhancethedisseminationandimplementationofevidence-basedpractices.Whilesignificantgainshavebeenmadeintheadult-focusedtransdiagnosticliterature,furtherdelineationofapediatrictransdiagnosticapproachiswarranted.Thispaperhighlightskeytransdiagnosticmechanisms that have been associated with both internalizing and externalizing pediatric behavioral health problems(eg,parenting,sleepregulation,emotionregulation,informationprocessingbiases,andexperientialavoidance),andreviewsthecurrentstateoftheliteratureontransdiagnosticassessmentandintervention.Initialeffortstodevelopandimplementanewtransdiagnosticclinicalprogramdesignedtomoreeffectivelyaddressthebehavioralhealthneedsofchildrenandadolescents,improvethedisseminationandimplementa-tionofevidence-basedtreatments,andaddresskeyweaknessesinthepediatrictransdiagnosticliteraturearethendescribed.Thefirststageoftheprogramhasfocusedondevelopingtoolstoefficientlyandeffectivelymeasuretransdiagnosticmechanismsthatunderliepediatricbehavioralhealth,whichwillthenguidecliniciansin developing a modularized treatment plan that is individually tailored. This approach holds great promise in furtherelucidatingthetransdiagnosticmechanismsthatunderliepediatricbehavioralhealthproblemsandtheireffectivetreatment.Furthermore,theseapproachesmayinformthedevelopmentofamoretargetedclassificationsystemforbehavioralhealthproblemsandimprovecurrentassessmentprocedures.

Author Affiliations: Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine, Pediatric Mental Health Institute, Children’s Hospital Colorado.

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Transdiagnostic Pediatric Behavioral Health Services

comorbiditiesanddevelopmentalcontinuityacrossthe lifespan. Results from a longitudinal community study of children ages 9 to 16 revealed considerable concurrentcomorbidity,with25.5%ofchildrenidenti-fiedashavingpsychiatriccomorbidities.Forexample,the odds of having an anxiety disorder among chil-drenwhohadadepressivedisorderwere25.1timeshigher for boys and 28.4 for girls when compared to children without a depressive disorder. And the odds ofhavingoppositionaldefiantdisorderamongboysandgirlswhohadadepressivedisorderrelativetothose without a depressive disorder were 20.7 and 15.1,respectively.4Interestingly,heterotypiccontinu-ity(continuityfromonediagnosistoanother)wasmuch stronger in girls than boys. For example, girls with anxiety were shown to be at higher risk for later development of substance use disorders.4 In order toeffectivelytreatandmaintaintherapeuticgains,clinicians must be able to diagnose and treat a child’s primarypresentingproblem,aswellasanycomorbidconcerns. For example, a child referred for concerns relatedtodisruptivebehaviormayalsodemonstrateanxious avoidance, depressive symptoms, and/or sleepdysregulation.Ifthesecomorbidconcernsarenot addressed, treatment outcomes will likely be poor andshort-lived.The present paper argues that a comprehensive trans-diagnosticapproachtopediatricbehavioralhealthwouldbetteraddressthecomplexneedsofchildren,adolescents, and their families, while also providing opportunitiestofurtherinvestigateandunderstandthemechanismsthatunderlieemotionalandbehav-ioraldifficulties.Limitationstocurrentclassificationandtreatmentpracticeswillbediscussed,followedby a review of the state of the research on transdi-agnosticapproachestopediatricbehavioralhealth.Necessaryfutureresearchdirectionswillbeintro-duced,includingtheneedtoimprovetransdiagnosticassessmentmethodsandtoexpandtransdiagnosticinterventionapproachestoincludeexternalizingaswellasinternalizingpresentations.Finally,currentpi-lot projects designed to address the measurement of transdiagnosticmechanismswillbedescribed.Theseprojects have focused on developing assessment tools(eg,semi-structuredinterview,parentandchildquestionnaires)aimedatefficientlyandeffectivelymeasuringpertinenttransdiagnosticmechanismsas-sociated with pediatric behavioral health.

Limitations to Current Classification and Treatment PracticesThelimitationsofthecurrentdiagnosticsystemforpsychiatricdisorders(ie,DiagnosticandStatisticalManualofMentalDisorders,FifthEdition;DSM-5)5 areoftendiscussed.Alongstandingtensionexistswithin this system, in which the need for a common and reliable language competes with the reality of complex,highlycomorbidclinicalpresentations.2 Interventionresearchbasedonthecategoricalap-proach to diagnosis, as delineated in the DSM, has resultedinevidence-basedtreatments(EBTs)devel-opedforthoseindividualswithclear,single-diagnosisclinicalpresentations.Unfortunately,thesemanual-izedtreatmentsmaybelesseffectiveforthemanypatientswhomeetcriteriaformultipleDSMdiag-noses or experience subclinical impairment across multipleareas.6Further,manualizationoftreatmentsforspecificdisordersleadstotraininganddissemina-tionchallenges.ItisnotrealistictoexpectindividualclinicianstoattaincompetencyinallavailableEBTs,norisitcosteffectiveforclinicstotrainstaffonthegrowingnumberofdiagnosis-specificinterventions.7 Thistrainingburdenisparticularlytroublesomeinlightofevidencethat,despitepositivefindingsinhighly-controlledefficacytrials,EBTsforyoutharenotnecessarilymoreeffectivethanusualcareinreal-worldpracticesettings.8 RecentdiscussionsinthefieldofpsychotherapyimplementationhavearguedagainstthecontinuedproliferationofmanualizedtreatmentsdevelopedthroughefficacytrialsandbasedonDSMcategoricaldiagnoses,whichareoftenunderutilizedandslowtobeadoptedinclinicalsettings.Withinthetradi-tionalbiomedicalmodeloftreatmentdevelopment,itisestimatedtotake20yearsforatreatmenttobeconsideredefficaciousandeffectiveenoughforbroaddissemination.9 Furthermore, few of the EBTs that makeitthroughthisrigorousvalidationprocessareultimatelytaughtingraduateprogramsoravailabletochildren and adolescents in public mental health set-tings.10Thisdisparitybetweenavailabilityandutiliza-tionofEBTsisrelatedtothenumerousdifferencesbetweenefficacytrialsandactualclinicalpractice.Comparedtoefficacyclinicaltrials,real-worldpracticesettingsaremorelikelytotreatchildrenandfamilieswithmultipleproblems,moreheterogeneousclinicalanddemographicpresentations,moreseverepsycho-

45


pathology,andgreaterfunctionalimpairment.11 Com-paredtoefficacyclinicaltrials,cliniciansinreal-worldpracticesettingsalsocarryhigherclinicalcaseloads.11 Thesedifferencesmayalsohelptoexplainthefind-ing that, when tested against usual care, EBTs have demonstratedeffectsizesthataresmalltomoderateat best.8 ConcernsregardingtheeffectivenessofDSM-basedtreatmentalsoextendstoDSM-basedresearch.Forexample,theNationalInstituteofMentalHealth’s(NIMH)recentlyreleasedResearchDomainCriteria(RDoC),whichisdesignedtoaddressthisinstitute’sassessment that the advances in basic and transla-tionalresearchbasedonaDSMcategoricalapproachhas stalled, and that a focus on underlying mecha-nismsmaybeamoreeffectiveapproachtorealad-vances in behavioral health research.12Brieflydefined,RDoCisadimensionalresearchclassificationsystemthat is rooted in behavioral neuroscience. Within the RDoC framework, diagnoses are based not only on clinicalobservationandpatients’phenomenologi-calsymptomreports,butalsoonadditionalunitsofanalysis(eg,imaging,genes,physiologicalactivity,behavior)inordertobetterreflectthebrain-behaviorunderpinnings of mental health.12 Much research is neededtodefinetheseunitsofanalysissothattheycanbetterinformadiagnosticclassificationsystemthatmorecomprehensivelydescribespatients’clini-calpresentationsandneeds.Theemergingchallengefor clinicians is that the research base, which will result from RDoC, will no longer connect explicitly totheDSM.Assuch,itwillbenecessarytoidentifyways in which RDoC mechanisms can be measured andaddressedinclinicalpractice.Continueddialoguebetween RDoC researchers and the developers of mentalhealthinterventionsshouldresultinEBTsthatmorecomprehensivelyaddressthecomplexitiesofpatients’behavioralhealthneeds.

Transdiagnostic Mechanisms With RDoC, the NIMH urges researchers away from studiesthatrelyoncurrentclassificationsystems(DSM-5,ICD-10)andtowardsthestudyofmecha-nisms, especially those that are common across multipledisorders.Thesemechanismsmayincludebiologicalprocesses(eg,sleep-wakecycles),aswellascognitiveandbehavioralprocesses(eg,attention,perception,socialcommunication).12 In line with

theRDoCinitiative,thetransdiagnosticapproachtobehavioralhealthisthoughttoreduceemotional/behavioral concerns by intervening at the level of themechanism(eg,emotionregulation,sleepdistur-bance),ratherthanatthelevelofthesymptom(eg,tantrums,irritability).Mechanismscanbeconsideredtransdiagnosticwhentheyinfluencetheetiologyand/ormaintenanceofmultipleproblembehaviors.Asde-finedbyEhrenreich-MayandChu,1 these mechanisms mayexistontheintrapersonallevel(eg,cognitions,behaviors,physiologicalprocesses),theinterpersonallevel(eg,parent-childrelations),andonthecom-munitylevel(eg,culturalinfluences,neighborhoodresources).Similarly,Nolen-HoeksemaandWatkins13 describemechanismsaseithermoredistal(environ-mental,distantintimefrompresentingpathology)ormoreproximal(within-person,moredirectlyinvolvedinpathology).Manydistinctprocesseshavebeenidentifiedasmechanisms that underlie and maintain childhood psychopathology, making them appropriate targets forintervention.Theseincludeattentionaldysfunc-tion,14 sleep,15andemotiondysregulation.16Addition-al intrapersonal processes worth considering include distresstolerance,rumination,attributionerrors,self-efficacy,andexperientialavoidance.Interpersonalmechanismsincludeparentingbehaviors,peervic-timization,maritalconflict,abuse,friendships,familyrituals, and parental psychopathology.1 More distal, community-levelmechanismsincludepoverty,ex-posuretoviolence,andprotectiveculturalfactors.17 Consistent with Frieden’s Health Impact Pyramid,18 HudziakandBartelsarguefortheconsiderationofdis-talfactorsandfactorsthathavenottraditionallybeenthe target of mental health assessment and interven-tion,suchasreligiosity,sportsparticipation,stressfullifeevents,andfamilyconflict.AttheirVermontCen-terforChildren,Youth,andFamilies(VCCYF),Hudziakand colleagues aim to develop treatment plans that includenotonlytraditionaltherapybutalso“prescrip-tions”forwellness-relatedprotectiveandpreventiveactivitiessuchasviolinlessons,fitnessregimens,andscreen-timereduction.19 Itquicklybecomesapparentthatinnumerablepro-cessescouldbedescribedastransdiagnosticmecha-nisms.Ehrenreich-MayandChucautionagainstover-inclusiveness,emphasizingabalancebetweenexplanatory power and parsimony.1 The advent of

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RDoCshouldprovidefurtherclarificationabouthowto strike this balance. In the interim, mechanisms that have been shown to impact a range of pediatric clinicalpresentationsandthatrespondtoclinicalin-terventionsshouldbeconsideredforinclusioninthedevelopmentoftransdiagnosticclinicalinterventions.A review of the literature suggests that these criteria aremetbythefollowingmechanisms:(1)parentingpractices,(2)sleepregulation,(3)emotionregulation,(4)informationprocessingdeficits,and(5)experien-tialavoidance.Eachselectedmechanismisdescribedin detail below.

ParentingParentingbehaviorshavebeenimplicatedinthede-velopment and maintenance of a variety of pediatric behavioralhealthdifficulties.20,21Morespecifically,interactionsbetweenachild’sbiologicaltempera-mentandparentingpracticesthatmightbetooharsh,permissive, and/or inconsistent increases the risk fordevelopingunhealthyparent-childinteractions.Theseunhealthyinteractions,inturn,placethechildat increased risk for developing clinically concerning emotionalandbehavioralproblems.Parentalcontrolhasbeenimplicatedasanoteworthytransdiagnosticparentingbehaviorforbothinternalizingandexter-nalizing disorders.22Parentalcontrolisoftentimessubdivided into behavioral and psychological control. Behavioral control is typically viewed favorably and involvesaparentsettingappropriatelimits,imple-mentingeffectivedisciplinetechniques,andpro-vidingadequatesupervision.Psychologicalcontrolfrequentlyhasnegativeconnotationsandinvolvesparentingpracticesthatareoverlycontrolling,suchasconstraining verbal expression or discouraging inde-pendent problem solving, thereby reducing a child’s ability to develop a sense of autonomy and indepen-dence.23 Appropriate behavioral control is typically viewedasaprotectivefactoragainstpediatricbehav-ioral health concerns, whereas high levels of psycho-logicalcontrolhavebeenshowntonegativelyimpactthe development and maintenance of both internal-izing and externalizing disorders.24

Parentsalsoinfluencetheirchild’semotionalandbehavioraldifficultiesbymodelingineffectivebehav-iorsandcopingstrategies(egexperientialavoidance,emotionaldysregulation,informationprocessingbi-ases),whicharethenimitatedbytheirchild.25 Parents

mayperpetuatetheirchild’semotionalandbehav-ioraldifficultiesbyprovidingreinforcementforthesebehaviors. For example, research has shown that a child’sinformationprocessingbiasesarereinforcedthrough discussions with parents, wherein anxious childrenaresupportedinselectingavoidantsolutionsand aggressive children are encouraged to use aggres-sivesolutions.26

Sleep Regulation Amongadults,sleepdysregulationisknowntobeco-morbid with a broad range of psychiatric disorders.27 Though less studied in children and adolescents, sleep disturbance is common among this younger popula-tion.28Furthermore,childhoodsleepdysregulationisassociated with a range of psychopathology, including disruptivebehavior,29 anxiety,30 and depressive symp-toms.31 Harvey et al argue that sleep disturbance is not only descriptively transdiagnostic(ie,commonlyco-occurringacrossvariouspsychiatricdisorders)butalso mechanistically transdiagnostic. That is, Harvey and colleagues posit that sleep disturbance and psy-chopathologyareetiologicallylinked.Theyprovideareview of possible neurobiological pathways that may explainthislink,includingtheassociationbetweencircadian genes and psychopathology, the bidirec-tionalrelationshipbetweensleepdisturbanceandemotiondysregulation,andtherelationshipbetweencircadian systems and dopaminergic/serotonergic functioning.Thegroupoutlinesclinicalimplicationsofthetransdiagnosticnatureofsleepandproposesa modular treatment for sleep disturbance in adults, which could be adapted for use with children and adolescents.15

Emotion Regulation Emotionregulationhasbeendescribedastheman-nerinwhichanindividualmodifieseitherinternalemotionalexperiencesorexternalemotionalstimuli.AccordingtoGross,“emotionregulationreferstotheprocessesbywhichweinfluencewhichemotionswehave, when we have them, and how we experience andexpressthem.”32Morerecentdefinitionshaveincludedincreasinglynuancedconsiderationoftheseparate skills, processes, physiological indicators, and neuralunderpinningsthatcompriseemotionregula-tion.33Despitelackofconsensusregardingitsdefini-tion,emotionregulationisconsistentlyidentifiedas

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apertinentfactorinawiderangeofpediatricbehav-ioral health concerns.34 Theroleofemotionregulationdeficitsinthedevel-opment of both internalizing and externalizing disor-dershasledtoitsconsiderationasatransdiagnosticmechanism.22,34Moreaccurately,emotionregulationcomponents and strategies may be considered as a setoftransdiagnosticmechanisms,includingbothautomaticreactions(temperament,impulsivity,negativeemotionality)andmorevoluntaryoreffort-fulstrategies(eg,executivefunctioningstrategiessuchasattentionalcontrol,inhibition).35 Increasingly, focus has turned to the physiological measurement of emotionalarousal,includingfunctionalimagingstud-iesandmeasurementofcardiacvagalregulation.36,37 Thesestudiesshouldprovideadditionalinformationaboutthetransdiagnosticroleofemotionregulation.

Information Processing BiasesInformationprocessingisdescribedasthecognitiveprocessesthatinfluenceanindividual’sbehavioralresponsetoagivenstimulus.38Biasesininformationprocessing(eg,attention,appraisal,negativethinking)contributetoavarietyofclinicalpresentations,in-cludingmooddisorders,anxiety,disruptivebehavior,andposttraumaticdistress.39Thedistinctionbetweenemotionregulationandinformationprocessingisnotwelldelineated,andseveralprocesses(eg,rumina-tion,attentionbiases)aredescribedunderbothum-brella literatures. For the purpose of this paper, infor-mationprocessingincludesthesequenceofcognitiveprocesses that impact an individual’s response to the environment,withaparticularfocusonrumination,appraisal,andattentionbias.Rumination,appraisal,andattentionbiashaveallbeenidentifiedascognitiveprocessesthatunderliethe development of both internalizing and externaliz-ing psychopathology among children and adolescents. Rumination isdefinedasthepassiveandrepetitiveanalysisofnegativesymptomswiththeabsenceofactiveproblemsolving.Ithasbeendescribedasamechanisticlinkbetweendepressionandanxietyandasatransdiagnosticfactoracrossnumerousdisordersincludingemotionaldisorders,substanceabuse,andeatingdisorders.40Furthermore,ruminationhasbeenfoundtoplayaroleinthetransitionbetweeninter-nalizing problems and aggressive behavior among young adolescent males,34suggestingitsvalueasa

transdiagnosticmechanismthatspansseeminglydistinctareasofpsychopathology.Similarly,biasesof appraisal,orinterpretation,playaroleinmultipleinternalizing and externalizing behavioral health dis-orders.22Thesebiasesintheinterpretationofexter-nalinformationincludemisinterpretationofsocialcuesandcognitiveerrorssuchascatastrophizingandpersonalizing.41Appraisalbiaseshavebeenidentifiedamongchildrendemonstratingsymptomsofdepres-sion, anxiety, and aggression.42 Finally, the presence ofattentionalbiasacrossbothexternalizingandinternalizing disorders suggests its role as a transdi-agnosticmechanism.14 Fraire and Ollendick reviewed theliteratureonattentionalbiasesinchildrenwithcomorbidanxietyandoppositionaldisordersandidentifiedbiasestowardsthreateninginformation(eg,angryfaces),aswellasnegativeinformationingen-eral(eg,preferentialrecallofnegativewords).22 Racer and Dishion presented preliminary evidence regarding therelationshipbetweenbasicattentionprocesses(alertingandorienting)andbothinternalizingandexternalizing symptoms.14 They highlighted the need forbettermeasurementofattentionprocessesandproposedattentiontrainingasapotentiallyeffectivetransdiagnostictreatment.

Experiential Avoidance Avoidance has been described as an occurrence in which “an individual does not enter, or prematurely leaves,afear-evokingordistressingsituation.”43 Chu andcolleaguesprovideadetailedexplanationoftheroleofavoidanceasatransdiagnosticfactoracrossdepression,anxiety,andconductproblems(eg,op-positionaldefiantdisorder,conductdisorder,andattention-deficit/hyperactivitydisorder).Theauthorsexplain that the terminology used to describe avoid-ancediffersacrossdisorders,withavoidanceactingastheunderlyingfunctionofotherprocesses,includingescapefromtaskdemands,rumination,socialwith-drawal,andcallous-unemotionalresponding.Theyproposetheneedforcontinuedinvestigationinordertounderstandthetransdiagnosticrolethatavoidanceplays across disparate disorders. Avoidance as an independent process has perhaps been most thoroughly explored by the developers ofAcceptanceandCommitmentTherapy(ACT)andotherthird-wavecognitiveandbehavioralinterven-tions(eg,DialecticalBehaviorTherapy,mindfulness-

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basedapproaches).44 Experiential avoidance is de-finedasthetendencytoescapeoravoidunpleasantpsychologicalprocessessuchasthoughts,emotions,orsensationsbyattemptingtochangetheformandfrequencyoftheseexperiences.45 The process is a centralcomponentofHayesandcolleagues’Function-al Dimensional approach to diagnosis and treatment, whichparallelsthetransdiagnosticmovementinitsemphasisonfunctioningratherthansyndromal/diag-nosticcategorization.Researchhasdemonstratedthatexperientialavoidanceplaysaroleinadultdepres-sion,anxiety,substanceabuse,posttraumaticstressdisorder,andself-harm.46

Experientialavoidancehasnotbeenaswidelystudiedamong youth. However, there is evidence for the ef-fectivenessofACT,whichtargetsexperientialavoid-ance,intreatingchildandadolescentpsychopatholo-gy.ACThasdemonstratedsuccessintreatingchildrenandadolescentswitheatingdisorders,anxietydisor-ders, and chronic pain, as well as in improving paren-talcopingandparentingpractices.47 Furthermore, experientialavoidanceiswidelyunderstoodtounder-lie various childhood internalizing and externalizing disordersandthuswarrantsattentionasatransdiag-nosticmechanisminpediatricbehavioralhealth.48

Transdiagnostic Intervention Programs Rapidgrowthhasoccurredinthenumberoftheoreti-calandempiricalpapersdescribingtransdiagnosticapproaches to behavioral health. A Google Scholar searchfortheterms“transdiagnosticinterventionpsychology”duringallyearsbefore2010produced670results;asearchforthesametermsinarticlespublishedbetween2010andmid-2015produced4,200 results. Despite this rapid growth in the use of the term transdiagnostic, variability exists with regard tohowthistermisapplied.Amajorityofpublicationsonthetopicoftransdiagnosticinterventionusethetermtodescribeinterventionsdesignedtotreat2highlycomorbidinternalizingdisorders(eg,depres-sionandanxiety),49ormultiplesimilardisorderssuchas anxiety disorders50oreatingdisorders.51 The most promisingexistenttransdiagnostictreatmentsfocusonlyoncomorbidanxietyanddepression,resultinginafailuretoaddressthehighcomorbiditiesbetweeninternalizing and externalizing disorders.

The Unified Protocols As with many areas of psychotherapy research, early modelsoftransdiagnosticinterventionoriginatedin the adult therapy literature.49 The most studied andcitedprogramisBarlowandcolleagues’UnifiedProtocolforthetreatmentofEmotionalDisorders(UP),whichtreatsadultanxietyandmooddisordersconcurrentlyusingtraditionalcognitivebehavioraltherapy(CBT)principles(eg,preventionofavoidance,behavioralexposure,cognitiverestructuring),whilealsoemphasizingemotionalprocesses(eg,emotionawareness,regulation,emotionalavoidance).52 The UPhasdemonstratedefficacyinreducingsymptomsof depression and anxiety in adults with a principal anxiety disorder.53Severalchildandadolescent-focusedinterventionshavefollowedBarlowandcolleagues’leadintreatingcomorbidanxietyanddepression.TheseincludetheUnifiedProtocolsfortheTreatmentofEmotionalDisordersinChildren&Adolescents(UP-C,UP-A),54 which are downward extensionsofBarlow’sUP.TheUP-AwasmodifiedfromtheadultUPtotreatanxietyandmooddisordersinadolescentsages12-17years.LiketheadultUP,theUP-Atargetsemo-tionregulationasacorefeatureofbehavioralhealthandutilizesCBT-basedtreatmentskills(eg,emotionawareness,cognitivereappraisal,preventingavoid-ance,andemotionexposures).TheoriginaladultUPwasmodifiedtobemoredevelopmentallyappropri-ate by reducing the amount of jargon, increasing timeforrapportandmotivationbuilding,increasingfrequencyofexperientialexercises,andadaptingtheprogram to include parents.54 The program has dem-onstratedefficacyintheconcurrentreductionofbothanxiety and depressive symptoms in a sample of 59 adolescentspresentingwithhighratesofcomorbidityand a principal diagnosis of either anxiety or depres-sion.55 AfurtherdownwardextensionoftheUP-A,theUni-fiedProtocolforChildren:EmotionDetectives(UP-C:ED),wasdevelopedtotreatanxietyand/ordepres-sivesymptomsinchildrenages7-12.56TheUP-C:EDisagroup-basedtreatmentthatutilizesdevelopmen-tally-appropriatemodifications(eg,reinforcementthroughrewards,increasedparentalinvolvement)toteach the core concepts and skills that are shared by theotherversionsoftheUP(eg,emotionawareness,cognitivereappraisal,emotionexposures).54 Prelimi-

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naryopentrialresearchsuggeststhattheUP-C:EDmaypreventchild-reportedanxietysymptomsinnon-clinicalpopulations57 and reduce anxiety and depres-sion symptoms in children with a principal anxiety disorder.58 TheUnifiedProtocolsrepresentprogressinamove-menttowardseffectivebehavioralhealthinterven-tionsthatdonotfocusondistinctdiagnosticcatego-ries. In order to meet the varied needs of children who present to behavioral health clinics, however, thescopeoftransdiagnosticinterventionswillneedtoincludeabroaderrangeofclinicalpresentations.Todate,themajorityoftransdiagnosticinterventionprograms focus exclusively on comorbid depression and anxiety. Given that childhood behavior problems represent the most common reason for referral to pediatric mental health services,59 a comprehensive transdiagnosticapproachtopediatricbehavioralhealth will need to be applicable across a broad range ofpresentingconcernsincludingbothinternalizingandexternalizingpresentations.Inclusionofseem-inglydisparateclinicalpresentationswithinthesameinterventionprogramisjustifiedbytheexistenceofsharedmechanisms(eg,avoidance,sleepdisturbance,emotionalregulation),whichweredescribedearlier.Suchbroadapplicabilitywillrequirethedevelopmentofadditionalassessmentandtreatmentapproachesthat focus on underlying mechanisms of psychopa-thology, rather than on symptoms and diagnoses.

The MATCH-ADTC The Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH-ADTC)isdistinctfrominterventionssuchastheUnifiedProtocolinthatitextendsfocuswithcomponents designed to support the treatment of a broaderrangeofproblems,addingdisruptivebehav-iorsandtraumaticstresstotheUnifiedProtocol’sfocus on anxiety and depression.60 The treatment con-sistsof33freestandingmodulesdrawnfromcognitivebehavioral therapy and behavioral parent training, to be used in the treatment of youth ages 7 to 15 years. The modules are selected and applied in an individu-alizedcombinationandsequence,dependingonthepresentingconcernsandtreatmentprogressofapar-ticularchildoradolescent.Treatmentmodules,whichincludetitlessuchasProblemSolving,ActiveIgnor-ing,FearLadder,andLearningtoRelax,areselected

accordingtodecisionflowcharts.Inarandomizedtrialof 174 youths with clinically elevated anxiety, depres-sion,and/ordisruptiveconductsymptoms,MATCH-ADTC was compared to standard manualized treat-ment(cognitivebehaviortherapyorbehavioralparenttraining)andusualcare.Theprogramoutperformedboth control groups in symptom improvement trajec-tories over the course of treatment. Further, youths in theMATCH-ADTCgroupshadsignificantlyfewerdiag-nosespost-treatment(meanof1.23diagnoses)thandidyouthswhoreceivedusualcare(meanof1.86diagnoses),withnosignificantdifferenceinnumberof diagnoses at treatment outset.61 TheMATCH-ADTCisinmanywaysconsistentwithavisionofcomprehensivetransdiagnosticpediatricbe-havioralhealthtreatment.Itisflexible,modularized,and designed to address both internalizing and ex-ternalizingconcerns.However,althoughtheMATCH-ADTCistransdiagnosticinthesensethatitisdesignedtotreatchildrenwithvarieddiagnosticpresentations,treatment planning within the model remains depen-dentonsymptom-focuseddiagnosticcategories(ie,Depression,TraumaticStress,Anxiety,ConductProb-lems).Furthermore,initialevaluationoftheprogramhasfocusedonreductionofsymptomsanddiagnoses,withoutexaminingtransdiagnosticmechanisms.62

AlthoughtheMATCH-ADTCrepresentssignificantprogress in the area of modular treatment approach-es, it was not developed or marketed as a transdiag-nosticinterventionprogram,anditdoesnotincludetheexplicitfocusontransdiagnosticmechanismsthatwouldcharacterizeacomprehensivetransdiagnosticapproachtoassessmentandintervention.Thatbeingsaid,theMATCH-ADTCrepresentsanim-portantmovementtowardsutilizationofthecommonelements across EBTs and development of modular treatmentsthatcanflexiblytargetindividualizedneeds.Ratherthancontinuingtodevelopandvalidatenew,stand-alone,manualizedtreatments,thisnewapproachdrawsuponexistentinterventionresearch.AsChorpitaandcolleaguesnote,“continuedprolif-erationofknowledgeabouttreatmentwillnothelpunlesswegetmuch,muchbetteratsummarizing,synthesizing,integrating,anddeliveringwhatweal-readyhave.”63Usingadistillationandmappingmodel(DMM),ChorpitaandDaleidendefined41treatmentcomponents(eg,communicationskills,exposure,relaxation,behavioralcontracting,timeout)thatare

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common across varied EBTs.64 To bridge the gap be-tween“commonelements”approaches(eg,MATCH-ADTC)andtransdiagnosticapproaches,additionalresearch is needed to clarify whether common ele-mentstreatmentcomponentstargetandeffectivelytreatspecifictransdiagnosticmechanisms.Forexam-ple, it seems likely that the common treatment ele-ment relaxation positivelyimpactsthetransdiagnosticmechanism emotion regulation, which likely leads to a reductioninsymptoms.Researchisneeded,however,toidentifyanddefinesuchrelationshipsamongcom-mon treatment elements, underlying mechanisms, and behavioral health.

Transdiagnostic AssessmentA central impediment to the further advancement oftransdiagnosticresearchandinterventionisthecategoricalandsymptom-focusednatureofexistentassessmenttoolsandmethodology.Giventherelativedearthofmechanism-focusedmeasurementtools,purportedlytransdiagnosticinterventionstypicallycontinuetobasetreatmentplanningontheassess-mentofsymptomsanddiagnosticlabels(eg,anxiety),rather than on an assessment of underlying mecha-nisms(eg,sleepdisturbance,parentingpractices).Itisexpectedthatthistrendwillcontinue,inlargepartduetopayors’requirementsrelatedtotheuseofdiagnosticcategories,aswellasprofessionalattach-menttotheseterms.Transdiagnostictheoristsaimtoshiftfocusawayfromsymptomsanddiagnosticlabelsandtowardsthedrivingmechanisticfactorsthatmoreaccurately explain pediatric behavioral health prob-lems.Althoughmanyskilledcliniciansalreadyattendto the role of mechanisms in their clinical formula-tions,thelackofvalidatedmechanisticassessmenttools limits the extent to which clinicians and re-searcherscanexplicitlyandobjectivelymeasurethesemechanisticprocesses.Becausemechanismsarenotregularly measured, the causal link between mecha-nismsandclinicalpresentationremains,toacertaindegree,theoretical.Muchresearchisneededinordertoboth(1)developreliable,validtoolswithwhichtomeasuremechanisticprocesses,and(2)moreclearlyestablishtherelationshipsbetweenunderlyingmech-anismsandclinicalpresentations.Severalmeasureshavedemonstratedutilityinassess-ingthespecifictransdiagnosticmechanismsdescribedearlier(eg,parenting,sleepregulation,emotionregu-

lation,informationprocessingbiases,andavoidance).Theseinclude,amongothers,theAlabamaParentingQuestionnaire,65 the Parental Acceptance and Ac-tionQuestionnaire,66thePediatricSleepQuestion-naire,67theDifficultiesinEmotionRegulationScale,68 theChildren’sAutomaticThoughtScale(CATS),69 the ResponsetoStressQuestionnaire,70 the Avoidance andFusionQuestionnaire,71theEmotionRegulationQuestionnaire,72andTheParentingScale.73

Although the majority of these measures were not ex-plicitly developed for the purpose of measuring mech-anisms,theirpotentialastransdiagnosticmeasureswarrantsfurtherattentionandstudy.However,giventhat these measures typically assess the presence of individual mechanisms, clinicians must use several measures in order to evaluate numerous mechanisms, whichcanbecomecostlyandtimeprohibitive.Thus,developmentandvalidationofaunifiedassessmentinstrument aimed at simultaneously measuring the presenceofmultiplecoremechanismsisneeded.

PMHI Transdiagnostic Pilot Projects ThetransdiagnosticworkgroupofthePediatricMen-talHealthInstitute(PMHI)atChildren’sHospitalColorado/UniversityofColoradoSchoolofMedicinewasoriginallytaskedwithdesigningatransdiagnosticassessmentandinterventionprogramtoaddressthecomplexneedsofpatientspresentingtothePMHI’sbehavioral health programs. The workgroup began bydelineatingacomprehensive,collaborative,trans-diagnosticassessmentandinterventionprogram.AsshowninFigure1,apatientinsuchaprogramwouldbegin with a comprehensive assessment aimed at identifyingthepresentingconcern,aswellasrelevantunderlying mechanisms.However,duringtheinitialstagesoftheprogramde-velopment process, it became apparent that the lack of validated tools with which to measure mechanisms representedasignificantbarriertotheadvancementofsuchatransdiagnosticprogram.Withoutabetterunderstandingandidentificationofcommon mechanisms that underlie clinical presenta-tions,newly-developedtransdiagnosticinterventionapproachesmaynotbeclearlydistinguishablefromorimproveuponpreviously-developedandpoorly-disseminatedEBTs.Inresponsetothislimitation,thePMHItransdiagnosticworkgrouphasundertakena

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Figure 1.Overviewofaproposedtransdiagnosticassessmentandinterventionprogram,withhypotheticalpatientexperi-ence

series of pilot projects aimed at addressing the mea-surementgapinthetransdiagnosticliterature.Theseprojectshavedifferentiatedthemselvesfromexistenttransdiagnosticresearchbyprioritizingthemea-surement of mechanisms over the measurement of symptomsordiagnoses.Specifically,thePMHItrans-diagnosticworkgroupprojectshavefocusedonthedevelopmentandimplementationofatransdiagnos-ticsemi-structuredclinicalinterviewandthecreationofwrittenparentandchildunifiedmeasuresofcoretransdiagnosticmechanisms.BothprojectsdiscussedbelowreceivedapprovalfromtheOrganizationalRe-searchRiskandQualityImprovementReviewPanelatChildren’s Hospital Colorado. Transdiagnostic InterviewFirst,thetransdiagnosticworkgrouphasbeguntoevaluatethefeasibilityandutilityofanewtransdiag-nosticsemi-structuredinterview,whichiscurrentlyinitsseconditeration.Thisinterviewretainstraditionalintakequestionsdesignedtoidentifysymptomsandevaluate the presence of any psychiatric diagnoses, whilealsoevaluatingthepresenceofpertinentun-derlying mechanisms. At the beginning of the intake appointment,patientsandcaregiversareaskedtoidentifythe3problemsofgreatestconcerntothemand to rate the severity of those problems on a scale rangingfrom0(notatall)to10(verymuch).Thisconsumer-guided“topproblems”assessmentap-proach was developed by Weisz and colleagues74 in an efforttosupportcliniciansinefficientlyandsystem-aticallyusingevidence-informedtreatmentplanning

and progress monitoring tools. Furthermore, the top problems approach has been proposed as a method thatcansupportthestudyofempirically-derivedcon-structs,suchastransdiagnosticmechanisms,whilealsoprovidingfamily-centeredcareandmaintainingpsychometricintegrity.Followingtheidentificationoftop problems, PMHI pilot clinicians support families inevaluatingthepresenceandimpactofdifferentmechanismsonthetop3identifiedproblems.Duringthefirstiterationoftheinterview,mecha-nisms were assessed through a series of targeted questions,whichwerelargelyinformedbybehavioraltheoryandtheliteratureonfunctionalassessment.Anoperationaldefinitionofhowthesemechanismstranslatedintobehaviors,informationregardingtheantecedentsandconsequencesassociatedwithdiffer-ent mechanisms, and strategies employed to manage these mechanisms were obtained. See Table 1 for an exampleofpertinentquestionsincludedinthisfirstiterationofthePMHI’stransdiagnosticclinicalinter-view.Approximately22transdiagnosticinterviewswerecompletedintheinitialphaseofthisproject.Cliniciansreportedmoderatesatisfaction(1=Stronglydisagreeto6=Stronglyagree;M=3.88)withthenewtransdiagnosticintakeprocessandidentifiedthefol-lowingmechanismsasmostbeneficialforassessmentanddiagnosis:emotionregulation(M=4.87),parent-ing(M=4.81),andexperientialavoidance(M=4.64).Clinicians’qualitativeresponsesindicatedthetrans-diagnosticintakeprocessyieldedcriticalinformationforcaseconceptualization,differentialdiagnosis,and treatment planning. However, responses also

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revealed concerns regarding the length of the transdi-agnosticinterview,whichlastedupto120minutesinduration.Baseduponclinicianfeedback,modificationsarecurrently underway to address concerns regarding thefeasibilityofthetransdiagnosticinterviewandtocontinuetoenhanceitsutilityinidentifyingmecha-nisms and informing treatment planning. The transdi-agnosticworkgroupisbuildinguponthePMHIout-patientclinic’scurrentintakeprocess,expandingtheoriginal90-minuteintakeinterviewto2,60-minutesessions.Duringthefirstvisit,familieswillparticipateinatraditionaldiagnosticinterviewandcompleteawrittenmeasureoftransdiagnosticmechanisms,whichisdescribedinthenextsection.Attheendofthisfirstvisit,theclinicianwillsupportfamiliesinidentifyingatargettopproblem,aspreviousyde-scribed.For1week,familieswilluseahome-basedworksheetaimedattrackingthesituations,thoughts,feelings, behaviors, and outcomes associated with this top problem. During the second visit, families will engageinarevisedsemi-structuredclinicalinterviewinformedbyfunctionalassessmentandbehavior-chain analysis principles in order to gather informa-tionregardingunderlyingmechanismsandfunctionalimpairments. At the conclusion of the second visit, cliniciansandfamilieswilldiscussevaluationfindings,engageinpsychoeducationregardingthetransdiag-nosticapproachtotreatment,andcollaborativelydevelop a treatment plan that addresses mechanisms andemphasizesboththereductionofimpairmentandthepromotionofwellness.

Transdiagnostic MeasuresInarelatedpilotproject,thePMHItransdiagnosticworkgroup is currently working to develop and vali-date2transdiagnosticmeasures,a62-itemParentTransdiagnosticMechanismQuestionnaire(PTMQ)anda39-itemChildTransdiagnosticMechanismQuestionnaire(CTMQ).Thesemeasuresaimtoevalu-atethepresenceofmultiplecoremechanismssimul-taneously,asnocurrently-validatedmeasuresareavailable to accomplish this goal. Item development was guided by relevant theories underlying a transdi-agnosticapproachtopediatricmentalhealth.Specificitems were generated based on a review of the em-piricalliteratureofpertinentmechanisms,asoutlinedabove.Itemswithhighfactorloadingsonpreviously-

validated measures were referenced to inform the developmentofspecificitemsoneachmeasure.SeeTable 2 for a summary of items referenced from other measures, as well as their associated factor loadings baseduponpreviously-conductedstudiesexaminingthepsychometricpropertiesoftheseitems.Thesemeasures have been incorporated into the PMHI transdiagnosticassessmentprocess(describedintheprevioussection),astheyprovidehelpfulsupplemen-talinformationaboutunderlyingmechanismsandfunctionalimpairment.Currently,themeasuresarebeingcompletedduringthefirstsessionofthe2-stepintakeprocessbyallcaregiversandbyallpatientsages8andolder.Thesenewly-developedtransdi-agnosticmeasureshavebeencompletedbyasmallsubsetofpatientsandcaregiversbothtoevaluatethereadability of the items developed and to assess the feasibilityofcompletingthesemeasuresduringanin-take appointment. Preliminary data have demonstrat-ed good understanding of the items on both the child andparentmeasures,andcompletingthesemeasuresduring the intake appointment has been shown to be feasible. Future studies aimed at examining the psy-chometriccharacteristicsofthismeasurewithalargersample,identifyingclinicalcut-offscores,clarifyingtherelationshipbetweenthepresenceofunderly-ingmechanismsandemotional-behavioralproblems,andevaluatingtheproposed5-factormodelfortheseinstrumentsusingconfirmatoryfactoranalysiswillbeneeded.

ConclusionAstranslationalmentalhealthresearchturnsitsat-tentionfromsymptomsanddiagnosestotransdiag-nosticmechanisms,clinicalprogramshavetheoppor-tunitytodevelopandusenewtoolsandfindingstoreshapeclinicalinterventionsandbetteraddressthecomplexbehavioralhealthneedsofpediatricpatients.InkeepingwiththeaimsofRDoC,closerexaminationoftransdiagnosticmechanismssuchasthosede-scribedinthispaper(eg,parenting,sleepregulation,emotionregulation,informationprocessingbiases,andexperientialavoidance)willprovidevitalinforma-tionabouttheetiologyandmaintenanceofchildandadolescent behavioral health problems. More work isneededtoexpandpediatrictransdiagnostictreat-ments to include externalizing as well as internalizing symptoms,topushbeyondtraditionalmodelsofin-

53


terventiondevelopmentanddissemination(ie,manu-alization),andtodevelopeffectiveassessmenttoolsforidentifyingpertinenttransdiagnosticmechanisms.Withcontinuedresearchandpracticalapplication,the

burgeoningtransdiagnosticmovementhasthepoten-tialtotransformthewayinwhichbehavioralhealthdisorders are conceptualized and treated.

Table 1. Excerptfromoriginaltransdiagnosticinterview,includingtopproblemsandmechanism-focused questions.

PROBLEM LIST(0=Notatall;10=Verymuch)Top 3 Problems (per caregiver): Problem 1: Problem 2: Problem 3:

Top 3 Problems (per child/adolescent): Problem 1: Problem 2: Problem 3:

MECHANISM (eg,experientialavoidance)Patientavoids/strugglestotoleratewhichofthefollowing:bodilysensations,memories,thoughts,emotions,situ-ations,etc.

Examples of avoidance: Frequency:___timesper{day,week,month,year}for___{lengthoftime}.

Avoidance most likely:

When: Where: With: While:

Avoidance least likely:

When: Where: With: While:

Antecedents/triggers of avoidance: Consequences(punishmentorreinforcement)ofavoidance: Avoidance usually stops when:

Strategies to address avoidance: Strategiesimpactedavoidance?

Avoidanceimpacts{Problem1}by: Avoidanceimpacts{Problem2}by: Avoidanceimpacts{Problem3}by:

54


Table 2.FactorloadingsandratingscalesassociatedwithdevelopmentofitemsforCTMQ/PTMQ

Note:Factorloadingsarebaseduponpreviouslyconductedstudiesexaminingthepsychometricpropertiesoftheseitems.

RatingScale(s) FactorLoading ItemEmotionRegulationDifficultiesinEmotionRegulationScale68 .79 Icannotpayattentiontoanythingelse.DifficultiesinEmotionRegulationScale .85 I can’t control what I say or do.

DifficultiesinEmotionRegulationScale .88 I have trouble understanding how I am feeling.EmotionRegulationQuestionnaire72 .66 I try to hide my feelings or keep my feelings to myself.InformationProcessingResponsetoStressQuestionnaire70 .72 I deal with my problems by wishing they would go away.EmotionRegulationQuestionnaire .76 WhenIwanttofeelbetteraboutsomething,Ichangethe

way I’m thinking about it. Children’sAutomaticThoughtScale69 .80 Ithink,“Iamworthless.”Children’sAutomaticThoughtScale .83 Ithink,“Mostpeopleareagainstme.”ExperientialAvoidanceResponsetoStressQuestionnaire .81 I deal with a problem by pretending it has not really hap-

pened.ResponsetoStressQuestionnaire .79 Iengageinotheractivities(egeat,sleep,playvideogames)

to distract myself from feeling upset.AvoidanceandFusionQuestionnaire71 .59 I push away thoughts and feelings I don’t like.ParentingPracticesAlabamaParentingQuestionnaire65 .68 I provide rewards or give something extra when my child is

behaving well.TheParentingScale73 .74 IfmychildgetsupsetwhenIsay“no,”Ibackdownandgive

into my child.ParentalAcceptanceandActionQues-tionnaire66

.59 I try hard to avoid having my child feel sad, worried, or angry.

SleepRegulationPediatricSleepQuestionnaire67 .89 Howwouldyourateyourchild’ssleepqualityoverall?

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Infant and Preschool Adaptations of Inhibitory Tasks

InfantandPreschoolAdaptationsofInhibitoryAdultTasks Associated with Psychiatric Illness

Background

Psychiatricdiseaseisoftenconceptualizedasaneurodevelopmentalresultofadecades-longin-

terplaybetweengeneticandenvironmentalfactors.Most modern versions of this Neurodevelopmental Hypothesis1,2propose2particularlycriticalperiodsof brain development: a perinatal period where vulnerability is established and a later childhood, adolescent, or early adult period where vulnerability becomes symptomatology. Brain changes that occur duringtheperinatalperiodarenotdeterministicinthat the majority of children at risk will never devel-op a chronic psychiatric disorder. In a similar fashion, geneticandenvironmentalfactorsthatinfluencetheadolescent or young adult emergence of psychiat-ric symptoms are far less strongly associated with increasedriskinnon-vulnerableindividuals.Comprehensivepreventionstrategiesneedtoin-cludeevaluationandinterventionatmuchyoungerages: during pregnancy, infancy, and preschool

years.Tothiseffect,theNationalInstituteofMentalHealth has called for an increase in research focus-ing on the developmental aspects of psychiatric diseaseas1of4mainstrategicobjectives(StrategicObjective#2,NIMH).3 There have been increasing questionssurroundinghowtoapproachthestudyofpsychopathology in general. Many psychiatric symp-toms appear clinically similar across a wide range of diagnoses.Forexample,activepsychosisinsome-one who has a diagnosis of bipolar disorder may be clinicallyindistinguishablefromthatinsomeonewhohasschizophreniaorschizoaffectivedisorder.Additionally,someindividualswiththesamediagno-sismayhavealargevariationinsymptomaticpre-sentation.Supportingthesymptomaticoverlapfre-quentlyseeninclinicalpresentations,researchhasthusfarbeenunabletoassociatecurrentspecificdi-agnoseswithquantifiablebiomarkersorgeneticlo-cales. Again using psychosis as an example, despite a significantefforttoidentifyspecificgeneticmarkers,

Elizabeth Calvin, MD; Amanda Hutchinson, MD; Randal G. Ross, MD*

AbstractManypsychiatricdiseasesareoftenconceptualizedasneurodevelopmental,wheretheonsetofclinicallydi-agnosableillnessistheendresultofayears-long,orevendecades-long,alterationinbraindevelopment.Theaberrantbraindevelopmentcanoriginateasearlyasthepre-orearlypost-natalperiod;thus,effortsaimedatunderstandingandpreventingdiseaseonsetaregoingtorequiremethodologiesappropriateforuseinyoung children and infants. One approach to develop early developmental methodologies is to take methods usedinthestudyofadultsandmodifythemforinfantorpreschooluse.Thisreviewexploresthepotentialforuse,ininfantandpreschoolpopulations,of4commonly-employedtasksofcognitiveinhibitioninadults:theantisaccadetask,prepulseinhibition,P50sensorygating,andsmoothpursuiteyemovements.OnlyP50sen-sorygatinghasreceivedmuchattentionasamarkerofearlyvulnerabilitytolateronsetofpsychiatricillness;however,infantvariantsofthesemethodologiesarealsoavailablefortheantisaccadetaskandsmoothpursuiteyemovements.Byutilizingadaptationsoftraditionaladulttasks,researchfocusedontheearliestphasesofdevelopmentisfeasibleandhasthepotentialtoimproveprimarypreventionofpsychiatricillness.

* Author Affiliations: Division of Child and Adolescent Psychiatry, Departments of Psychiatry, (Drs Calvin, Hutchison, and Ross) and Pediatrics (Dr Ross), University of Colorado School of Medicine, Pediatric Mental Health Institute, Children’s Hospital Colorado. Dr Calvin is currently practicing in Round Rock, Texas. Dr Hutchison is currently in private practice in Denver, Colorado.* Corresponding Author: Randal G. Ross, University of Colorado School of Medicine, Department of Psychiatry, Campus Box F546, 13001 E. 17th Place, Aurora, CO. 80045. USA tel:+1-303-724-6203, fax:+1-303-724-6207, [email protected].

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Calvin, Hutchinson, Ross

currentlyidentifiedgeneticvariantsappeartoconfersimilarriskacrossmultipledisorders.4 Thus, the NIMH has also called for the development of a new way of classifying psychiatric disease based on neurobiologi-calmeasuresandobservablebehavior(Strategy1.4).3 Tothisend,basicdomainsoffunctioningarebeingstudiedacrossmultiplediagnosesandalongmultiplelevels.Thesediagnosticanddevelopmentaldilemmasare present globally in psychiatry; however, to illus-trate,wewillutilizeonefacetoffunctioning,cognitiveinhibition,asamicrocosmofpossibletranslationandfuture research.In adults, there are several tasks that have been developedtostudycognitiveinhibition.Performancedeficitsinthesetaskshaveemergedaspotentialen-dophenotypes,orcharacteristicsofgenesthatpredis-pose an individual to disease.5Theseinclude(butarenotlimitedto)P50sensorygating,inhibitionofpro-saccadesduringanantisaccadetask,smoothpursuiteyemovementaberration,andpre-pulseinhibition.These tasks could prove ideal for studying develop-mental trajectories and early symptomatology. How-ever, in children of certain ages, limited developmen-talcapacityandthedifficultyfacedincommunicatingresearchproceduresmakeutilizationofthesetasksdifficulttoimpossible;simplertasksmustbeused.Inrecentyears,recognitionofthesedifferencesandthedesiretoexaminedevelopmenthasspawnedmultipleinfantandpreschooladaptationsofadultinhibitorytasks. This manuscript reviews infant and preschool versionsofadultmeasuresofcognitiveinhibition,highlights what has been shown through them thus far,andexaminespotentialfutureareasofresearch.We plan to illustrate that tasks have been associated with risk of later disease onset, have developmentally appropriate correlates, and are usable in preschoolers and infants.

MethodWeused“eyemovements,”“saccade,”“sensorygating,”“P50,”“prepulseinhibition,”and“smoothpursuit”asindependentsearchwordstoidentifyfulltextsintheOVIDandPsychInfodatabasesbeforeJuly2014. Each search was limited to studies of “all chil-dren(ages0-18years).“Thereferencelistsofeacharticlewerefurtherexaminedtoincludestudiesnotlisted in above databases. A more limited search was

completed for the same key words for adult popula-tions.

AntisaccadeRapideyemovements,whichdirectgazetoaspecificlocationinvisualspace,aretermed“saccades.”Theantisaccadetaskisanocculomotorparadigmwhereintheparticipantwatchesthepresentationofavisualcue, and then is instructed to move his eyes to the mirror image of that cue while his eye movements arerecorded(Figure1).Cognitiveinhibitionistestedinthatonemustinhibitthemorebiologically-pro-grammed, or prepotent, response of looking at a new visual cue, and instead follow the examiner’s instruc-tionstolookattheemptyvisualspaceatitsmirrorimage.

Adult LiteratureThis task has been used extensively to study disor-deredpsychiatricpopulationsinadults.Despitetypi-cal performance on saccadic movements to a target, schizophreniapatientshaveconsistentlybeenfoundtohaveanincreasederror-rateontheantisaccadetask, moving their eyes to the presented visual cue insteadofinhibitingthatresponseandlookingtowardits mirror image.6-10Patientswithotherpsychoticillnesses, including bipolar disorder and major depres-sivedisorderwithpsychoticfeatures,havealsobeen

Figure 1. Exampleofantisaccadetask.Theparticipantlooksatafixationpoint(upperleft),whichisreplacedbyastimulus(lowerleft).Theparticipantisaskedtoinhibittheprepotentresponseoflookingatthestimulus(upperright),andinsteadlookstothemirrorimageofthatstimu-lus(lowerright).

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foundtoexhibitanincreasederrorrate,particularlyduringinitialpsychoticepisodes,11,12 though some studieshavefailedtoshowincreasedantisaccadeer-ror rates in those with bipolar disorder.13,14 Many stud-ies have also found an increased latency, or decreased speedofresponse,incorrectantisaccadesinschizo-phrenia,8,9,12,13,15furthersuggestingincreaseddifficultyof this task for those with psychosis.TheinitialConsortiumontheGeneticsofSchizophre-niaanalysesfoundantisaccadedeficitstobesignifi-cantlyheritablewithaheritabilityestimateof42%.16 Similarly,unaffectedfirst-degreerelativesofpsychoticprobandswithantisaccadicabnormalitiesalsohavepoorerperformanceontheantisaccadetask.6,17,18 Thus,theantisaccadetaskappearstobeamarkerofrisk at least for schizophrenia.

Child/Adolescent LiteratureInchildrenandadolescents,developmentaldiffer-encesintheantisaccadetaskmustbeconsidered.Theyounger the child, the more slowly and inaccurately the task is performed. Adult performance in latency isnotachieveduntilearlyadolescenceandaccuracycontinuestoimproveintoearlyadulthood.19-22 Despite thesedevelopmentally-limitedcapacities,increasederrorshavestillbeenvisualizedinchildrencurrentlydiagnosedwithADHD,autismspectrumdisorders,reading disorders, obsessive compulsive disorder, anx-iety, depression, psychosis, and bipolar disorder.23-25 Similartotheadultliterature,ithasbeenestimatedthat greater than half of the variance in performance inchildrenisduetogeneticinfluences.26

Preschool/Infant AdaptationsGivingverbalinstructionstoapreschooleroraninfantisproblematictoimpossiblegivenvaryingabili-tiesinreceptivelanguage.Additionally,adultmethod-ologytypicallycallsforheadrestriction(usuallywithabitebarorchinrest),butinfantsandpreschoolersarelesslikelytotolerateheadfixation.Further,infantscontrolthedirectionoftheirgazeusingcoordinatedhead and eye movements,27 so the head must be free toobservetypicallyutilizedgaze.Instudyingantisaccadesininfantsorpreschool-ers,cognitiveinhibitionmuststillbetested.Inotherwords, the infant must have the choice to look at a stimulus,butinhibitthatresponseandlooktothemirrorimageofthatstimulusinstead.Intheinfant

antisaccadeparadigm,28,29 subjects are encouraged tomakeaneyemovementawayfromthecue(anantisaccade)bymakingthesecondstimulusmoreattractivethanthecueitself.Infantsviewafixation,followedbysimultaneouspresentationofthefixa-tionandthecue,andafteradelay,amoreattractive(morevisuallystimulating)targetappearsoppositethelocationofthecue.Adecreaseinsaccadestowardthecueisobservedovertimeasinfantslearnthatthecuepredictstheappearanceofanattractivestimulusatthecontralaterallocation.Headmovementshavebeenexaminedbypositioningasteelballbearingonthe infant’s forehead, enabling recording of head po-sition(alongwitheyeposition)utilizinginfraredlight(Figure2).Withthesemethodologicalchanges,anti-saccade responses occurred on an average of 25.9% oftrials(8.3outof32)ininfantsaged3to11monthsascomparedtosaccadestowardtheinitialcue,whichoccurredin28.6%(9.2outof32)oftrialsininfantswithnoknownperinatalcomplications.Inotherwords, infants responded to 50% of presented trials, and of the trials they responded to, they performed antisaccadesapproximately50%ofthetime.27

Figure 2. ExampleofanInfantAntisaccadeTask.Ontheleft,presentationofafixationimageisfollowedbystimu-lus(orcue)presentation,whichisinturnfollowedbyadelayandthepresentationofamoreattractivestimulusatthemirrorimageoforiginalstimulus.Asinfantslearnthestimulusprecedesthepresentationofamoreattractivestimulus,theywillcompleteanantisaccadetothelocationwheretheyexpectthemoreattractivestimulustoappear.

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Preschoolers/Infants at Risk for Psychiatric IllnessNopaperswerefoundexaminingantisaccadesinpre-schoolers or infants at higher risk of later psychiatric illness.

Summary Theantisaccadetaskisaneffectiveresearchtoolwhere performance, in adults, is heritable and as-sociatedwithpsychoticillness,andanadaptedtaskhas been used successfully in infants. No papers were foundexaminingantisaccadesinpreschoolersorinfants at higher risk of later chronic mental illness givengeneticorenvironmentalriskfactors.Research-ers may be hesitant to perform this task in younger populationsgiventhelikelihoodofextremelyhigherrorratesandpresumedlackofspecificityinas-sociationwithdiagnosisgiventhehighnumberofdiagnoses associated with poor performance in child-hood. However, the infant error rate of 50% is the sameaschildrenaged5-8inthetypicalantisaccadetask.22Inconsideringutilizationofthistask,itmaybe helpful for the subject to undergo more trials to facilitateagreaterresponsepercentage,particularlygiven that learned behavior is necessary to elicit an antisaccadetoananticipatedmoreappealingtargetstimulus.Additionally,somecautionmustbetakenwhen comparing the adult and infant results as the taskshavefundamentallydifferentprotocols,andeyemovementsthemselvesmaybesomewhatdifferentinchildren and adults.23

Smooth Pursuit Eye Movements While performing smooth pursuit eye movement tasks,theparticipantwatchesamonitor,whichpres-ents a moving visual target. The individual is instruct-ed to keep his eyes directly on the target and follow movements as closely as possible while correspond-ing eye movements are recorded. Several necessary componentabilities,suchaspredictionoftargetmovement, maintenance of eye movement velocity, andcognitiveinhibitioncanbestudiedbylookingatspecificportionsofsmoothpursuit.Cognitiveinhibi-torydysfunctioncanbeseenwhensaccadicmove-

mentsintrude,becausetoutilizesmoothpursuit,thesaccadic system must be inhibited. In other words, onecanpassivelyexaminetheparticipant’sability,orlackthereof,toinhibitsaccadeswhileutilizingsmoothpursuit(Figure3).

Adult LiteratureGlobal detriments in smooth pursuit eye movement taskperformancewasfirstobservedinschizophrenicpatientsintheearly1900’s.31 It is now one of the mostreplicateddeficitsinthepsychophysiologicalliterature on schizophrenia.7,32 Smooth pursuit abnor-malitieshavebeenfoundinindividualswithultra-highclinical risk of developing psychosis,33 schizotypic features,34 bipolar symptoms and psychosis,35 bipolar disorder,36,37 acute mania,38andpsychoticsymptomsassociated with PTSD.39 Biologicalrelativesofpatientswithschizophreniahave also been shown to exhibit high rates of dysfunc-tionalsmoothpursuiteyemovements,15,30,40-42 and heritabilityhasbeenestimatedatbetween40%and60%.43 Global measures of smooth pursuit eye move-mentsappeartoberelativelyunaffectedbymostantipsychoticmedication44,45orantidepressants,andtheredoesnotappeartobeasignificantcorrelationbetweenacutepsychopathologyordurationofill-ness.32,45-47Atypicalneuroleptics,suchasclozapineor

Ontheright,exampletracingsareshown.Gaze(blueline)iscalculatedutilizingeye(red)andhead(green)positions.Examplesofinfants(1)3-5months,(2)6-8months,and(3)9-11monthsareshown.Adaptedwithpermission.27

Figure 3. Sample tracing of smooth pursuit tracking from anindividualwithpresumedgeneticriskofschizophre-nia(childofaparentwithschizophrenia).Thefirstarrownotesananticipatorysaccadewherethesubject’seyesjumpaheadofthemovingvisualstimulus.Thesubjectthenutilizessmoothpursuitandmakesacatch-upsaccadewhenhiseyesfallbehindthetargetposition.Adaptedwithpermission.30

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other psychotropics, such as lithium, however, may adverselyaffectsmoothpursuit.48-50

Withtheconsistentfindingthatglobaleyetrackingand smooth pursuit are impaired in schizophrenia patientsandtheirrelatives32,41,51 as well as in other disorderssuchasautism,52 depression,53 Parkinson-ism,54 and ADHD;23,55additionalresearchhassoughttodeterminespecificallywhicheyemovementcom-ponents are most likely endophenotypes. The heri-tability of generic saccades in smooth pursuit has beenestimatedat66%,catch-upsaccades(saccadesoccurringinthedirectionoftargetmotionthatmovetheeyefromapositionbehindthetargettoapositionnearthetarget)at61%,andanticipatorysaccades(intrusivesaccadesoccurringinthedirectionoftargetmotionthatmovetheeyefromapositiononornearthetargettoapositionaheadofthetarget)at62%.43 Ameta-analysisexamining18componentmeasuresofeyemovementdysfunctionfoundthatonlyantici-patorysaccades(andnotgenericsaccadesthatoccurwithinsmoothpursuit)wereincreasedinrelativesofthose with schizophrenia.51

Additionally,severalcomponentsofsmoothpursuiteyemovements,includinganticipatorysaccades,havebeenfoundonlyinschizophrenicpatientsandareabsentinnormalsubjectsorrelativesofdepressedpatients.56Afurthersubsetofanticipatorysaccades,leadinganticipatorysaccades(whicharesmallerinamplitude)arealsobothpresentinunaffectedrela-tivesofschizophrenicprobands57anddifferentiatepatientswithschizophreniafromthosewithADHD,55 furthersupportingpossiblespecificitytoschizophre-nia.Leadingsaccadesalsoappeartobesensitive58 withalargeeffectsize,32specific,55andtiedtogeneticvulnerability.30 However, it should be noted that not allstudieshavefounddifferencesinanticipatorysac-cadefrequency59 or indicated stability in this measure overtime.46

Child/Adolescent Literature Smooth pursuit tracking improves from the ages of7-15,60 and by late adolescence, smooth pursuit reachesadultlevelsoffunctioning,61,62 with age expected to account for 20% of the variance.60 How-ever, some individual components of smooth pursuit mayhavedifferentmaturationalrates.Forexample,leadingsaccades(smallanticipatorysaccades)maybematurebytheageof6,andanincreaseinfrequency

ofleadingsaccadeshasdifferentiatedchildrenatriskof developing schizophrenia.63 Higherratesofsmoothpursuiteye-trackingdysfunc-tion(withsomestudiesincludingabnormalitiesincatch-upandanticipatorysaccades)havebeenseenin children with schizophrenia,64,65 adolescents with a history of schizophrenia onset in childhood,64,66 and inteenagerswithpsychosisnototherwisespecified.64 Theproportionoftotaleyemovementtimespentinanticipatorysaccadeshasalsobeenshowntodiffer-entiatethosewhoaremorelikelytocarrygeneticriskfactors for schizophrenia,30 children of a schizophrenic parent,67 and in children who themselves have schizo-phrenic symptoms.30Anincreaseinanticipatorysac-cades has also been seen in childhood onset schizo-phreniapatientsrelativetobothnormalcontrolsandchildrenwithADHD,indicatingthatthedeficitsseeninschizophreniacannotbeattributedtoattentiondysfunctionalone.66Additionally,increasedfrequen-cies of leading saccades appear to be present in 94% of children with schizophrenia compared to only 19% of typically developing children.63 Poor performance has also been seen in parents and otherfirst-degreerelativesofthosewithchildhoodonset schizophrenia,63,65,68 and in teenage children with a schizophrenic parent.69

Preschool/Infant AdaptationMany studies have found smooth pursuit in early infancy,70-72eveninthefirstfewdaysoflife,73 with smoothpursuitconsistentlyemergingby4-8weeks,andhavingsignificantlyimprovedby4-6monthsofage.71,74,75

Inolderchildrenandadults,thistasktraditionallyrequiresheadimmobilization,suchaswithachinrestandforeheadstrap.However,infantsutilizebothheadandeyemovementstoinitiateandcontinuesmoothpursuit.71 Head tracking also increases with age and hasalargelagtime,withthecontributionoftheheadincreasingovertimeinthefirstseveralmonthsof life.71Differentsubjectsmayalsoutilizedifferentproportionsofheadandeyemovementsinordertoattempttostabilizegaze.76 Here also, eye tracking is simply harder to record given smaller facial dimen-sions.Higher rates of variability are also found,71,77,78 fre-quentlyleadingtorejectionofdatafarfromthe

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mean,andgreaterfluctuationsinattentionmayaffectresults.64,77Resultsmaybeaffectedbyanxietyandfatigue,78whichmaybedifficulttoquantifyorstan-dardize.The ability of an infant to track also depends on the size and speed of the target,71 and younger infants spendlesstimeingeneralutilizingsmoothpursuit,witha1-month-oldtypicallybeingengagedinsmoothpursuitapproximately40%ofthetimeascomparedto 90% in adults.75 Smooth pursuit in infants is also affectedbyhistoryofprenatalcorticosteroids,gesta-tionalage,birthweight,bronchopulmonarydysplasia,retinopathyofprematurity,periventricularleukoma-lacia, and a history of intraventricular hemorrhage,76,79 makingscreeningandparticipantselectionofutmostimportance.Opto-electronicdeviceshavebeendevelopedwithLEDstorecordtheheadpositionoftheinfantandminiatureelectrodestorecordelectro-oculographicdata from the outer canthi,71,76enablingdualquantifi-cationofgazeandsmoothpursuit.However,optimalparameters regarding target size and speed for spe-cificagerangeshaveyettobeelucidated.

Preschoolers/Infants at Risk for Psychiatric IllnessOne report found that infants aged 6 months who were exposed to prenatal maternal anxiety, as compared to those without this risk, exhibited less percentageoftimeinsmoothpursuit,withmorefrequentforwardsaccadicactivity.80 No other papers were found examining smooth pursuit in preschoolers or infants at higher risk of psychiatric illness.

SummarySmooth Pursuit Eye Movement tasks appear ready for useininfantsandpreschoolers.Inadults,dysfunctionis reliably seen in those with psychosis, those at risk ofpsychosis,andintheirbiologicalrelatives.Thisdatahasbeenconfirmedinadolescentsandchildrenwithpsychosis as well. Component measures that may more clearly represent endophenotypes for schizo-phrenia and psychosis have also been found. In infants, global smooth pursuit tracking measures havesignificantlyimprovedonlymonthsafterbirth,and component measures may also mature prior to theentiretrackingsystem,furtherincreasingthepos-sibility that studies in younger children are plausible.

Whenexaminingdifferencesbetweenthosewithpsy-chosis or its risk and controls, some have argued that attentionmaymediatedifference.However,whileattention-enhancingmaneuversimprovesmoothpursuit of typical individuals and those with schizo-phrenia,itdoesnotabolishthedifferencebetweenthem.81,82Additionally,somemaybereluctanttoconductstudieswithoutoptimalparametersregard-ing target size and speed for younger age ranges. If similaragerangeswereutilizedbetweenthe2com-parison groups, however, these concerns could be accounted for.

Prepulse InhibitionPrepulseInhibition(PPI)isanauditorytaskwhereintheparticipantlayssupineinareclinedchairwithhisorhereyesopen.Astartlestimulusofbroadbandnoiseispresentedafteraprepulsestimulusoflowerintensity; movements of the orbicularis oculi muscles arerecorded.Cognitiveinhibitionispassivelytestedinthatthepresenceofaprepulsecausesinhibitionoftheparticipant’sresponsetothestartlestimulusasevidencedbyadiminishedresponse(Figure4).

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Figure 4.ExampleofPrepulseInhibition(PPI).Ontheleft,atypicalresponsetoanauditorystimulusisshown.Ontheright,PrepulseInhibition,asevidencedbyadiminishedresponse,isachievedwiththeadditionofaprepulse.Adapted with permission. 83

Adult LiteratureThis task has been well described in adult popula-tionswithpsychopathology.Forexample,althoughinitialstartlereactivityisthesame84 compared to those without a known psychiatric disease, those withschizophreniacontinuetohavealargerstartleresponse, as measured by greater movement of the orbicularis oculi muscles, despite the presence of a prepulse.85-88ThisdeficientPPIhasbeencor-relatedwiththepositiveandnegativesymptomsofschizophrenia85 and has also been seen in those with schizotypal personality disorder,89 as well as in some studies of those with bipolar disorder.90DeficitsinPPIhave been seen in individuals at risk for and currently experiencingtheirfirstepisodeofpsychosis84,91 and have also been noted in those with acute mania92 as opposed to those with remission of bipolar symptom-atology, where normal levels of PPI have also been described.93

Firstdegreerelativesofthosewithschizophreniaandbipolar disorder have been found to exhibit decreased PPI.90,94,95 Heritability of PPI in those with schizophre-niahasbeenestimatedat32%,16suggestingthatPPIisalsoamarkerofgeneticvulnerabilitytodisease.It should be noted that the details of the task have beenshowntohavesignificanteffectsonresults.Forexample,weakerprepulses(2dBabovetheback-ground),producefacilitation,oralargerstartlere-sponsewiththepresentationofthestimulus,85 and more intense prepulses typically produce a larger PPI effect.85,96 Other subtle changes in the background noise,prepulse,andstimulusmayalsoalterresults.85 Further,patientcharacteristicscontributetomanifes-tationsofPPI.Gender,97-100 smoking status,100,101 cur-rent symptomatology,85 whether or not the individual isaskedtoattendtothestimulus,102-104 and treatment withantipsychotics(whichhavebeenassociatedwithimprovedprepulseinhibitioninsomeinstances)86,88,100mayalsoproducevaryingeffects.

Child/Adolescent LiteratureAdolescentswhohaveearlypsychoticsymptomssuggestiveofhigherriskfordevelopingschizophreniahavealsobeenfoundtoexhibitdeficitsinPPI,and,similar to adults, clinical improvement and treatment withmedicationhasbeenassociatedwithimprovedinhibition.105,106However,deficitswerenotfoundinmedicated,euthymic,non-psychoticchildrenwithbipolar disorder107 or in children at risk of anxiety.108 PPI typically reaches adult levels somewhere between 8 and 9 years of age,109-111 and again similar to adults, attentionfacilitatesprepulseinhibitioninkids.112

Preschool/Infant AdaptationsThepresenceofmeasurablePPIwasfirstdescribedfor children aged 3 and 5 years.111 Between early infancy and 5 years of age, PPI does not appear to regularly exceed 30%, in contrast to adult levels of between 50% and 75%113; some studies have shown nonsignificantPPIintoddlers,114 while others have suggested that longer prepulse intervals are necessary to elicit PPI in preschoolers and infants.115 Baseline startle magnitudes are also smaller in young chil-dren,116whichmayfurtherincreasedifficultyofdetec-tion.Stillotherstudieshavesuggestedperiodswhereprepulsefacilitationismorelikelytobefoundinplaceof PPI117 or PPI may not have been noted at all118 in infants and neonates. Additionally,thesmalldimensionsofinfant’sfacescomplicatethepositioningofEMGsensors.Infantsfrequentlydisplayhighmotoractivity,whichmaycorrupt EMG recordings,119 and they may be unwill-ingtotolerateprocedures,particularlyastheyarefrequentlyfearfulofobjectsbeingpositionedneartheeye.120EvenwithutilizationofminiatureelectrodestomeasureEMG,asignificantnumberofinfantsmayneedtobeexcludedduetolackofidentifiableblinks,fussiness, or crying.121Withtraditionalmethods,at-tritionratesof31%-50%maybeseen;significantlygreater than those typically seen in adult studies, usu-allyaround5%-10%.120

Alternativestotheadult-standardmeasurementofeye blink intensity have been developed for infants. Infants’whole-bodymotorreaction,videoquantifica-tionofinfants’facialmuscularcontractions,andvideoquantificationofeye-blinkintensityhavebeenusedto measure PPI in infants and accurately measure la-tency and intensity of startle.122Inaddition,somelabs

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havesuccessfullyutilizedeye-blinkreflexintensity,successfullycoding91.7%ofacousticstartleprobespresented to 5 month old infants.122Affectivemodula-tionofstartlehasalsobeenquantifiedin5-month-oldinfants,119,123andterm-bornneonateshavealsobeenfoundtoexhibitsignificantPPI.124

Preschoolers/Infants at Risk for Psychiatric IllnessNo studies were found examining PPI in infants or preschoolers known to be at risk of later psychiatric illness.

SummaryDevelopmentalstudiesofPPIareoftencontradictory.SomeauthorssuggestPPIdoesnotdevelopuntil8or9yearsofage,whileothersidentifysomePPIinsome—butnotall—subjects.StillothersreportyoungchildrenhaveprepulsefacilitationratherthanPPI.Itisencouragingthatage-appropriateadaptationsappeartobeavailable.However,theoptimaltaskparam-eters and typical developmental trajectory appear to

remainenigmatic.Untileffectivetaskparameterscanbeidentifiedforyoungchildren,useofPPItostudydevelopmentinat-riskinfantsandpreschoolersmaybe premature.

P50 Sensory GatingP50sensorygatingisanevokedpotentialrecord-ingtaskwhereinanadultparticipantlayssupineinareclined chair with his eyes open while listening to a seriesofpairedauditoryclickswitha500msinter-stimulusinterval;electroencephalographicactivityisrecorded.Cognitiveinhibitionispassivelytestedasthefirststimulusisthoughttoconditionoractivateinhibitory mechanisms that lead to a diminished re-sponsetothesecondstimulus.Sensorygatingissaidtobe“intact”whentheratioofthebrain’sresponsetothesecondclickissignificantlylessthanitsre-sponsetothefirstclick(test/conditioningratioorT/Cratioofsignificantlylessthan1.0).Withintactgating,thefirstclickshould“condition”orprimetheauditorysystem to respond in a diminished way to the second testingstimulus(Figure5).

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Figure 5.ExampleofP50SensoryGating.Inthefirstrow,intactcerebralinhibition(intactP50sensorygating)isillustratedinthattheresponsetothesecondstimulus(upperright)ismuchsmallerthantheresponsetothefirststimulus(upperleft).Onthesecondrow,diminishedcere-bralinhibition(deficientP50)isshowninthattheresponsetothesecondstimulus(lowerright)isveryclosetotheresponsetotheinitialstimulus(lowerleft).Adaptedwithpermission.125

Adult LiteratureAuditorysensorygatingisrelativelyrobustinmosthealthy adults, with a vast majority of the popula-tionshowingmeasurableresponsesuppressiontotheteststimulus(ieT/Cratio<0.50).126,127 Adults with schizophreniahaveanimpairmentinsensorygating,evidencedbylackofattenuationoftheteststimulusresponse,resultinginahigherT/Cratio.6,15,37,128-132 This impairment has also been seen in some individuals at clinical risk of schizophrenia,128particularlyinthosewithafamilyhistoryofschizophreniainafirstdegreerelative.133Deficitsarealsoseeninthosewithschizo-typal personality disorder,134schizoaffectivedisorderbipolar type,135 and in those with bipolar disorder with a history of psychosis.129,135,136

Unaffectedfirst-degreerelativesofthosewithschizo-phrenia and bipolar disorder have also been found toexhibitimpairedP50sensorygating,15,136-138 and heritabilityofP50sensorygatinghasbeenestimatedat 68%.139Inaddition,P50sensorygatinghasap-pearedtohaveavalueinfirst-degreerelativesthatisapproximately halfway between schizophrenia pro-bands and controls, which would be predicted given theirestimationofsharingapproximately50%ofanyabnormal genes related to schizophrenia.138 Other fac-tors such as clinical symptoms,129,135,138antipsychoticuse,129,131,133,135,138andillnessduration131 appear to be less important, though some studies have indicated P50 suppression may be opposed by a subset of secondgenerationantipsychoticmedications,particu-larly clozapine126,140,141 or worsened by increased acute symptomatology.142,143 Smoking has been shown to acutely and transiently normalize P50 suppression in individuals with schizophrenia.144 As such, P50 sensory gatingappearstohavebothstateandtraitlikecom-ponents.Ofnote,P50sensorygatingdeficitshavebeenvalidat-ed in adults with schizophrenia during REM sleep.145 Thisadaptationmaydecreaseresponsevariability

givensensorygating’ssensitivitytostatedependentfactors,particularlyacutestress,146,147andattention148 as during REM sleep noradrenergic neurons central tostressandarousalareinactive.149UtilizingREM,it is possible that decreased stability of P50 record-ingsovertimepreviouslyseen150 may be improved by decreasing state associated variability.145

Child/Adolescent LiteratureThe child literature regarding P50 is somewhat in-consistentwithsomereportsfindingmaturationofthe P50 response by approximately 8 to 10 years of age151,152andothersindicatingmaturationthroughtheend of adolescence.153 It has been suggested that vari-abilitymayberelatedtochangingstate-dependentfactors, as previously described. Adolescentsages14-19yearswithprodromalsymp-tomsofschizophrenia,bothwithandwithoutidenti-fiedhighgeneticrisk,havebeenfoundtohaveanimpairmentinP50sensorygating,154 as have younger childrenages5-10withidentifiedsensoryprocessingdeficits.155 Gender151 and current social withdrawal156 havenotbeenshowntoinfluenceP50recordingsinchildren.

Preschool/Infant AdaptationsThefirstissueonemustaddresswhenconsideringperformingP50sensorygatingininfantsandpre-schoolers is state dependency. As previously noted, P50sensorygatingcanbeaffectedbyacutestress.Asmanyinfantsoftenbecomestressedorupsetwhensubjected to new surroundings or to having elec-trodes placed on their scalps and faces, this issue is of particularimportance.Additionally,movementincreasesartifactsinelec-trophysiologicalrecordings.Adultparticipantscanbeinstructedtoremainstillandnottoblinktheireyes;however,givingverbalinstructionstoinfantsandpreschoolersandexpectingcomplianceisnotpos-sible.Attemptstorestrainyoungchildrenruntheriskofincreasingstress,therebyaffectingsensorygatingby increasing state change that may further, as noted above in adults, decrease the reliability of recordings overtime.For infants and preschoolers, measuring P50 sensory gatingduringREMsleep(termed“ActiveSleep”foryounginfants)isanattractivepossibility.Utilizing

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sleep, a state in which most infants already spend a majorityoftheirtime,oneisabletobypassmove-ment and state dependent concerns. It has been notedthateventhoughP50(measuredduringactivesleep)(1)occursslightlylaterininfants,approxi-mately70msafterthestimulusasopposedtothetraditional50msseeninadults,(2)improveswithageevenwithatimespanofonlymonths,and(3)hasabroadertemporalsignature;inhibitionofthesecondstimulusdoesoccur157 in a reliable fashion.158 Further-more,gatingassessedin14-week-oldchildrenwascorrelatedtotheirgatingat47months,suggestingthatgatingremainsstablethroughoutearlychild-hood.159

Preschoolers/Infants at Risk for Psychiatric IllnessP50sensorygatingduringactivesleephasbeenusedto examine infants of mothers with anxiety as com-pared to infants whose mothers did not have psychi-atric comorbidity, yielding that infants whose mothers experiencedanxietyhadpoorerP50sensorygating,aneffectmitigatedbyanti-depressantuse.160 Infants at higher risk for schizophrenia secondary to having parentswithpsychosis,comparedtonon-smokingmothers without psychiatric illness, have decreased inhibitorygatingutilizingtheP50paradigm.161 Im-provedinfantP50sensorygatingdevelopmentisalsoassociatedwithperinatalcholinesupplementation.162

SummaryP50sensorygatingappearstobethetaskthat,thusfar,hasbeenthemosttranslatedandutilizedinyoungerpopulationsatriskofdisease.Inadultsand adolescents, the task has been more rigorously defined,hasbeenassociatedwithpsychosis,anditsgeneticriskhasbeenmoreclearlydelineated.Itisinterestingtonotehowthisconsensusoccurred.Throughmeta-analysis,itwasdeterminedthatthereisarelationshipbetweenstimulusintensityandtheeffectsizebetweenindividualswithschizophreniaandcomparison subjects.137Withlargermulti-sitetrials,aunifiedprotocolincludinglowersoundintensity,subjectsplacedinarecumbentposition,andabetatogamma(10-100hz)EEGfrequencyband-passfilter,aresolutionofsitedifferenceswasabletooccur.Itmaybe that similar data review in other tasks will lead to unificationofapparentdiscrepanciesthusfarseeninyounger age groups.

Thefindingsthatstateassociatedfeaturesmaybereduced by recording during REM sleep makes this taskparticularlyattractiveforuseininfants.Assuch,it has been successfully used in infants of mothers with mood and anxiety disorders and infants of par-ents with psychosis. It is clear that infant research is possible.Itwouldbeinterestingtocontinuetoextendthesefindingstoolderagegroupsandtofollowthechange in symptomatology associated with impaired P50sensorygatingovertime.Forexample,ithasbeenshownthatimpairedP50sensorygatingasaninfanthasbeenassociatedwithmoreattentionalproblems at age 3.3 years as measured by the child behavior checklist.163

DiscussionMost neuropsychiatric disorders are presumed to be neurodevelopmental in nature, where onset of symptomsistheendresultofadecades-longinter-actionbetweengeneticandenvironmentalfactors.Thereare2presumedcriticaldevelopmentalwin-dowsrelativeforpsychosis:prenatalandadolescent.Abnormalitiesinprenatalbraindevelopmentleadtovulnerability and, in some individuals with already vulnerablebrains,furtherabnormalitiesinadolescentbrain development result in conversion from vulner-ability to illness.1,2 One of the major corollaries of this hypothesisisthatwhileonsetofmorespecificandsevereillnesses,suchaspsychoticillnesses,requiresadversedevelopmentduringbothcriticaldevelop-mental windows, abnormal development during the prenatal window alone increases lifelong risk for significantothertypesofcognitiveandfunctionalimpairmentincludingattentionalandsocialdysfunc-tion,evenifthelateradolescentimpairmentinbraindevelopment never occurs.164-170Another way of say-ing this is that abnormal prenatal neurodevelopment non-specificallyincreasesriskforawiderangeofneuropsychiatricandcognitivedisorders.Thissome-timesleadstotheconcernthatnon-specificityofrisklimitsthepotentialbenefitofearlyuseofbiomarkers.However,non-specificityalsoprovidesanopportunityforunderstandingand,withintervention,preventionacross a breadth of disorders. The malleability of the brain during early developmental period makes it a potentiallyidealtimetointervene,withinterventionlastingonlyafewmonthshavingpotentiallife-longramifications.

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Anotherrelatedpotentialriskofearlydevelopmentalbiomarkers is the risk that what appears to be the samemeasure(egdisruptionofsmoothpursuit)atdifferentagesmaynotreflectthesameneurobiology.Thus, longitudinal approaches and converging evi-denceacrossdifferentstudyformatsareanecessarysteptowardsaccurateinterpretationofearlydevelop-mental biomarkers.TheNationalInstituteofMentalHealthhascalledforan increase in research focusing on the developmen-tal aspects of biological markers, and this review high-lightstherelativelackofresearchinthisarea.Severalpsychophysiological tasks are, in older children and adolescents, associated with an increased risk of later onset illness, and some of the tasks appear to be ready for research use in infants and preschoolers. P50sensorygatingandsmoothpursuiteyemove-mentsalreadyhaveearlyliteraturesuggestingtheir

utilityinveryyoungpopulations.Theantisaccadetaskandprepulseinhibitionmayalsohaveutility,althoughfurtherworkadaptingmethodologytoyoungchildrenisnecessary(Figure6).

ConclusionThechargetoinvestigatethedevelopmentofpsy-chiatricdiseasethroughoutthelifespanmayinitiallysoundintimidating.Workingwithinfantsandpre-schoolers means more variability, and with more variability(andfrequentlylowerorsmallerresponsesandrates),anincreasedcapacitytodetectdifferencesmust be present. Before undertaking this task, one wouldfirstwanttoensurethatdeficitsarepresent,have been associated with risk of later onset disease, have developmentally appropriate correlates, and the tasksutilizedinolderpopulationsareusableinpre-

Figure 6.Graphicrepresentationoftaskconclusions.AsillustratedwithanX,theantisaccade,prepulseinhibition,P50sensorygating,andsmoothpursuiteyemovement(SPEM)tasksallhavebeenassociatedwithriskoflateronsetdisease,areheritable,andhavedevelopmentallyappropriateversionsavailableforuseininfantsandpreschoolers.Antisaccade,P50,andsmoothpursuitfurtherappeartohavedevelopmentalandspecifictaskparametersmoredefined,andP50andSPEMhavealsoseensomepreliminaryresearchdoneinpopulationsatriskofdevelopingpsychiatricdiseaseusingadaptations.

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schoolers and infants. In several of the tasks described above, we believe that this is the case.Historically,investigatorshavealsobeenhesitanttoperform research on infants and young children be-causeoflackofspecificityregardingdiseaseoutcome.The NIMH’s proposal for novel ways to approach psy-chiatric disease diminishes these concerns.

If we are to decrease morbidity and mortality associ-ated with risk factors for psychiatric disease and begin toconsiderprimarypreventionofpsychiatricillness,research in younger age groups including infants and preschoolersisofparamountimportance.Utilizingadaptationsoftraditionaladulttasks,thisresearchisalso now possible.

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132. Sánchez-MorlaEM,SantosJL,AparicioA,García-JiménezM,SoriaC,ArangoC.NeuropsychologicalcorrelatesofP50sensorygatinginpa-tientswithschizophrenia.Schizophr Res.2013;143(1):102-106.

133. CadenheadKS,LightGA,ShaferKM,BraffDL.P50suppressioninindividualsatriskforschizophrenia:theconvergenceofclinical,familial,and vulnerability marker risk assessment. Biol Psychiatry.2005;57(12):1504-1509.

134. CadenheadKS,LightGA,GeyerMA,BraffDL.SensorygatingdeficitsassessedbytheP50event-relatedpotentialinsubjectswithschizotypalpersonality disorder. Am J Psychiatry.2000;157(1):55-59.

135. OlincyA,MartinL.DiminishedsuppressionoftheP50auditoryevokedpotentialinbipolardisordersubjectswithahistoryofpsychosis.Am J Psychiatry.2005;162(1):43-49.

136. SchulzeKK,HallMH,McDonaldC,etal.P50auditoryevokedpotentialsuppressioninbipolardisorderpatientswithpsychoticfeaturesandtheirunaffectedrelatives.Biol Psychiatry.2007;62(2):121-128.

137. deWildeOM,BourLJ,DingemansPM,KoelmanJH,LinszenDH.Ameta-analysisofP50studiesinpatientswithschizophreniaandrelatives:differencesinmethodologybetweenresearchgroups.Schizophr Res.2007;97(1-3):137-151.

138. OlincyA,BraffDL,AdlerLE,etal.InhibitionoftheP50cerebralevokedresponsetorepeatedauditorystimuli:resultsfromtheConsortiumonGeneticsofSchizophrenia.Schizophr Res.2010;119(1-3):175-182.

139. HallMH,SchulzeK,RijsdijkF,etal.HeritabilityandreliabilityofP300,P50anddurationmismatchnegativity.Behavior genetics. 2006;36(6):845-857.

140. NagamotoHT,AdlerLE,HeaRA,GriffithJM,McRaeKA,FreedmanR.GatingofauditoryP50inschizophrenics:uniqueeffectsofclozapine.Biol Psychiatry.1996;40(3):181-188.

141. LightGA,GeyerMA,ClementzBA,CadenheadKS,BraffDL.NormalP50suppressioninschizophreniapatientstreatedwithatypicalantipsy-choticmedications.Am J Psychiatry.2000;157(5):767-771.

142. FranksRD,AdlerLE,WaldoMC,AlpertJ,FreedmanR.Neurophysiologicalstudiesofsensorygatinginmania:comparisonwithschizophre-nia. Biol Psychiatry.1983;18(9):989-1005.

143. BakerN,AdlerLE,FranksRD,etal.Neurophysiologicalassessmentofsensorygatinginpsychiatricinpatients:comparisonbetweenschizo-phrenia and other diagnoses. Biol Psychiatry.1987;22(5):603-617.

144. AdlerLE,HofferLD,WiserA,FreedmanR.Normalizationofauditoryphysiologybycigarettesmokinginschizophrenicpatients.Am J Psy-chiatry.1993;150(12):1856-1861.

145. KisleyMA,OlincyA,RobbinsE,etal.SensorygatingimpairmentassociatedwithschizophreniapersistsintoREMsleep.Psychophysiology. 2003;40(1):29-38.

146. WhitePM,YeeCM.EffectsofattentionalandstressormanipulationsontheP50gatingresponse.Psychophysiology.1997;34(6):703-711.147. JohnsonMR,AdlerLE.TransientimpairmentinP50auditorysensorygatinginducedbyacold-pressortest.Biol Psychiatry.1993;33(5):380-

387.148. YeeCM,WilliamsTJ,WhitePM,NuechterleinKH,AmesD,SubotnikKL.AttentionalmodulationoftheP50suppressiondeficitinrecent-

onset and chronic schizophrenia. J Abnorm Psychol.2010;119(1):31-39.149. HobsonJA,McCarleyRW,WyzinskiPW.Sleepcycleoscillation:reciprocaldischargebytwobrainstemneuronalgroups.Science.

1975;189(4196):55-58.150. LightGA,SwerdlowNR,RisslingAJ,etal.Characterizationofneurophysiologicandneurocognitivebiomarkersforuseingenomicandclinical

outcome studies of schizophrenia. PLoS One.2012;7(7):e39434.151. BrinkmanMJ,StauderJE.DevelopmentandgenderintheP50paradigm.Clin Neurophysiol.2007;118(7):1517-1524.

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152. Myles-WorsleyM,CoonH,ByerleyW,WaldoM,YoungD,FreedmanR.DevelopmentalandgeneticinfluencesontheP50sensorygatingphenotype. Biological Psychiatry.1996;39(4):289-295.

153. FreedmanR,AdlerLE,WaldoM.Gatingoftheauditoryevokedpotentialinchildrenandadults.Psychophysiology.1987;24(2):223-227.154. Myles-WorsleyM,OrdL,BlailesF,NgiralmauH,FreedmanR.P50sensorygatinginadolescentsfromapacificislandisolatewithelevated

risk for schizophrenia. Biol Psychiatry.2004;55(7):663-667.155. DaviesPL,ChangWP,GavinWJ.Maturationofsensorygatingperformanceinchildrenwithandwithoutsensoryprocessingdisorders.Int J

Psychophysiol.2009;72(2):187-197.156. MarshallPJ,Bar-HaimY,FoxNA.ThedevelopmentofP50suppressionintheauditoryevent-relatedpotential.Int J Psychophysiol.

2004;51(2):135-141.157. KisleyMA,PolkSD,RossRG,LevisohnPM,FreedmanR.Earlypostnataldevelopmentofsensorygating.Neuroreport.2003;14(5):693-697.158. HunterSK,CorralN,PonicsanH,RossRG.ReliabilityofP50auditorysensorygatingmeasuresininfantsduringactivesleep.Neuroreport.

2008;19(1):79-82.159. GillowS,HunterS,RossR.StabilityofP50sensorygatinginpreschoolers(abstract).Journal of Investigative Medicine.2010;58:154-155.160. HunterSK,MendozaJH,D’AnnaK,etal.Antidepressantsmaymitigatetheeffectsofprenatalmaternalanxietyoninfantauditorysensory

gating.Am J Psychiatry.2012;169(6):616-624.161. HunterSK,KisleyMA,McCarthyL,FreedmanR,RossRG.Diminishedcerebralinhibitioninneonatesassociatedwithriskfactorsforschizo-

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Human Development.2010;41(5):479-489.164. CornblattBA,MalhotraAK.Impairedattentionasanendophenotypeformoleculargeneticstudiesofschizophrenia.American Journal of

Medical Genetics.2001;105(1):11-15.165. DworkinRH,LewisJA,CornblattBA,Erlenmeyer-KimlingL.Socialcompetencedeficitsinadolescentsatriskforschizophrenia.Journal of

Nervous and Mental Disease.1994;182(2):103-108.166. SeidmanLJ,GiulianoAJ,SmithCW,etal.Neuropsychologicalfunctioninginadolescentsandyoungadultsatgeneticriskforschizophrenia

andaffectivepsychoses:resultsfromtheHarvardandHillsideAdolescentHighRiskStudies.Schizophrenia Bulletin.2006;32(3):507-524.167. LinA,WoodSJ,NelsonB,etal.Neurocognitivepredictorsoffunctionaloutcometwoto13yearsafteridentificationasultra-highriskfor

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2001;50(1-2):123-131.

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SleepSpindlesandAuditorySensoryGating:Two MeasuresofCerebralInhibitioninPreschool-Aged

Children are Strongly Correlated

At any moment, a vast amount of sensory infor-mationisbeingcapturedbyperipheralmodali-

tiesandhasthepotentialtoreachthecerebralcortex, where it can be processed and acted upon. Muchofthisinformationisextraneous,andthusre-ducing(“gating”)transmissionofirrelevantsensoryinformationisnecessaryinordertoavoidoverbur-deningcorticalprocessingcapabilities.Thisispartic-ularlytrueduringsleep,wherecorticalprocessingofexternalstimulihastobelimitedtothemostcriticalsensoryinformation.Whilesensorygatingoccursduringmultiplestagesofsleep,therehasbeenlittleefforttoexplorecorrelationsbetweengatingacrossstages:doessensorygatingabilityatonestageofsleeppredictsensorygatingduringanotherstage?Acorrelationbetweendifferentgatingmechanismswould suggest overlapping neural mechanisms of gatingandprovidesupportforexploringcommonetiologicfactors.Wefocushereon2sensorygatingprocesses that are both thought to include thalamic

interneurons,1,2butwhichareprevalentatdiffer-entsleepstages:sleepspindlegeneration,whichislimitedtoStage2non-RapidEyeMovement(NREM)sleep;andP50sensorygating,whichismaximallyeffectivewhileawakeandduringRapidEyeMove-ment(REM)sleep.Asampleofconvenienceofover-nightelectroencephalogramsfromhealthy4-year-oldswasutilizedinthisinitialstudy.Sleepspindlesarecharacteristicbrief11-15Hzwaveforms on EEG with a progressively increasing thendecreasingamplitudethatarespecifictothesleeping state.3 They are generated by GABAergic neuronsinthethalamicreticularnucleus(TRN)4 and arebelievedtoreflectneuronalconnectivitypat-ternsincorticothalamicandthalamocorticalcir-cuits.3,5NinetypercentofTRNneuronalprojectionsaretothalamocorticalneurons;activationofTRNneurons inhibits signal transmission to the cerebral cortex.6Thisthalamicspindleproductionbycortex-

Peng-Peng Wei, MD; Sharon K. Hunter, PhD; Randal G. Ross, MD*

AbstractIntroduction.SleepspindlesandP50sensorygatingarebothreflectiveofcerebralinhibition,however,aredifferentiallyactiveduringdifferentphasesofsleep.AssessingwhethersleepspindlesandP50sensorygat-ingcorrelateisafirststeptoevaluatewhetherthese2formsofcerebralinhibitionreflectoverlappingneuralcircuits. Methods.EEGdatawerecollectedbetweenmidnightand6:00AMon13healthypreschool-agedchildren.P50sensorygating,calculatedduringREMsleep,negativelycorrelatedwithspindleduration(r=-.715,p=.006)andinter-peakdensity(r=.744,p=.004).TherewasatrendtowardhigherS2/S1ratiosbeingassociatedwithfewerpeaksperspindle(r=-.546,p=.053).In4-year-olds,2establishedphysiologicalmeasuresofsensorygatingandarecorrelateddespitebeingmaximallyactiveduringdifferentstagesofsleep.Conclusions.Theseresultssuggestthereisanoverlapinbrainmechanismsunderlyingeachgatingmechanism.

*Author Affiliations: Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine, Pediatric Men-tal Health Institute, Children’s Hospital Colorado. Dr Wei is currently at New York Presbyterian Hospital, New York, New York. Dr Hunter is currently residing in Houston, TX.

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stimulatedreticularcellsgatessensoryinputwhilesleeping, allowing the brain to resist waking in the faceofdisruptiveexternalsensorystimuli.7, 8 P50auditorysensorygatingreferstoareductioninanearlyevokedresponseinthefaceofrepetitionofanauditorystimulus.Inthemostcommonlyutilizedform of the task, an individual is exposed to 2 iden-ticalauditorystimulioccurring500msapart.Theamplitude of early components of the evoked re-sponseisreducedinresponsetothesecondstimulusrelativetothefirst.9Onecommonquantificationofthiseffectistomeasuretheratiooftheamplitudesofthe P1 wave, which in adults occurs approximately 50 msafterboththefirst(S1)andsecond(S2)stimulus.Intactauditorysensorygatingisindicatedbyareduc-tionintheamplitudeoftheevokedP1wavetothesecondstimulusthatyieldsaratiosignificantlylessthan1.P50sensorygating(ratioscloserto0)occursduringREMsleepbutisabsent(ratioscloserto1)inNREM sleep.10P50sensorygatingcanbeidentifiedinnewborns11 and appears to be fully developed within afewmonthsafterbirth.12P50sensorygatinghasbeen linked to GABAergic neurons13, 14 and involves a circuit which includes the thalamus, hippocampus, and prefrontal cortex.2

Sleep spindles have been found to mediate sleep maintenance,15memoryconsolidation,4,8,16-19 and cor-ticaldevelopmentduringsleep,5 among other func-tions,andreducedspindleactivityisthoughttobeareflectionofinherentthalamicdysfunctionaswellasthalamicresponsivenesstocorticalstimulation.Poorsleepspindlegenerationin5-year-oldspredictsmore externalizing behavior and more peer prob-lems 1 year later.20 In a similar fashion, poor auditory sensorygatingininfantshasbeenassociatedwithlaterproblemsinattention,anxiety,andexternaliz-ing symptoms at 40 months of age,21 and it has been postulatedthatdiminishedsensorygatingininfantsmayreflectanincreasedriskforlaterpsychopathol-ogy.22-24 fMRI studies also suggest that the thalamus is involvedinsensorygating.2,25 For both sleep spindles andP50sensorygating,thethalamicreticularnucleusis thought to be responsible for the thalamic response duringthegatingtasks,2,6,19wheredysfunctioninGA-BAergic neurotransmission leads to impaired sensory inhibition.4,13,14

SleepspindlesandP50sensorygatingareboththoughttoreflectactivityofGABAergicneuronsand

are also both thought to involve the thalamus, yet the2measuresreflectactivityduringdifferentsleepstages(Stage2forsleepspindlesandREMforP50gating).Thisraisesthequestionofwhetherornotthe 2 inhibitory processes are correlated—we hy-pothesize that they are. We have previously reported onovernightP50sensorygatingscoresin4-year-oldchildren as part of a process to determine stability betweeninfantand4-year-oldperformanceduringREM sleep. That study suggested that P50 sensory gatingmaturedtoadultlevelswithinafewmonthsafterbirthandthatanalysisof4-year-oldresultsmaybe generalizable to other ages.26 The current study adds an analysis of sleep spindles during the same overnightrecordingwiththegoalofinvestigatingtherelationshipbetween2measuresofcerebralinhibi-tion,sleepspindlesandP50auditorysensorygating.Thisisthefirststudytoinvestigatesucharelationshipandwouldcontributetotheefforttounderstandtherelationshipbetweensensorygatingmechanisms.

Method

ParticipantsFourteenpreschool-agedchildren(9females)whowere part of a longitudinal study on early child devel-opment in a large metropolitan area and who were within 2 weeks of their fourth birthday were recruited foranovernightsleepstudyaimedattestingP50au-ditorysensorygatingstabilityfrombirthto4yearsofage.Artifact-freedatawithminimumsof30minutesof REM and 3.5 hours of total sleep was considered the minimum amount necessary for analysis. Data from1participant(1female)isexcludedbecausetherewasinsufficientartifact-freedata.Themeanagefortheremainingparticipantsinthisstudyis47.15(SD=0.99)months.Additionaldemographicinforma-tionissummarizedinTable1.Thiswasahealthypedi-atric sample, which had been followed since infancy.

ProcedureAll procedures involving human subjects were ap-provedbytheColoradoMultipleInstituteReviewBoard(COMIRB),andparentsoftheparticipantsgavewritteninformedconsent.Participantswereadmittedfor an overnight stay to a pediatric clinical research centeratalocalchildren’shospital.Allparticipantswere screened prior to admission for acute illness,

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andonceadmittingprocedureswerecomplete,wereprovideddinnerandaccesstoentertainmentuntilbedtime.Parentsofparticipantswereencouragedtofollowthechild’stypicalbedtimeroutine.Oneparentremained in the room with the child overnight.

Electroencephalographic RecordingsAg/AgClelectrodes(Grass;WestWarwick,RhodeIsland,USA)filledwithTen20conductivepaste(DOWeaver;Aurora,Colorado,USA)wereattachedtothesleeping child with adhesive medical tape. EEG and auditory-evokedpotentialswererecordedfromthevertexofthescalp(Cz).Foraidinsleepstaging,bipo-larelectrooculogram(EOG)wasrecordedfromelec-trodesdirectlysuperiorandlateraltoeithertheleftorrighteye;submentalelectromyogram(EMG)wasalso recorded. Times of movement and environmental events were also noted. Signals were recorded using NuAmps(NeuroscanLabs,Sterling,Virginia,USA).EEGsignalswereamplified5000timesandfilteredbetween0.05and100Hz;EOGsignalswereamplified1000timesandfilteredbetween1and200Hz;andEMGsignalswereamplified10,000timesandfilteredbetween 1 and 200 Hz. Sampling rate occurred at 1000Hz.Stimuluspresentation(forassessmentofP50auditorysensorygating)andrecordingbeganwhentheelectrodeimpedanceswerebelow10kΩ.ThelongestperiodsofREM(thestageforthereliableassessmentofP50sensorygating)andStage2(theperiodmostassociatedwithsleepspindleactivity)sleep occur in the early morning hours; thus, data collectiondidnotbeginuntil11:00PMandcontinueduntilapproximately6:00AM.ThedatawereconvertedfromtheScan4.1software(NeuroscanLabs;Sterling,Virginia,USA)formattoASCIIformatsothatfurtheranalysisusingMatLab(Mathworks;Natick,Massachusetts,USA)softwarecouldbeconducted.AvisualrepresentationofEOG,EMG,andEEGactivitywasgeneratedandprovidedaglobalviewofeachparticipant’ssleepcycles(Fig-ure1A).Sleepstagingwascompletedbasedonthecriteria of Anders et al.26REMsleepwasidentifiedbythe presence of rapid eye movements obtained on EOG, low amplitude in the EMG, and low amplitude highfrequencyintheEEG.Stage2NREMsleepwasidentifiedbytheabsenceofrapideyemovementsasobtained by EOG, increased amplitude in the EMG, and the presence of sleep spindles. Sleep state was

thenverifiedbyvisualinspectionofthecontinuousrecordingin20-sepochs.

Sleep Spindle Analysis Spindledetectionwasperformedbyapplyingaband-passfilterbetween11-15Hz.Abaselineaverageamplitudewascalculatedfromspindle-freeEEGandathresholdvalueof2.5timesthebaselineaveragewasusedforautomatedidentificationofspindlecycles.Likewise,thebeginningandendofeachspindlewasdetermined by an increasing or decreasing peak am-plitudethatfellbelow2.5timesthebaselineaverage.Automatedselectionwasconfirmedbyvisualinspec-tionoftheEEGrecord(Figure1B).Measurementsofspindledurationinmillisecondsandthenumberofindividual peaks per spindle were obtained. Mean inter-peakinterval(calculatedasnumberofpeaksperspindledividedbyspindleduration)wasusedasameasure of spindle density. Spindles occur as a series of electroencephalographic peaks; more peaks per spindle,alongerspindleduration,andalowerinter-peakinterval(greaterdensityofpeaks)areevidenceofincreasedspindleactivityandreflectincreasedsensorygating.

P50 Auditory Sensory Gating AnalysisMethodsforP50sensorygatingassessmentinchil-dren have been previously described in detail,12 andwillbrieflybereviewedhere.Pairedclickswerepresentedthrough2speakerspositionedoneitherside of the bed at a distance of .50 m from each ear. Volumewasadjustedsothateachclickwasat85-dBsound pressure level at the ear. The clicks were de-liveredcontinuouslythroughouttheovernightstudyforeachsubject.Thefirst20minutesofthelongest-recorded REM cycle was used for analyses. This length oftimewasselectedbecauseityieldsanadequatenumberofstimuliforanalysisandreducesvariabilitycausedbyindividualdifferencesinsleep.27 Single-trial-evokedpotentialswereextractedfrom100 ms before each click to 200 ms following each click. Trials were excluded in which the signal on the recordingofidentifiedperiodsexceeded±75mV.Theaverage waveforms from single trials were band pass filteredbetween10and50Hztoaccentuatemiddlelatency components. For each subject, the largest positivepeakbetween50and100msafteranaudi-toryclick(P50)precededbyanegativetroughwas

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Figure 1.(A)Graphicalrepresentationofa5-hoursampledrawnfromovernightEEG,EOG,andEMGactivityrecordedfromaparticipant.AperiodofREMhasbeenhighlightedtoshowincreasedEOGactivityanddecreasedEMGandEEGspindleactivityindicativeofthisstageofsleep.AperiodofStage2NREMactivityhasbeenhighlightedtodemonstrateincreasedspindleactivityintheEEGaccompaniedbydecreasedEOGactivity.(B)Anexampleofasleepspindlerecordedfromthevertex.Thisimageisrepresentativeofspindleactivityfollowingtheapplicationofan11-15Hzbandpassfilter.Thisparticularspindlehad6peakswithameaninter-peakintervalof73.33ms.(C)P50-evokedpotentialtracings.Twostimuliarepresented500msapart(notedbythe2time0sinanyhorizontalpairofpanels).TheP50responseisdelin-eatedbyhashmarks.Intactsensorygatingisdemonstratedonthetophalfofthisfigure.Notethesizeoftheevokedresponsetothefirststimulus,S1(1.86µv)andthecorrespondingresponsetothesecondstimulus,S2(.11µv).TheresultingS2/S1ratiois0.06.PoorP50sensorygatingisdemonstratedonthebottomhalfofthisfigure.Theamplitudeoftheresponsetothefirststimulus,S1was1.64µvwhilethatforS2was1.05µv.TheresultingS2/S1ratiois0.64.

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identifiedandmeasured,peaktotrough,byacom-puter algorithm.For each child, a mean response latency and ampli-tudeoftheP1-evokedpotentialwavetoeachstimu-lus(S1andS2)werecalculated.Inaddition,theirratiowascalculatedbydividingtheamplitudeoftheP1-evokedresponsetoS2bytheamplitudeoftheP1-evokedresponseevokedbyS1.Aratiocloserto0isindicativeofrobustsensorygating,whilearatiocloserto1isindicativeofdiminishedsensorygating(Figure1C).

Statistical ApproachDescriptivedatawascalculatedforspindlemeasures(durationanddensity)andP50auditorysensorymeasures(amplitudes,latencies,andgatingratio).Bivariatecorrelationalanalyseswereusedtoassesstherelationshipbetweenspindleduration,numberofpeaks per spindle, and spindle density and measures ofP50auditorysensorygating.IBMSPSSStatisticsforWindows,Version22(Released2013,Armonk,NY:IBMCorp.)wasusedforallanalyses.

Results Themeanlengthofartifact-freesleepdatawas4.76(SD=.64)hours(Range:4.06–5.96hours).ThemeanlengthofREMsleepdatawas57.77(SD8.96)minutes(Range44-69minutes).Table1summarizesthepri-mary electrophysiological measures of interest.P50gatingratioswerepositivelycorrelatedwithspindledensity(r=.744,p=.004),negativelycorrelatedwithspindleduration(r=-.715,p=.006)andtrended

towardsanegativecorrelationwithmeaninter-peakinterval(r=-.546,p=.053)(Table2andFigure2).

DiscussionOneofthebrain’smostimportantfunctionsistoinhibititsownsignalsinordertofilteroutirrelevantsensoryinformation.Itutilizesanumberofmecha-nisms to achieve this goal including 2 processes activeduringsleep:sleepspindlegenerationandP50sensorygating.WhilethalamicGABAergicinhibitionhas been postulated to contribute to both inhibitory mechanisms,therehasbeenlittleinvestigationofwhether performance of one process correlates to the other.Inthisstudy,weexaminedtherelationship,inpreschool-agechildren,between2measuresofce-rebralinhibitoryfunctioningthathadnotbeencom-paredbefore,P50sensorygatingandsleepspindles.ElevatedP50gatingratios,correspondingtoimpairedauditorygating,wereassociatedwithshorterspindledurationaswellasincreasedintra-spindledensity(lowermeaninter-peakinterval).P50sensorygatingandsleepspindlesaremaximallyactiveatdifferentstagesofsleep,suggesting,onthesurface,thattheyaretheproductofdifferentneuro-logicalcircuits.However,ourresultsdemonstratingthecorrelationbetweentheprocessesaremorecon-sistent with the hypothesis that GABAergic thalamic interneurons contribute to both processes. As the TRNfunctionsasthespindlepacemaker,withspindlerhythmpersistingindecorticatedanimalsbutdisap-pearingafterthalamicdestruction,5 both intrinsic thalamiccellsandtheirconnectionstoandfromthecortexareimplicatedindiminishedgating.

Figure 2.ScatterplotshowingcorrelationofP50ratio(S2/S1)and(A)meanspindleduration(r=-.715,p=.006),(B)numberofpeaksperspindlecycle(r=-.546,p=.053),and(C)meaninter-spindleinterval(intra-spindledensity)(r=-.728,p=.005).

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Analternativemethodforexamininginterrelation-shipsbetweenthese2sleep-associatedgatingmecha-nisms would have been to focus on individuals with deficienciesincognitivefunctionsthathaveprevi-ously been associated with abnormal sleep spindles andP50measurements,includingattention,executivefunctioning,andworkingmemory.These2sensorygatingdeficitsarepresentinarangeofneurodevel-opmental disorders including schizophrenia,7,9,16,19,28-30 autismspectrumdisorders,31-33 and ADHD.34 How-ever,evenifacorrelationbetweenthese2physi-ologic measures had previously been elucidated in neuropsychiatrically-illsubjects,itwouldbedifficultto interpret the results. It would be unclear whether these measurements would correlate due to overlap-pingfunctionalcircuitsorwhetherthecorrelationwasaresultofsimilareffectsonbothprocessesduetomedicationtreatmentorcognitivesequelaeofthedisease.P50sensorygatingmaturestoadultlevelswithinafewmonthsafterbirth27andisstableafterthat point.26Spindleactivityalsoisrelativelystable,atleastfromlatepreschoolyearsthroughmid-adoles-cence.35Thus,althoughthepediatricpopulationin-vestigatedinthisstudywasasampleofconvenience,generalizabilitytoolderpopulationsmaybereason-able.Inaddition,anadvantageofstudyingyoungchildren is the ability to study processes prior to onset oftreatmentandpriortotheeffectsofyearsofhav-ing to live with the disease. Establishing that these 2 measures represent the same underlying pathology may guide future studies in clarifying the mechanism behind these faulty inhibitory brain processes.While not the primary purpose of this report, an importantgoalintheinvestigationofinhibitorypro-cessescouldbetocontributetotheidentificationofbiophysiological risk factors for neurodevelopmental disorders.LowerspindleactivityandpoorP50senso-rygatingeacharepredictiveofbothlaterneurocog-nitiveandbehavioraldifficulties.20,21 If sleep spindles

andP50auditorygatingareindeedcorrelatedandrepresent the same underlying pathology as our re-sultssuggest,concurrentevaluationsofbothprocess-esmayprovidebetterpredictiveabilitythaneitherassessmentalone.Futureresearchwouldberequiredtoassessthispossibility.Inaddition,asthisstudywasdone only in young children, future research may also investigatetheeffectofageonthecorrelationbe-tweensleepspindlesandauditorygating.

ConclusionP50sensorygatingandsleepspindlebothfunctiontogatesensoryinformation;however,duringsleep,spindlegenerationisstrongestduringStage2slowwavesleep,whileP50sensorygatingismostactiveduringREMsleep.ThecorrelationbetweenP50gat-ingratiosandsleepspindles,2physiologicalmeasuresofsensorygating,suggestthat,despitethefactthatthe2measuresoccurduringdifferentstagesofsleep,these 2 processes may share some underlying neuro-circuitry. GABAergic thalamic neurons are one pos-sible contributor to both processes.

Author NoteEachauthornotesnoconflictsofinterest.ThisworkwassupportedbyUnitedStatesPublicHealthService(USPHS)GrantsMH056539,RR025780,MH080859,MH086383,HD058033,TR000154,theInstituteforChildrens Mental Disorders, and the Anschutz Family Foundation.WealsowishtoacknowledgetheUniver-sity of Colorado School of Medicine Research Track and provide a special thank you to the families who participatedinthisstudy.Address correspondence to: Randal G. Ross MD, De-partmentofPsychiatry,SchoolofMedicine,Universityof Colorado Denver, 13001 E. 17th Place, Campus Box F546,Aurora,CO80045,[email protected].

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Table 1.Demographics,Spindle,andP50Characteristics

Demographics N (%)Female:male 8:5(62:38)Caucasian Hispanic 2(15)CaucasianNon-Hispanic 11(85)

Mean (SD)MaternalSocioeconomicStatus(SEI)a 55.38(26.79)Age(months) 47.15(.99)Spindle Characteristics Mean (SD)SpindleDuration 838(144)msecNumber of peaks per spindle 11.5(1.75)Inter-peakinterval 72.65(4.19)msecP50 Characteristics Mean (SD)

S2(test)amplitude 1.39(1.04)µVS1(conditioning)amplitude 2.58(1.36)µVS2/S1ratio 0.534(0.297)S2 latency 67.31(7.94)msecS1 latency 64.2(8.03)msec

aTheSocio-economicIndex(SEI)ofOccupations36includes503occupationsscoredinapotentialrangeof0-100.Mana-gerialandprofessionaloccupationsgenerallyhavescoresabove60;technical,sales,andadministrativesupportoc-cupationsgenerallyscorebetween35and60;service,agricultural,andlaboroccupationsgenerallyhavescoresbelow35;neveremployedsingleindividualsareassignedascoreof0.Valuesreportedareforthehighestoccupationvalueachieved across an individual’s life.

Table 2.CorrelationsbetweenP50componentsandspindlecharacteristics S1,FirststimulusinP50measure;S2,SecondstimulusinP50measurep<.05

SpindleDuration Number of peaks per spindle cycle

Inter-peakinterval(Intra-spindledensity)

Pearson Correlation(r)

Significance(p) Pearson Correlation(r)

Significance(p) Pearson Correlation(r)

Significance(p)

S1 amplitude

-.044 .885 -.134 .662 .195 .524

S2 amplitude

-.484 .094 -.424 .149 -.364 .221

S1 latency -.201 .511 -.286 .343 .147 .631S2 latency .226 .458 .177 .562 .162 .596P50ratio(S2/S1)

-.715 .006a -.546 .053 -.728 .005a

82


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84

Contributors

Julia Barnes, PhD; Author

JuliaBarnes,PhDisaseniorinstructorintheDepart-mentofPsychiatryattheUniversityofColoradoSchool of Medicine and serves as a psychologist in the PediatricMentalHealthInstitute(PMHI)atChildren’sHospital Colorado. Dr Barnes is responsible for provid-ingbehavioralandcognitive-behavioraltherapy(CBT)tochildrenwithAutismSpectrumDisorder(ASD)and other Intellectual and Developmental Disabili-ties(IDD)atmultiplelevelsofcare.SheservesinthePMHIoutpatientclinicandtheinpatientandpartialhospitalizationprogramsoftheNeuropsychiatricSpecialCareUnit.DrBarnesprovidesbothdirectCBTservices to children and behavioral training to caregiv-ers to treat a variety of severe behavior problems and othersymptomsofco-occurringpsychiatricconditionsincluding anxiety disorders and mood disorders. Dr Barnesalsoadministratesandco-leadsstafftraininginitiativesontheNSCprogramandprovidestraineesupervision. Dr Barnes’ scholarly interests relate to evidence-basedstaffandcaregivertraining,aswellasmitigatingtheimpactofstressoncaregiversofchil-dren with ASD/ IDDs.Dr Barnes received her bachelor’s degree in Psychol-ogyfromtheUniversityofRochesterandherdoctoraldegreeinClinicalPsychologyfromBinghamtonUni-versity(SUNYBinghamton).Shecompletedapred-octoral internship in intellectual and developmental disabilitiesatNationwideChildren’sHospitalandapostdoctoral fellowship on the Neuropsychiatric Spe-cialCareUnitatChildren’sHospitalColorado.

Cindy Buchanan, PhD; Author Cindy Buchanan, PhD is an assistant professor in the Departments of Psychiatry and Pediatric Surgery at theUniversityofColoradoSchoolofMedicine.Sheserves as the Pediatric Psychologist for the Pediatric Transplant,PediatricUrology,andBowelManage-ment programs at Children’s Hospital Colorado. Dr Buchananiscurrentlyinvestigatinginterventionsthatworktoimproveadherencetomedicationregimensforpediatrictransplantpatients.Additionally,sheis

investigatingtherelationshipbetweencoping,familystressors,andthetreatmentofdysfunctionalvoidingsyndrome. Related to her teaching endeavors, Dr Bu-chanan received the 2012 and 2015 Teaching Award for the psychology internship program at Children’s Hospital Colorado.Dr Buchanan received her bachelor’s degree in Psy-chologyfromBakerUniversity,hermaster’sdegreeinCounselingPsychologyfromtheUniversityofKansas,and her doctoral degree in Counseling Psychology fromtheUniversityofKansas.ShecompletedherpredoctoralinternshipatTempleUniversityHealthSciences Center with a focus on health psychology and her postdoctoral fellowship in pediatric psychol-ogy with a focus on pediatric transplant at the Chil-dren’s Hospital of Philadelphia. Elizabeth Calvin, MD; Author

Elizabeth Calvin, MD is a clinical assistant professor at TexasA&MCollegeofMedicineandservesasaboardcertifiedchildandadolescentpsychiatristatBluebon-net Trails Community Services in Round Rock, Texas. Dr Calvin is responsible for helping to guide the treat-mentofchildrenandadolescentsutilizingmedicationmanagement, case management services, therapy, andcommunitysupports.Sheadditionallyteacheschild and adolescent psychiatry to third and fourth yearmedicalstudentsandnursepractitionerstudentsthat rotate with her on service.Dr Calvin received her bachelor’s degree in Neurosci-encefromtheUniversityofTexasatAustinandhermedical degree from Baylor College of Medicine. She completed her adult residency and child and adoles-cent fellowship and served as a chief resident at the UniversityofColoradoSchoolofMedicine.

Contributors

85

Contributors

Lisa Costello, PhD; Author

LisaCostello,PhD,NCSPisanoutreachandadvocacycoordinatoratthePediatricMentalHealthInstituteat Children’s Hospital Colorado and a clinical assistant professorintheDivisionofChild&AdolescentPsychi-atryattheUniversityofColoradoSchoolofMedicine.DrCostelloisanationally-certifiedschoolpsychologistand a licensed clinical psychologist. Her work focuses onpromotingthesocialandemotionalwell-beingofchildren and their families in school and community settings.DrCostelloisparticularlyinterestedinpre-ventingemotionalandbehavioralchallengesinyoungchildren,promotingchildren’ssocialandemotionalcompetence,andimplementingempirically-support-edinterventionswhenchildrenpresentwithpersis-tentchallengeswithemotionregulation,socialskilldevelopment, and behavior. Dr Costello received her bachelor’s degree in Psychol-ogyfromWestVirginiaUniversityandhermaster’sdegreeinEducationalPsychology,educationalspecial-ist degree, and doctoral degree in School Psychology fromIndianaUniversity.DrCostellocompletedherpredoctoral internship at the Sarah A. Reed Children’s Centeranda2-yearpostdoctoralfellowshipinBrownUniversity’sClinicalPsychologyTrainingProgram. Scott Cypers, PhD; Author

ScottCypers,PhDisanassistantprofessorofpsychia-tryattheUniversityofColoradoSchoolofMedicineandservesasapsychologistintheF.A.M.I.L.Y.(Fo-cusedAnxietyandMoodInterventionsLeadingtoPositiveChangeInYouthandFamilies)attheHelenandArthurE.JohnsonDepressionCenter.DrCypersis responsible for providing both individual, couples, family, and group therapies focused on mood and anxiety services. Dr Cypers leads classes on anxiety treatment in adolescence in courses for psychia-try residents and previously for Children’s Hospital Colorado.Healsoregularlygiveslecturesinnationalandcommunitysettings(InternationalOCDFounda-tion,AmericanPsychologicalAssociation,schools,andcommunityorganizations)ontheidentificationandtreatment of mental health issues in adolescents, es-pecially as related to anxiety disorders and treatment. Dr Cypers’s research focuses on improving treatment outcomes around anxiety treatment as well as novel approaches to get children and adolescents to engage inexposure-basedtreatment.

Dr Cypers received his bachelor’s degree in Psychol-ogyandPhilosophyfromEmoryUniversityandhisdoctoral degree in Counseling Psychology from the UniversityofSouthernCalifornia.Hecompletedapostdoctoral fellowship in adolescent mental health attheClaremontUniversityConsortium.

Emily Edlynn, PhD; Editor, Reviewer, Author

Emily Edlynn, PhD is a pediatric psychologist for Amita Health and the Alexian Brothers Behavioral Health Hospital in Chicago, Illinois. Dr Edlynn was previously anassistantprofessorofPsychiatryattheUniversityof Colorado School of Medicine, and served as the Clinical Program Director for the Medical Day Treat-ment(MDT)programatChildren’sHospitalColorado.Dr Edlynn also has a background in pediatric pain and palliativecare,helpingtodevelopthepalliativecareserviceatChildren’sHospitalLosAngeles(CHLA).DrEdlynn has taught medical residents and psychology traineesinpalliativecare,griefandbereavement,andnon-pharmacologicalpainmanagement.DrEdlynn’sresearch has focused on program development, programevaluation,andpalliativecare.Aspartofthepalliativecareteam,DrEdlynnreceivedtheHuman-ismAwardatCHLA.Dr Edlynn received her bachelor’s degree in English from Smith College and her doctoral degree in Clinical PsychologyfromtheLoyolaUniversityofChicago.ShecompletedherinternshipatStanfordUniversityanda postdoctoral fellowship in pediatric psychology at Children’s Hospital Orange County.

Robert Freedman, MD; Reviewer

RobertFreedman,MDisanattendingphysicianatUniversityofColoradoHealth.HealsoeditstheAmericanJournalofPsychiatry.Previously,DrFreed-man was Professor and Chair of the Department of Psychiatry&BehavioralSciencesatChildren’sHospi-tal Colorado. He was also head of the Schizophrenia Center where he conducted basic and clinical research inschizophrenia.Hecontinuestotreatpatientswiththat disorder.Dr. Freedman received his medical degree from Har-vard Medical School and trained in psychiatry at the UniversityofChicago.

86

Contributors

Monique Germone, PhD; Author

MoniqueGermone,PhDisanassistantprofessorofpsychiatryattheUniversityofColoradoSchoolofMedicine and serves as a psychologist with the Pe-diatricMentalHealthInstituteatChildren’sHospitalColorado.DrGermoneprovidesoutpatientpsycho-therapy services to children and adolescents with AutismSpectrumDisorders.Shealsoprovidesinte-grated care services to children and adolescents with celiac disease. Dr Germone teaches classes for psy-chology interns and child and adolescent psychiatry residentsondiagnosisandinterventionsforchildrenandadolescentswithAutismSpectrumDisorders.Shealsoregularlylecturesincommunitysettings(schools,pediatricmedicalpractices,etc)ontheidentifica-tionandtreatmentofautismspectrumdisordersinchildren and adolescents. Her research focuses on thequalityoflifeandclinicalcareofchildrenandadolescentswithautismspectrumdisorderandceliacdisease.Dr Germone received her bachelor’s degree in Psy-chologyfromtheUniversityofHawai’iandherdoc-toral degree in Clinical Psychology from the California School of Professional Psychology. She completed her predoctoral internship at Rady Children’s Hospital in San Diego, California and her postdoctoral training at aprivatepracticeinTemecula,California. Jennifer Hagman, MD; Reviewer

JenniferHagman,MDisanassociateprofessorofpsy-chiatryattheUniversityofColoradoSchoolofMedi-cine.SheisboardcertifiedinbothChildandAdoles-cent Psychiatry and General Psychiatry. She has been theMedicalDirectoroftheEatingDisorderProgramat Children’s Hospital Colorado since 1993 and has integratedevidence-basedclinicalapproachesanda comprehensive research component into the pro-gram,whichprovidesafamily-centeredapproachtoparent-supportednutritionandrecovery.DrHagmanis a past president of the Colorado Psychiatric Society, Colorado Child and Adolescent Psychiatric Society, andEatingDisorderProfessionalsofColorado.Shesupervises psychiatry residents and gives lectures and presentationsattheUniversityofColoradoSchoolofMedicine,inthecommunity,andatnationalandinternationalmeetings.Herresearchisfocusedonfactors related to the onset, course of illness, and recovery from anorexia nervosa. She has published

manyresearcharticlesandchapters,andisanexpertinthediagnosisandtreatmentofeatingdisordersin childhood and adolescence. Dr Hagman received theDanePrughawardforDistinguishedTeachinginChild Psychiatry, the Outstanding Achievement Award from the Colorado Psychiatric Society, the Faculty Award for Mentorship for the Child and Adolescent Psychiatry Residency Class of 2013, was recognized as aWomanofDistinctionbytheMileHighGirlScoutsorganizationin2003,andwasthekeynotespeakerforthe2008NorthAmericanLeadershipConference(NALC)ofChildren’sHospitals.DrHagmanisadis-tinguishedfellowoftheAmericanAcademyofChildand Adolescent Psychiatry, the American Psychiatric Association,andtheAcademyofEatingDisorders.Dr Hagman received her bachelor’s degree in Molecu-lar,Cellular,andDevelopmentalBiology(MCDB)andPsychologyfromtheUniversityofColoradoBoulderandhermedicaldegreefromtheUniversityofKan-sas. She completed her psychiatry residency training, and child and adolescent psychiatry fellowship at the UniversityofCaliforniaIrvine.

Sharon Hunter, PhD; Author

Sharon K. Hunter, PhD is a lecturer in the Department of Psychology and Philosophy at Sam Houston State University.DrHunterteachesundergraduateandgraduate courses in physiological and developmental psychology, research methodology, and learning. She also mentors undergraduate student research proj-ectsandseniortheses.PriortoherpositionatSamHouston State, Dr Hunter was an associate professor intheDepartmentofPsychiatryattheUniversityofColorado School of Medicine, where she was a mem-ber of the Developmental Psychiatry Research Group. Herworktherefocusedontherelationshipbetweenearly brain development and later psychopathology. Dr Hunter received her bachelor’s degree from the UniversityofSouthCarolinainPsychology,hermas-ter’sdegreefromMississippiUniversityforWomeninEducation,andherdoctoraldegreefromtheUniver-sity of South Carolina in Psychology. She completed a postdoctoral fellowship with the Developmental PsychobiologyResearchGroupattheUniversityofColorado School of Medicine.

87

Contributors

Amanda Hutchison, MD; Author

Amanda K. Hutchison, MD is a child, adolescent and adultpsychiatristinprivatepracticeinDenver,Colora-do. Dr Hutchison has had an interest in child psychia-try since undergraduate and has worked on research relatedtomoodandattentiondisordersinpreschoolchildrenusingcognitiveandplaytherapy-typemeth-odologies.Shehasspecificinterestsindoingpsycho-therapy with children and adolescents. Dr Hutchison received her bachelor’s degree in Psy-chologyfromtheUniversityofColorado,BoulderandhermedicaldegreefromtheUniversityofColorado,Denver. She completed her residency in adult psychia-try and fellowship in child and adolescent psychiatry attheUniversityofColoradoDenverandChildren’sHospitalColorado.Sherecentlycompleteda2-yearprogram in psychodynamic psychotherapy through theDenverInstituteforPsychoanalysisandstarteda4-yeartrainingprogramforchildandadultpsycho-analysis in the Fall of 2016.

Laura Judd-Glossy, PhD; Author

LauraJudd-Glossy,PhDisanassistantprofessorintheDepartmentofPsychiatryattheUniversityofColo-rado School of Medicine. She serves as a pediatric psychologistontheChildPsychiatryConsultation-LiaisonServiceattheChildren’sHospitalColorado.DrJudd-Glossyprovidesconsultationandliaisonservicestopediatricpatientsandtheirfamilieswhoareadmittedforinpatientmedicalhospitalization.Sheprovides clinical supervision and training for psychol-ogy interns, psychiatry fellows, and medical students ontheConsultation-LiaisonService.DrJudd-Glossy’sresearch interests focus on how youth and families manage pediatric acute and chronic medical illness, withhermostrecentresearchbeingontheetiology,assessment,andtreatmentofnon-epilepticseizures.DrJudd-Glossyreceivedherbachelor’sdegreeinPsychology from the College of William and Mary, her master’s degree in School Counseling from Boston College, and her doctoral degree in School Psychology fromtheUniversityofTexasatAustin.DrJudd-Glossycompleted her predoctoral internship at Boston Chil-dren’s Hospital/Harvard Medical School. As a postdoc-toralfellowshipatDana-FarberCancerInstitute/HarvardMedical School, she specialized in the clinical treatment ofpediatriconcology/hematologypatientsandsurvivors.

Harpreet Kaur, PhD; Author

Harpreet Kaur, PhD is a clinical assistant professor at theUniversityofArizona,CollegeofMedicineandservesastheConsultationLiaisonPsychologistatPhoenix Children’s Hospital. Dr Kaur provides psycho-logicalservicesinaninpatientmedicalsettingtochil-dren and adolescents with chronic and acute medical conditions.Sheprovidessupervisionandtrainingtopsychologyinternsontheconsultationliaisonservice. Dr Kaur also provides lectures to advanced nursingstudentsaboutcognitivebehavioraltherapyandmindfulnessinapediatricsetting.Herresearchinterests include understanding symptom presenta-tioninethnicallydiverseyouthexposedtotraumaandexaminingtheeffectivenessofevidence-basedinterventionsinhealthcaresettings.Dr Kaur received her bachelor’s degree in Psychology andBiologyfromWhittierCollegeandherdoctoraldegreeinClinicalPsychologyfromtheUniversityofNevada,LasVegas.Shecompletedherpostdoctoralfellowship in the Medical Day Treatment program at Children’s Hospital Colorado.

88

Contributors

Sarah L. Kelly, PsyD; Author

SarahL.Kelly,PsyDisanassistantprofessorintheDepartmentsofPediatricsandPsychiatryattheUni-versity of Colorado School of Medicine. She serves as thePediatricPsychologistfortheHeartInstituteatChildren’s Hospital Colorado and provides psychologi-calassessment,intervention,andconsultationacrosstheoutpatientcardiologyclinic,subspecialtymulti-disciplinaryclinics,andinpatientcardiacintensiveand progressive care units. She is the Clinical Director oftheHeartInstituteWellnessProgram,formedtooptimizethecomprehensivepsychosocialhealthcareofchildrenwithcongenitalandacquiredheartdis-ease. Her research interests include the psychological adjustmentandhealth-relatedqualityoflifeofhigh-riskcardiacpopulations,andsheisinvolvedwiththeCardiacNeurodevelopmentalOutcomeCollaborative(CNOC)andtheNationalPediatricCardiologyQualityImprovementCollaborative(NPC-QIC).Dr Kelly received her bachelor’s degree in Psychology fromMiamiUniversityofOhioandhermaster’sanddoctoral degrees in Clinical Psychology, with a child andadolescentconcentration,fromWheatonCol-lege, Illinois. She completed her predoctoral psychol-ogy internship at Denver Health Medical Center and a pediatric psychology postdoctoral fellowship at Children’s Hospital Colorado in pediatric solid organ transplant surgery.

Jessica Malmberg, PhD; Author

JessicaMalmberg,PhDisanassistantprofessorofpsychiatryandpediatricsattheUniversityofColoradoSchool of Medicine and works as a clinical psycholo-gistinthePediatricMentalHealthInstituteandNeu-roscienceInstituteatChildren’sHospitalColorado.ShealsoservesastheClinicalDirectorofOutpatientServicesinthePediatricMentalHealthInstitute.Sheisacoursedirectorforaninterdisciplinarydidacticonpediatric behavioral medicine, supervises psychology and psychiatry trainees, and leads a training group for childrenwithdisruptivebehaviordisorders.DrMalm-bergprovidesoutpatientbehavioralhealthservicestochildren,adolescents,andfamiliespresentingwithawide spectrum of behavioral health disorders. She has strongresearchandclinicalinterestsindisruptivebe-haviordisorders,parentinginterventions,chronicpainconditions,andfunctionaldisorders.DrMalmbergis

heavilyinvolvedininnovativeprogramdevelopmentanddisseminationeffortstobringatransdiagnosticapproach to pediatric behavioral health assessment and treatment services. Dr Malmberg received her master’s degree in Psy-chology,hereducationalspecialistdegreeinSchoolPsychology, and her doctoral degree in Combined Clinical/Counseling/School Psychology, with a special-izationinclinicalchildpsychology,fromUtahStateUniversity.Shecompletedherpredoctoralinternshipat Children’s Hospital Colorado in pediatric health psychology and a postdoctoral fellowship at the Cleve-land Clinic Children’s Hospital in pediatric psychology

MaryAnn Morrow, PMHNP-BC; Author

MaryAnnMorrow,PMHNP-BCisaninstructorattheUniversityofColoradoSchoolofMedicineandisanoutpatientpsychiatricproviderwiththePediatricMentalHealthInstitute(PMHI)atChildren’sHospitalColorado.Sheisresponsiblefordiagnosticandmedi-cationmanagementforchildrenandadolescentsintheoutpatientpsychiatricclinic.Inadditiontosee-ingpatientsandtheirfamilies,shepreceptsstudentnursepractitioners.MsMorrowisinterestedinre-searchconcerningNon-SuicidalSelfInjury(NSSI)andongoinginformationconcerningdiagnosisandtreat-mentofchildrenwithAutismSpectrumDisorders.Ms Morrow received her bachelor’s degree in Nurs-ing from the Mayo Clinic in Rochester, Minnesota andhermaster’sdegreeinBusinessAdministrationfromWashingtonUniversityinStLouis,Missouri.Shestudied for both her master’s degree and the psychi-atricmentalhealthnursepractitionerdegreeattheUniversityofColorado,andisnowboardcertifiedasaPMHNP-BC.

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Contributors

Benjamin Mullin, PhD; Reviewer

Benjamin Mullin, PhD is an assistant professor of psy-chiatryattheUniversityofColoradoSchoolofMedi-cine and a psychologist in the Pediatric Mental Health Institute’soutpatientclinicatChildren’sHospitalColo-rado.DrMullinprovidesshort-term,evidence-basedindividual and group therapy to youths with acute and disabling anxiety. Dr Mullin also provides training for clinical psychology externs, interns, and psychiatry residentsonevidence-basedtreatmentsforanxiety,tics,andsleepdisorders.DrMullin’sresearchfocuseson the pathophysiology of anxiety disorders among youth,andinparticular,howsleepdisruptionmayprecipitateemotiondysregulationbyalteringactivityin key neural circuits. Dr Mullin received his bachelor’s degree in Psychology fromClarkUniversityandhismaster’sanddoctoraldegreesinClinicalPsychologyfromtheUniversityofCalifornia,Berkeley.Hecompleteda2-yearresearchfellowshipinsleepmedicineandtranslationalneu-roscienceattheUniversityofPittsburghSchoolofMedicineanda1-yearfellowshipinpediatricanxietydisorders at Children’s Hospital Colorado.

Douglas K. Novins, MD; Reviewer, Editor-in-Chief

DouglasK.Novins,MDistheCannonY.&LydiaHar-vey Chair in Child and Adolescent Psychiatry, and ChairoftheDepartmentofPsychiatry&BehavioralSciences at Children’s Hospital Colorado. He is also professorofpsychiatryandcommunity&behavioralhealthattheUniversityofColoradoAnschutzMedicalCampus. Dr Novins serves as the leader of child and adolescent behavioral health at Children’s Hospital ColoradoandtheUniversityofColoradoAnschutzMedical Campus, leading the ongoing development of a diverse set of clinical, training, and research pro-gramswithover60facultyand275staff.DrNovins’expertiseisintheareasofadolescentsubstance-relatedproblemsandtraumaticexperiences,par-ticularlyamongAmericanIndianandAlaskaNativeyouth. He is also Deputy Editor of the Journal of the American Academy of Child & Adolescent Psychiatry (JAACAP),thehighestrankedpublicationinchildandadolescent psychiatry and developmental psychology. Hewasrecentlyselectedtobethe7thEditor-in-ChiefofJAACAPwiththefirstissueofhistermscheduledto

bepublishedinJanuary,2018.Dr Novins received his bachelor’s degree in History and Premedical Studies from Columbia College and hismedicaldegreefromColumbiaUniversity’sCollegeof Physicians and Surgeons. He trained in general psy-chiatryatNewYorkUniversity/BellevueHospitalandinchildandadolescentpsychiatryattheUniversityofColorado.TheNationalInstituteofMentalHealthsupportedDrNovins’researchtrainingattheUni-versity of Colorado through a postdoctoral research fellowship in developmental psychobiology and a career development award in mental health services research.

Philip C. O’Donnell, PhD; Reviewer

Philip C. O’Donnell, PhD is an assistant professor in the Department of Psychiatry and Behavioral Sciences atNorthwesternUniversityandtheDirectoroftheCookCountyJuvenileCourtClinic.PriortojoiningNorthwestern’s faculty, Dr O’Donnell was an assistant professorofpsychiatryattheUniversityofColoradoSchool of Medicine and the Clinical Director of the Intensive Psychiatric Services program at Children’s Hospital Colorado. Dr O’Donnell has specialized train-ing in the forensic assessment of children and families and has served as an expert witness and consultant to judges,attorneys,caseworkers,andprobationofficersin California, Colorado, and Illinois. Dr O’Donnell received his bachelor’s degree in Psy-chologyfromCreightonUniversity,andhisdoctoraldegreeinClinicalPsychologyfromLoyolaUniversityChicago.Healsoholdsamaster’sdegreeinJurispru-dence,ChildandFamilyLaw,fromLoyolaUniversityChicago’sSchoolofLaw.HecompletedapostdoctoralfellowshipinforensicpsychologyattheUniversityofSouthernCalifornia’sInstituteofPsychiatry,Law,andBehavioral Sciences.

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Contributors

Lina Patel, PsyD; Author

LinaPatel,PsyDisanassistantprofessorofchildandadolescentpsychiatryattheUniversityofColoradoSchoolofMedicine,practicingatChildren’sHospitalColorado. Dr Patel is the Director of Psychology for theAnnaandJohnJ.SieCenterforDownSyndrome,amultidisciplinaryconsultativecliniccoordinatingcare for infants, children, teens, and young adults with Down syndrome. Dr Patel is responsible for the management of all referrals for psychological treat-mentandevaluation.Sheprovidesconsultationwithschools, parent training regarding the management of challengingorunsafebehaviors,evaluationfordualdiagnoses(DownsyndromeandAutism),toilettrain-ing,anddesensitizationtomedicaldevices(suchashearingaidsandCPAP)andprocedure-relateddis-tress. Outside of her clinical work, she has presented tonumerousorganizationsacrossthecountrywithafocusonbehavioralinterventionswithindividualswith Down syndrome. She also conducts research on clinicalissuesimpactingthosewithDownsyndrome.Dr Patel received her bachelor’s degree in Psychology fromtheUniversityofOklahomaandhermaster’sand doctoral degrees in Clinical Psychology from the UniversityofDenver’sGraduateSchoolofProfession-al Psychology. She completed her internship training atBostonUniversityMedicalCenterandherpostdoc-toralfellowshipatStanfordUniversity’sLucilePackardChildren’s Hospital.

Randal Ross, MD; Author

Randal Ross, MD, who passed away as this issue of theJournalwascomingtopress,wastheL.McCarty-Fairchild Professor of Child Psychiatry in the depart-ments of Psychiatry and Pediatrics and the Director of theSchizophreniaResearchCenterattheUniversityof Colorado School of Medicine. Dr Ross served the UniversityofColoradoSchoolofMedicinefor24years and directed research training programs for undergraduates, medical students, general psychiatry residents, child and adolescent psychiatry residents, and postdoctoral trainees. His research focused on understanding the developmental pathway to psychi-atric illnesses, including schizophrenia and ADHD, and developmentandtestingofnovelprimarypreventionstrategies.

Dr Ross received his bachelor’s degree in Physiologi-calPsychologyfromtheUniversityofCalifornia,SantaBarbaraandhismedicaldegreefromYaleUniversity.He completed both general and child and adolescent psychiatryresidenciesattheUniversityofWashing-toninSeattle,Washington.DrRossreceivedresearchpostdoctoral training from the Developmental Psycho-biologyResearchGroupattheUniversityofColoradoSchool of Medicine.

Elise M. Sannar, MD; Author

Elise M. Sannar, MD is an assistant professor of psychiatryattheUniversityofColoradoSchoolofMedicine,practicingatChildren’sHospitalColorado.DrSannarisoneof2attendingpsychiatristsontheNeuropsychiatricSpecialCareUnit(NSC),anintensiveinpatientanddaytreatmentprogramforchildrenandadolescents with comorbid psychiatric and develop-mentalissues.Sheisinvolvedinmultiplesubspecialtyclinics in the hospital, including the Prader Willi Mul-tidisciplinaryClinic,the22q11.2DeletionSyndromeClinic, and the Sie Center for Down Syndrome. She hasalsoparticipatedinnationalresearchstudieslook-ingattheeffectsofnovelagentsonthecorebehav-ioralphenotypeofFragileXSyndrome.Inadditiontomanaginghersubspecialtyclinicpatients,DrSannarseesotheroutpatientsforongoingmedicationman-agement. Dr Sannar brings her passion for serving specialneedspatientstoherteachingoffellowsandresidents. She provides direct supervision to residents rotatingthroughtheNSCunitandlecturestogeneralpsychiatry residents, child and adolescent psychiatry fellows, and developmental pediatrics fellows.Dr Sannar received her bachelor’s degree in Women’s Studies and Chemistry from Pomona College and her medicaldegreeattheUniversityofChicago.Shecom-pleted her residency and fellowship trainings at the UniversityofColoradoSchoolofMedicine.

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Contributors

Marissa Schiel, MD, PhD; Editor, Reviewer, Author

Marissa Schiel, MD, PhD is an assistant professor of psychiatryattheUniversityofColoradoSchoolofMedicine.DrSchielisanattendingpsychiatristfortheEatingDisorderProgramatChildren’sHospitalColora-do. She also serves as the Medical Director of the Out-patientPsychiatryClinicinthePediatricMentalHealthInstitute.Aspartofheroutpatientclinicalresponsibili-ties,shecollaborateswithMedicalDayTreatmenttoprovidepsychiatriccareforpatientsenrolledintheirprogram.DrSchielisactivelyinvolvedinteachingandcommitteemembershipforthechildpsychiatryresi-dency program. Dr Schiel received her bachelor’s degrees in Biochem-istryandHonorsBiologyfromtheUniversityofIllinois,Urbana-ChampaignandherdoctoraldegreeinBio-chemistryandmedicaldegreefromIndianaUniversity.Dr Schiel completed her general psychiatry residency andherchildpsychiatryfellowshipattheUniversityofColorado and served as a chief resident

Elizabeth Steinberg, PhD; Author

Elizabeth Steinberg, PhD is an assistant professor in theDepartmentofPsychiatryattheUniversityofColorado School of Medicine. She is a pediatric psy-chologist for the Solid Organ Transplant program at Children’s Hospital Colorado. Dr Steinberg conducts pre-transplantevaluations,consultations,andinter-ventionsforheart,liver,andkidneypediatricpatientsand families. Her research focuses on adherence inter-ventions,assessmentofadherence,andpsychosocialaspectsthatimpactcopingwithorgantransplantation.Dr Steinberg received her bachelor’s degree in Psy-chologyfromYaleUniversity,hermaster’sdegreeinClinicalPsychologyfromTempleUniversity,andherdoctoral degree in Clinical Psychology, with an empha-sis on Developmental Psychopathology, from Temple University.Shecompletedherpredoctoralinternshipin pediatric health psychology at Children’s Hospital Colorado and her postdoctoral fellowship in pediatric psychology with an emphasis on pediatric solid organ transplant at Children’s Hospital Colorado.

Ayelet Talmi, PhD; Reviewer

Ayelet Talmi, PhD is an associate professor of psychia-tryandpediatricsattheUniversityofColoradoSchoolof Medicine and a pediatric psychologist at Children’s Hospital Colorado. Dr Talmi is the Director of Integrat-ed Behavioral Health at the Pediatric Mental Health InstituteandservesastheProgramDirectorofProjectCLIMB,anintegratedmentalhealthandbehavioralservicesprograminahigh-volumepediatricresidencytrainingclinic.DrTalmi’spositionsincludeservingasthe Associate Director of the Irving Harris Program in ChildDevelopmentandInfantMentalHealth(afel-lowship training program in early childhood mental health),theProjectLeadoftheFirst1,000DaysInitia-tiveatChildren’sHospitalColorado,andtheAssociateDirectoroftheCenterforFamilyandInfantInteraction(atransdisciplinarytrainingcenterforprofessionalsworkingwithfragileinfantsandtheirfamilies).Herprimary clinical and research interests focus on build-ing sustainable service delivery systems for children andfamilies,integratingbehavioralhealthservicesintoprimarycaresettings,andsupportingyoungchildren with special health care needs and their families. Dr Talmi engages in workforce capacity build-ing, training, technical assistance, and professional developmenteffortsandhastrainedthousandsofhealth,mentalhealth,alliedhealth,andcommunity-basedprofessionals.DrTalmiisactivelyengagedinpolicyeffortsaroundbehavioralhealthintegrationinprimarycaresettings,practicetransformation,andpayment reform. She is also involved in early child-hoodsystemsbuildingefforts,advocacy,andpolicyinColoradoandnationally.DrTalmiisaGraduateZeroToThreeLeadersforthe21stCenturySolnitFellowandaPastPresidentoftheColoradoAssociationforInfantMental Health.Dr Talmi received her bachelor’s degree in Psychology fromBinghamtonUniversityandherdoctoraldegreein Child Clinical and Developmental Psychology from theUniversityofDenver.Shecompletedherintern-ship at Children’s Hospital Colorado and her postdoc-toral fellowship in neurobehavioral development with the Developmental Psychobiology Research Group (DPRG)attheUniversityofColoradoSchoolofMedi-cine, Department of Psychiatry.

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Contributors

Eileen Twohy, PhD; Author

Eileen Twohy, PhD is an assistant professor of psychia-tryattheUniversityofColoradoSchoolofMedicineand works as a pediatric psychologist at the Pediatric MentalHealthInstitute(PMHI)ofChildren’sHospitalColorado.DrTwohydivideshertimeacrossthecon-sultation/liaisonservice,intensivepsychiatricservices,andtheoutpatientclinicatPMHI.Sheenjoysprovid-ingconsultationtomedicalteamsaswellasindividualand group therapy to children, adolescents, and familiespresentingwithabroadrangeofbehavioralhealth concerns. Dr Twohy’s role includes supervision and training of psychology interns and externs, medi-cal students, and psychiatry fellows. Her interests include interdisciplinary treatment for children and adolescents with comorbid psychiatric and medical diagnoses,trauma-informedtreatment,behavioralhealthcareaccessforunderservedpopulations,andtransdiagnosticapproachestobehavioralhealth.Dr Twohy received her bachelor’s degree in English from Grinnell College and her doctoral degree in ClinicalPsychologyfromCatholicUniversityinWash-ington, DC. She completed a predoctoral internship inpediatricpsychologyatChildren’sHospitalLosAngeles/UniversityofSouthernCalifornia,UniversityCenterforExcellenceinDevelopmentalDisabilities(UCEDD)andapostdoctoralfellowshipinoutpatientpsychology at Children’s Hospital Colorado. Peng-Peng Wei, MD; Author

Peng-PengWei,MDisaresidentphysicianinemer-gencymedicineatNewYork-PresbyterianUniversityHospital of Columbia and Cornell. Dr Wei completed theworkreflectedinthepaperpublishedinthisissueof the Colorado Journal of Psychiatry and Psychology asamedicalstudentwhilepartoftheUniversityofColorado School of Medicine Research Track.Dr Wei received her bachelor’s degree in Molecular andCellBiologyandPsychologyfromtheUniversityof California, Berkeley and her medical degree from theUniversityofColorado.

Jason Williams, PsyD, MSEd; Author

JasonWilliams,PsyD,MSEdisanassociateprofessorofpsychiatryattheUniversityofColoradoSchoolofMedicine and serves as Clinical Director and Direc-torQualityandSafetyinthePediatricMentalHealthInstituteattheChildren’sHospitalColorado.DrWil-liamshasaninterestinthedevelopmentofinnovativeteachingmethodologiesininter-professionalteams.Clinically, his interests lie in the use of technology both for clinical outcomes and in the development of transdiagnosticservicedelivery.Heenjoysworkingwith children and families clinically where he focuses on people with impulse control disorders.Dr Williams is the past president of the Colorado PsychologicalAssociationandthepastChairoftheAssociationofPredoctoralandPostdoctoralIntern-shipCenters(APPIC);heiscurrentlytheChairoftheCouncilofChairsofTrainingCouncils(CCTC).Dr Williams received his master’s degree in Educa-tionfromtheUniversityofSouthernCaliforniaandhis doctoral degree from the California School of ProfessionalPsychologyinLosAngeles,California.He completed an internship and postdoctoral train-ingprogramattheChildren’sHospitalinLosAngeles,where he worked for 12 years prior to returning home to Colorado.

Acknowledgements

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Acknowledgements

Acknowledgements

Peerreviewisthemajormethodforassuringhigh-qualityscholarshipinacademicmedicine.Aknowledgeableandthoughtfulpeerreviewmakesthepapersshereviewsbetter.Weacknowledgetheimportantcontributionsof our colleagues who served as peer reviewers for this issue of the Colorado Journal of Psychiatry and Psychology.

• Emily Edlynn

• Robert Freedman

• JenniferHagman

• Benjamin Mullin

• Doug Novins

• Philip O’Donnell

• Marissa Schiel

• Ayelet Talmi

Dedication

This issue is dedicated to the memory of Professor Randy Ross, who passed away as this issue was coming topress.RandywasanintellectualleaderofourextensivedevelopmentalresearchportfolioattheUni-versityofColoradoandahighlyrespectedscientist.Randy’sworkintranslationalneuroscienceandhisex-tensiveknowledgeofchilddevelopmenthasledtoinnovativeapproachestopreventingthedevelopmentof severe mental illness. He came to Colorado to train in our postdoctoral fellowship in developmental psychobiology,aprogramthatheeventuallywouldleaduntilhisdeath.Ahighlysoughtafterteacherandmentor,Randywasparticularlytalentedathelpingallofustoseeourworkfromdifferentperspectives,enablingustodomorerigorousandinformativeresearch.AsChairoftheDepartmentofPsychiatry’sPro-motionsCommittee,RandyimmediatelysawthevalueofthisJournal for advancing the scholarship of our faculty. Indeed, Randy served as senior author for 2 papers in this issue of the Journal, underscoring his scientificaccomplishments,mentorship,anddedicationtoourfacultyandtrainees.Wetreasurehislegacyeven as we struggle with coming to terms with our loss.

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13001 E 17th Pl, MS-F546 | Bldg 500, Rm E2322 | Aurora, CO 80045

Department of Psychiatry | School of Medicine | University of Colorado

About the University of Colorado School of Medicine Department of Psychiatry

TheUniversityofColoradoSchoolofMedicineisrankedinthetop10byU.S.News&WorldReportinmultiplemedicalspecial-ties.LocatedontheAnschutzMedicalCampusinAurora,Colorado,theSchoolofMedicinesharesitscampuswithChildren’sHospitalColoradoandUniversityofColoradoHealth.TheDepartmentofPsychiatryprovidesclinicalservicesthroughtheAddictionTreatmentServices,Children’sHospitalColorado,UniversityofColoradoHospital,andinconjunctionwithDenverHealthMedicalCenterandtheDenverVeteransAdministrationHospital.TheDepartmentofPsychiatrytrainingprogramsencompassafullspectrumofeducationallevels(frommedicalstudentandresidencyeducationthroughpostdoctoralfellow-ships)andmentalhealthdisciplines(eg,psychology,psychiatry,socialwork,andnursing),andarewidelyrecognizedfortheirconsistenthighquality.

Withover167full-timeand366volunteerfacultymembers,theDepartmentofPsychiatryisoneofthelargestintheUnitedStates. Its residency program also ranks among the largest programs, with 45 residents and over a dozen fellows. Many of our facultyhavepositionsofleadershipinnationalorganizations,includingtheAmericanPsychiatricAssociation,theAmericanPsychologicalAssociation,andtheAmericanAcademyofChildandAdolescentPsychiatry.

Intermsofresearch,theDepartmentofPsychiatryregularlyranksasoneofthetop3ontheUniversityofColoradoAnschutzMedicalCampus,andwasrecentlyranked13thinthenationforresearchfunding.ItisalsooneofthestrongestcentersintheVeteran’sAdministrationforfundinginmentalhealthresearch.Thebreadthanddepthofscientificaccomplishmentsspantheneurosciences,developmentalneurobiology,addictions,infantdevelopment,childandadolescentpsychiatry,behavioralim-munology, schizophrenia, depression, transcultural, and public psychiatry.

Recentresearchawards,investmentsinclinicalservices,andteachingbybothouraffiliatedinstitutionsandthephilanthropiccommunityhavestrengthenedandenlargedourexistingprogramsaswecontinueourcommitmenttoabiopsychosocialmodel,medicalandpsychiatriceducation,aninterdisciplinaryresearchapproach,andtheprovisionofclinicalservices.

About the Division of Child and Adolescent Psychiatry Asoneoftheoldestandmost-respectedacademicprogramsinchildren’smentalhealthinthenation,theDivisionofChildandAdolescentPsychiatrysupportsawiderangeofclinical,teaching,andresearchprograms.TheDivisionisparticularlywell-knownforadvancingthescienceandpracticeofchildren’smentalhealthintheareasofaddictions,anxiety,autismspectrumdisorders,underservedpopulations,eatingdisorders,integratedcare,psychosisandearly-onsetschizophrenia,psychosomaticmedicine, stress and trauma, and telemental health.

TheDivisionofChildandAdolescentPsychiatrycombinedeffortswithChildren’sHospitalColoradoin2002todevelopwhatisnowthePediatricMentalHealthInstitute.Children’sHospitalColoradosees,treats,andhealsmorechildrenthananyotherhospital in the region, providing integrated pediatric health care services at the Anschutz Medical Campus as well as 16 other locationsalongColorado’sFrontRange.Thehospitalisnationallyrankedasaleaderinpediatriccare,consistentlyrecognizedbyU.S.News&WorldReportasoneofthetop10children’shospitalsinthenation.

ThePediatricMentalHealthInstituteprovidesacompletecontinuumofpsychiatricservices,includingoutpatient,emergency,partialhospitalization,andinpatientserviceswithanemphasisondevelopingcoordinatedsystemswithinthehospitalaswellascollaboratingwithotheragenciesandproviders.Ourinterdisciplinaryfacultyandstaffincludespsychiatrists,psychologists,socialworkers,andnurses.Theinstituteisinthemidstofamajorexpansionthatistouchingalllevelsofclinicalcare,teaching,research,andscholarship,assuringitscontinuedplaceasoneofthenation’sleadingcentersforchildren’smentalhealth.

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