Moving Target: The Moving Target: The Developing Social Developing Social Brain & Brain & Psychopathology Psychopathology Research Committee Research Committee Group for the Advancement of Psychiatry (GAP) Group for the Advancement of Psychiatry (GAP) Jacob Kerbeshian Jacob Kerbeshian Co-author: Larry Burd Co-author: Larry Burd Other committee members: Russell Gardner, Beverly Sutton, Other committee members: Russell Gardner, Beverly Sutton, John Beahrs, John Beahrs, Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Schwartz, Morton Sosland, Carlo Carandang, Doug Kramer, Schwartz, Morton Sosland, Carlo Carandang, Doug Kramer, John Looney John Looney
Transcript
Moving Target: The Moving Target: The Developing Social Brain & Developing Social Brain &
Group for the Advancement of Psychiatry (GAP)Group for the Advancement of Psychiatry (GAP)
Jacob KerbeshianJacob KerbeshianCo-author: Larry BurdCo-author: Larry Burd
Other committee members: Russell Gardner, Beverly Sutton, John Beahrs, Other committee members: Russell Gardner, Beverly Sutton, John Beahrs, Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Schwartz, Morton Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Schwartz, Morton
Sosland, Carlo Carandang, Doug Kramer, John LooneySosland, Carlo Carandang, Doug Kramer, John Looney
Jacob Kerbeshian and Larry Burd, Moving Jacob Kerbeshian and Larry Burd, Moving Target: The Developing Social Brain and Target: The Developing Social Brain and
(research (research ≈≈ blind men & elephant) blind men & elephant)Theory requisite for proper studyTheory requisite for proper study
Psychodynamics appropriately no longer Psychodynamics appropriately no longer guides psychiatry nowguides psychiatry now
But therefore few bridges between domain of But therefore few bridges between domain of personal knowledge & neurobiology datapersonal knowledge & neurobiology data
Requirements of overarching Requirements of overarching theorytheory
Comprehensible to the psychiatristComprehensible to the psychiatrist Intuitively acceptable to the publicIntuitively acceptable to the publicScientifically soundScientifically soundCan overcome the crude reductionism of Can overcome the crude reductionism of
“biochemical imbalance”“biochemical imbalance”
DSM III & precursorsDSM III & precursors
Menu-like seeming specificityMenu-like seeming specificity Earlier editions used narrative Earlier editions used narrative
Like introductions of present editionsLike introductions of present editions
Documents ok but these presently used more Documents ok but these presently used more specifically than intended specifically than intended Disorders not valid clinical diagnoses nor illnessesDisorders not valid clinical diagnoses nor illnesses Rather spectra from symptom complex to diseaseRather spectra from symptom complex to disease Considered categories even when clearly dimensionalConsidered categories even when clearly dimensional
““Co-morbidities”Co-morbidities”
Term used because manual omits Term used because manual omits dimensionsdimensions
Original intent of DSM-III Original intent of DSM-III Focused on clinical decision-making Focused on clinical decision-making Not on defining “caseness”Not on defining “caseness”
Impairment & need for treatment not Impairment & need for treatment not indicated in dx categoriesindicated in dx categories
Requirements for diagnostic validityRequirements for diagnostic validity
Differentiation of pathology from normalityDifferentiation of pathology from normalityPathological states represent statistical Pathological states represent statistical
variations from physiological normsvariations from physiological normsPathognomic symptom expressionPathognomic symptom expressionSyndromal patternsSyndromal patterns
Design & Use of DSMDesign & Use of DSM
Designed for diagnostic gatekeeper Designed for diagnostic gatekeeper purposes or screeningpurposes or screening
But present use involves rigid criteria for But present use involves rigid criteria for diagnosis (not just diagnostic screening)diagnosis (not just diagnostic screening)
Stems from lack of an integrating and Stems from lack of an integrating and organizing basic science for the specialtyorganizing basic science for the specialty
Biopsychosocial ModelBiopsychosocial Model
Engel’s model utilized 3 levels of Engel’s model utilized 3 levels of organizationorganization
Reason: dualism had caused major flaws Reason: dualism had caused major flaws in biomedical sciencein biomedical science
BPS model fostered intrasystemic BPS model fostered intrasystemic examination & cross-systemic transactionsexamination & cross-systemic transactions
Reciprocal & interactive causality more Reciprocal & interactive causality more accurate than linear casuality (implied by accurate than linear casuality (implied by bio- level employed in isolation)bio- level employed in isolation)
Attraction & integration of psychodynamics missedAttraction & integration of psychodynamics missed Humanistic & more interesting emotionallyHumanistic & more interesting emotionally Compelling & intellectually stimulatingCompelling & intellectually stimulating Incorporated developmental frameworkIncorporated developmental framework Bridged normality & psychopathologyBridged normality & psychopathology Internally consistent, self-contained featuresInternally consistent, self-contained features Metaphors of “biological” psychiatry reductionistic Metaphors of “biological” psychiatry reductionistic
Psychodynamics failed from lack of data-supportPsychodynamics failed from lack of data-support But nothing replaced itBut nothing replaced it
Social Brain ModelSocial Brain Model
Sits on the 4-legs of neurobiological research, Sits on the 4-legs of neurobiological research, DSM, BPS model & developmental approachDSM, BPS model & developmental approach Each gives it utility and efficacy Each gives it utility and efficacy But neither singly nor in combination do they fulfill the But neither singly nor in combination do they fulfill the
function of an integrating organizing frameworkfunction of an integrating organizing framework Must avoid traps of self-fulfilling theory-building Must avoid traps of self-fulfilling theory-building
without empiric testabilitywithout empiric testability Must allow easy movement amongst levelsMust allow easy movement amongst levels Practitioners and patients must comprehend & Practitioners and patients must comprehend &
acceptaccept
Additional requirementsAdditional requirementsPossess humanistic valuePossess humanistic valueFoster researchFoster researchShow clinical practicabilityShow clinical practicabilityDemonstrate compatibility with nosologyDemonstrate compatibility with nosologyDefine caseness in psychopathologyDefine caseness in psychopathologyPosition theory in biology applied to medicinePosition theory in biology applied to medicineFound compelling –stimulate intellectuallyFound compelling –stimulate intellectually Incorporate developmental frameworkIncorporate developmental frameworkBridge normality & psychopathologyBridge normality & psychopathology
Defined: Social brain =Defined: Social brain =
Summed synergy of brain circuits subserving Summed synergy of brain circuits subserving social functionsocial function Emphasis on brain of the human having evolved with Emphasis on brain of the human having evolved with
environment characteristics reflected in brain environment characteristics reflected in brain Each brain having developed uniquelyEach brain having developed uniquely
Major brain function: conspecific communicationMajor brain function: conspecific communication Note similarities & contrasts on multiple brain levels Note similarities & contrasts on multiple brain levels Brings ethology & evolutionary science to specialtyBrings ethology & evolutionary science to specialty
Evolutionary science applied to Evolutionary science applied to psychiatrypsychiatry
Allows explanation of gender differencesAllows explanation of gender differences Conceives mind as collection of subsystems that Conceives mind as collection of subsystems that
have responded to natural selection have responded to natural selection mechanisms that solve particular problem setsmechanisms that solve particular problem sets
Provides insights about violenceProvides insights about violence Suggests hypotheses about particular disordersSuggests hypotheses about particular disorders
eg, ADHD as hunter-adaptation (at the expense of eg, ADHD as hunter-adaptation (at the expense of school-adaptation)school-adaptation)
eg, Mania is a communicational state (misdirected eg, Mania is a communicational state (misdirected alpha behaviors)alpha behaviors)
Waddington concept (from Embryology)Waddington concept (from Embryology) ““Variation in resistance to change from genetic Variation in resistance to change from genetic
or environmental influences on the part of or environmental influences on the part of inherited traits” inherited traits” Ditch analogy: on a newly graded road, earlier Ditch analogy: on a newly graded road, earlier
grooves predict later deeper ones after more raingrooves predict later deeper ones after more rain Inherited number of limbs resist change more than Inherited number of limbs resist change more than
extremity adaptations for locomotion & other functionsextremity adaptations for locomotion & other functions
Relevance to development issuesRelevance to development issues Predictable developmental course, neuron-Predictable developmental course, neuron-
determined behaviors more active with repetitiondetermined behaviors more active with repetition
Case of NN – overviewCase of NN – overview
Male followed from age 6 to 25 yearsMale followed from age 6 to 25 yearsPresented range of DSM comorbiditiesPresented range of DSM comorbidities
Chief Complaint at age 6: Chief Complaint at age 6: Oppositional behavior, temper outbursts Oppositional behavior, temper outbursts OCDOCD
Birth-Perinatal historyBirth-Perinatal history
Premature Premature Survived 2 cardiac arrests as neonateSurvived 2 cardiac arrests as neonate In foster home for first 3 months – ?In foster home for first 3 months – ?
neglectneglectDevelopmental milestones left unrecordedDevelopmental milestones left unrecordedNatural mother displayed inadequate Natural mother displayed inadequate
nurturing skills so adopted away at age 18 nurturing skills so adopted away at age 18 monthsmonths
Birth ParentsBirth Parents
Birth mother Birth mother 19 years old at his birth, 19 years old at his birth, Hearing impairment ?from congenital rubella Hearing impairment ?from congenital rubella Alcohol dependentAlcohol dependent
Birth father: Birth father: 25 years old at his birth 25 years old at his birth Abandoned mo & child when learned of Abandoned mo & child when learned of
pregnancypregnancyUnknown family hxUnknown family hx
Adoptive parents & early lifeAdoptive parents & early life
Mother health care worker; Father professionalMother health care worker; Father professional They noted after adoption: They noted after adoption:
Social isolation, verbal non-responsivity, gaze Social isolation, verbal non-responsivity, gaze avoidance, lengthy episodes of repetitive rocking avoidance, lengthy episodes of repetitive rocking behaviorbehavior
Walked clumsily – some toe-walkingWalked clumsily – some toe-walking Banged head in crib; seemed accident-proneBanged head in crib; seemed accident-prone Temper tantrums Temper tantrums Disturbed routines; play featured ritualistic featuresDisturbed routines; play featured ritualistic features
Ages 2-4 yearsAges 2-4 years
At age 2 minimal language mostly At age 2 minimal language mostly uncommunicativeuncommunicative
Then age 2, lower extremity fracture with cast:Then age 2, lower extremity fracture with cast: Mother & grandfather spent much time reading to himMother & grandfather spent much time reading to him Remained emotionally distant but no echolalia nor Remained emotionally distant but no echolalia nor
pronomial reversalspronomial reversals
At age 35 months, developed 3-word phrasesAt age 35 months, developed 3-word phrases At age 4 years, toilet training occurredAt age 4 years, toilet training occurred
Developmental gainsDevelopmental gains
Between 4 & 6 years, remission of some Between 4 & 6 years, remission of some prior problems prior problems Reduced pre-sleep rocking, night terrors, & Reduced pre-sleep rocking, night terrors, &
Remained withdrawn & showed little initiative Remained withdrawn & showed little initiative Word-finding difficulties remained in evidenceWord-finding difficulties remained in evidence
Age 6 yearsAge 6 years
Seen for first time by JKSeen for first time by JKMany unverifiable tall talesMany unverifiable tall tales Identification with Darth VaderIdentification with Darth VaderCompulsively arranged things in roomCompulsively arranged things in roomExamination: large girth & general statureExamination: large girth & general stature
Clumsy, disjointed, dyspraxicClumsy, disjointed, dyspraxicGood eye contact with smilingGood eye contact with smilingArticulation problem; Vocabulary okArticulation problem; Vocabulary okExpressed tantruming & annoyanceExpressed tantruming & annoyancePreoccupied with specific rulesPreoccupied with specific rules
Diagnoses age 6Diagnoses age 6
History of autistic disorderHistory of autistic disorder Alternative diagnosis: OCD with residual sx of autismAlternative diagnosis: OCD with residual sx of autism
Oppositional defiant disorderOppositional defiant disorder Mood disorder NOS, manifested through temper Mood disorder NOS, manifested through temper
outbursts, periods of withdrawal, sleep outbursts, periods of withdrawal, sleep disturbance, excessive involvement in fantasy disturbance, excessive involvement in fantasy The last could also have stemmed from autistic The last could also have stemmed from autistic
66thth grader graderHad made significant developmental gainsHad made significant developmental gainsGrades of B and C; Tae Kwan Do lessonsGrades of B and C; Tae Kwan Do lessonsSome regression at 9 when sister bornSome regression at 9 when sister born
Pattern of impulsive aggressiveness with Pattern of impulsive aggressiveness with dramatic gestures/threatsdramatic gestures/threats
Rich fantasy life – Rambo featuredRich fantasy life – Rambo featuredActed out in playActed out in play
Symptoms Age 11 yearsSymptoms Age 11 years
Need for environmental order, mannerismsNeed for environmental order, mannerisms Since age 8, had motor & vocal ticsSince age 8, had motor & vocal tics Perseverated when stressed Perseverated when stressed
Would echo movie dialogWould echo movie dialog
Restless sleep, early awakening with rockingRestless sleep, early awakening with rocking Mood changesMood changes Moderately obeseModerately obese Hand sniffingHand sniffing
Age 11 dx & txAge 11 dx & tx Tx for attentional and affective symptomsTx for attentional and affective symptoms Desipramine then protyptaline with Desipramine then protyptaline with
psychotherapypsychotherapy Became manic secondary to the TCABecame manic secondary to the TCA Dx: Bipolar I ?amplified by TCADx: Bipolar I ?amplified by TCA OCDOCD History of autistic disorderHistory of autistic disorder Aggressive to family dog & sisterAggressive to family dog & sister Li stabilized mood and he slept betterLi stabilized mood and he slept better Teased sister but not aggressive to herTeased sister but not aggressive to her
Ages 13-15Ages 13-15
Li discontinued secondary to diabetes Li discontinued secondary to diabetes insipidusinsipidus
Clonazepam targeted mood & tic disorderClonazepam targeted mood & tic disorderLi retried along with diuretic plus Li retried along with diuretic plus
clonazepam clonazepam tolerable polyurea with sx tolerable polyurea with sx reductionreduction
IQ = 106; projective testing suggested IQ = 106; projective testing suggested bipolar disorderbipolar disorder
Grades: Bs, Cs, DsGrades: Bs, Cs, Ds
Hospitalizations at ages 15 & 16Hospitalizations at ages 15 & 16
He picked a fight at school while exaggeratedly He picked a fight at school while exaggeratedly laughing & insulting others, thenlaughing & insulting others, then Took knife to schoolTook knife to school Proclaimed he was ninja Proclaimed he was ninja Suggested he’d torch sister’s roomSuggested he’d torch sister’s room Banged on walls at homeBanged on walls at home
Age 16: increasing irritability, grandiosity, threats Age 16: increasing irritability, grandiosity, threats & injured sister though tics now minimal; Li and & injured sister though tics now minimal; Li and clonazepam discontinued; carbamazepine usedclonazepam discontinued; carbamazepine used
Status at 17Status at 17Active interest in girlsActive interest in girls
Tried to impress them with grandiosity as Tried to impress them with grandiosity as wrestlerwrestler
Individualized education plan to deal with Individualized education plan to deal with “serious emotional disturbance”“serious emotional disturbance”
More purposefully negative to parentsMore purposefully negative to parentsThreatened them with child protective Threatened them with child protective
servicesservices
Divalproex EffectDivalproex Effect
Used after d/cing clonazepam & CPZUsed after d/cing clonazepam & CPZReduced sx: No racing thoughts, more Reduced sx: No racing thoughts, more
calmness, better sleep, better response to calmness, better sleep, better response to curfews, preoccupied with Mafia gangster in curfews, preoccupied with Mafia gangster in more appropriate joking manner, compliant more appropriate joking manner, compliant with medicationwith medication
Increased adaptation: Kept up with Increased adaptation: Kept up with schoolwork, moved to nearby community for schoolwork, moved to nearby community for technical training, had own car, managed own technical training, had own car, managed own funds (from social security)funds (from social security)
Age 19Age 19
At 19 d/ced divalproex, feeling no needAt 19 d/ced divalproex, feeling no needLeft technical schoolLeft technical schoolBriefly engaged to 16 y.o. girlBriefly engaged to 16 y.o. girlOccasional brief episodes of depressionOccasional brief episodes of depressionFragile X examined for; negativeFragile X examined for; negative
At age 20At age 20
Panic attacks beganPanic attacks beganFrequent ER visits with brief overnight staysFrequent ER visits with brief overnight staysPolice called – he bragged about a special Police called – he bragged about a special
relationship with policerelationship with policeDivalproex plus lorazepam treatment helpedDivalproex plus lorazepam treatment helpedNo evidence of alcohol nor illicit substancesNo evidence of alcohol nor illicit substancesDiagnoses at age 20 when seen:Diagnoses at age 20 when seen:
Panic disorder without agoraphobia, bipolar I, Panic disorder without agoraphobia, bipolar I, history of Tourette syndrome, OCD & autistic history of Tourette syndrome, OCD & autistic disorderdisorder
Age 21Age 21Age 21: ER visits continuedAge 21: ER visits continued
Also began drinking alcoholAlso began drinking alcohol Increased already large appetiteIncreased already large appetiteYounger roommates exploited his disability Younger roommates exploited his disability
paymentspaymentsHe & they immature acted out (stylized gang He & they immature acted out (stylized gang
though didn’t have sufficient skills for this)though didn’t have sufficient skills for this)Medications: divalproex, lorazepam, Medications: divalproex, lorazepam,
imipramineimipramine
Ages 23 to 25Ages 23 to 25
Age 23Age 23 Briefly involved with a woman Briefly involved with a woman
She ended it – intimidated by his large size: 6 ft tall >400 lbsShe ended it – intimidated by his large size: 6 ft tall >400 lbs
Hospitalized secondary to reactive depression & Hospitalized secondary to reactive depression & suicidal ideation (though far from action) suicidal ideation (though far from action)
Parents supportiveParents supportive
Age 25 Age 25 Working history: lost jobs from poor social skillsWorking history: lost jobs from poor social skills Care transferred away so contact lostCare transferred away so contact lost
Case discussionCase discussion
Infantile risk factors:Infantile risk factors: 2 cardiac arrests, likely prenatal alcohol exposure2 cardiac arrests, likely prenatal alcohol exposure Early emotional and ?nutritional deprivationsEarly emotional and ?nutritional deprivations Required separation from birth mother (who lost Required separation from birth mother (who lost
parental rights)parental rights) First degree relative familial risk for alcoholism & First degree relative familial risk for alcoholism &
bipolar disorderbipolar disorder
Positive features: removal from noxious Positive features: removal from noxious environment when young, adoption by stable environment when young, adoption by stable educated couple who remained dedicated to himeducated couple who remained dedicated to him
Diagnostic IssueDiagnostic Issue
Should the diagnosis of reactive Should the diagnosis of reactive attachment disorder have been made attachment disorder have been made instead of the early impression of autism?instead of the early impression of autism?Deprivation would have enhanced any Deprivation would have enhanced any
underlying vulnerability to autismunderlying vulnerability to autismLater did not show this; no DSM category of Later did not show this; no DSM category of
residual autism so it needed to be called residual autism so it needed to be called “history of autism”“history of autism”
Intense Exposure IssueIntense Exposure Issue
Mother and grandfather intensely involved Mother and grandfather intensely involved with him when 2 yrs oldwith him when 2 yrs old
Repetitive & stereotypic behaviors with need Repetitive & stereotypic behaviors with need for routine could mean autism diagnosis still for routine could mean autism diagnosis still with OCD as co-morbid with OCD as co-morbid Instead, we reflected transition by noting “past Instead, we reflected transition by noting “past
history of autism”history of autism”Autistic stereotypic behaviors, particularly Autistic stereotypic behaviors, particularly
fingers through the hair & finger sniffing may fingers through the hair & finger sniffing may bear on later emergence of the tics of TS. bear on later emergence of the tics of TS. TS could mean positive prognosis in autism TS could mean positive prognosis in autism
(controversial point) (controversial point)
Autism Co-morbidities iiAutism Co-morbidities ii
Onset of OCD preceded onset of TS by 4 yrs, Onset of OCD preceded onset of TS by 4 yrs, contrary to usual sequence of these often co-contrary to usual sequence of these often co-occurring conditions. occurring conditions.
Active tic symptomatology co-occurring with BD Active tic symptomatology co-occurring with BD reflected a previously described patternreflected a previously described pattern i.e., tic-severity covaried with hyperthymia-intensity & i.e., tic-severity covaried with hyperthymia-intensity &
improved with Lithium treatmentimproved with Lithium treatment
20-year followup 20-year followup (see fig)(see fig)
Rare opportunity of a 20-year continuing care & Rare opportunity of a 20-year continuing care & follow-up of a complex neurodevelopmental follow-up of a complex neurodevelopmental neuropsychiatric condition. neuropsychiatric condition. Fig shows the sequence of NN’s meeting DSM criteria Fig shows the sequence of NN’s meeting DSM criteria
for disorder onset through no longer demonstrating the for disorder onset through no longer demonstrating the range of symptoms required for the diagnosisrange of symptoms required for the diagnosis
The sx residua of one diagnostic entity may become the The sx residua of one diagnostic entity may become the sx antecedent of a subsequent dx entity or entities. sx antecedent of a subsequent dx entity or entities.
Onset/offset timing of NN’s DSM diagnoses seem Onset/offset timing of NN’s DSM diagnoses seem arbitrary. arbitrary.
Case already made for diagnosis of “history of autism”Case already made for diagnosis of “history of autism”
Patient NN Patient NN (Jacob Kerbeshian & Larry Burd)(Jacob Kerbeshian & Larry Burd)
We propose:We propose:
Progression sequence of NN’s Progression sequence of NN’s comorbid diagnoses reflects the comorbid diagnoses reflects the developmental course, or developmental course, or epigenesis, of some symptoms epigenesis, of some symptoms that comprise syndrome that comprise syndrome phenomenologyphenomenology
OCD Symptoms iOCD Symptoms i
Rapoport & Fiske noted that OCD sxs help Rapoport & Fiske noted that OCD sxs help select & control actions, ideas or concernsselect & control actions, ideas or concernsFor NN, content involved boundaries, order, For NN, content involved boundaries, order,
When very young, he showed social When very young, he showed social isolation, rocking and other repetitive, isolation, rocking and other repetitive, stereotypic behaviors, & ritualistic stereotypic behaviors, & ritualistic unimaginative play that indeed qualified him unimaginative play that indeed qualified him for the diagnosis of autism. for the diagnosis of autism.
OCD Symptoms iiOCD Symptoms ii
As time passed, social involvement ensuedAs time passed, social involvement ensued When stereotypic behaviors lessened, his room When stereotypic behaviors lessened, his room
arrangement commanded his attention arrangement commanded his attention He compulsively arranged toys & ritualized daily routines He compulsively arranged toys & ritualized daily routines
with ego-syntonic aggressive fantasieswith ego-syntonic aggressive fantasies Preoccupation with germs, dirt, and hand washing Preoccupation with germs, dirt, and hand washing
soon followed. soon followed. Televised professional wrestling fascinated him along Televised professional wrestling fascinated him along
with other heroic themes with other heroic themes Then at age 15 obsessions & compulsions Then at age 15 obsessions & compulsions
disappeared disappeared
Developmental line for autistic, Developmental line for autistic, OCD & TS symptomsOCD & TS symptoms
We suggest a psychopathological We suggest a psychopathological developmental line of autistic developmental line of autistic repetitive/stereotypic behavior/concerns repetitive/stereotypic behavior/concerns with OCD ritualistic & obsessive behaviorswith OCD ritualistic & obsessive behaviors
A similar pattern with tic symptoms of TS A similar pattern with tic symptoms of TS relates to TS as alternate expression to relates to TS as alternate expression to OCD of a common genetic diathesis OCD of a common genetic diathesis
Neuropathological developmental lineNeuropathological developmental line Autistic stereotypies lined with TS tics Autistic stereotypies lined with TS tics
Note NN’s early rocking & other stereotypies such as Note NN’s early rocking & other stereotypies such as the running of his fingers through his hair the running of his fingers through his hair
Finger sniffing followed; later simple motor & vocal Finger sniffing followed; later simple motor & vocal ticstics
He muttered & chanted to himself He muttered & chanted to himself He exhibited echolalia, ?reflecting complex vocal tic He exhibited echolalia, ?reflecting complex vocal tic
echolalia also associated with autism echolalia also associated with autism
Physical posturing expansive at times. Physical posturing expansive at times.
NN’s tics ceased by later adolescence, NN’s tics ceased by later adolescence, consistent with developmental course of this conditionconsistent with developmental course of this condition
Bipolar DisorderBipolar Disorder
Might NN’s BD reflect similar processes? Might NN’s BD reflect similar processes? After autistic stance, he showed demanding, After autistic stance, he showed demanding,
irritable behaviorsirritable behaviorsWhen school age, he told tall talesWhen school age, he told tall tales
Circumscribed interests often included grandiose Circumscribed interests often included grandiose fantasies in which he attributed to himself magical fantasies in which he attributed to himself magical powerspowers
Repetitive mumblings often included aggressive Repetitive mumblings often included aggressive fantasies – hyperverbal & expansive behavior fantasies – hyperverbal & expansive behavior ensuedensued
When a young teen, suspicions of others caused When a young teen, suspicions of others caused him to want a knife to protect himself at school him to want a knife to protect himself at school
Over time, grandiose ideas reframed to jokes Over time, grandiose ideas reframed to jokes
Questions about NN’s maniaQuestions about NN’s mania
Speculative psychopathological Speculative psychopathological developmental line for NN’s manic developmental line for NN’s manic symptoms: symptoms: Did autistic isolation transmute to affect Did autistic isolation transmute to affect
regulation problems?regulation problems?Did obsessional thoughts emerge later as Did obsessional thoughts emerge later as
grandiose ideation? grandiose ideation? Did OCD-tic like repetitive mumblings evolve Did OCD-tic like repetitive mumblings evolve
to hyperverbosity?to hyperverbosity?
Panic Disorder Panic Disorder Panic emerged as major adult symptomPanic emerged as major adult symptom
Did this have roots in common with isolation & catastrophic Did this have roots in common with isolation & catastrophic responses of his autism?responses of his autism?
Need for order and control of his OCD may have transmuted to Need for order and control of his OCD may have transmuted to worries about loss of control & panic worries about loss of control & panic
Interruptive process of his panic attacks may have stemmed Interruptive process of his panic attacks may have stemmed from the spasmodic interruptive nature of his tics from the spasmodic interruptive nature of his tics
Paranoid ideation parts of his bipolar symptoms may have Paranoid ideation parts of his bipolar symptoms may have partially determined his anxiety partially determined his anxiety
Some patients with BD & PD may reflect a shared genetic Some patients with BD & PD may reflect a shared genetic vulnerability for both disordersvulnerability for both disorders
For his panic sx, we hypothesize a psychopathological For his panic sx, we hypothesize a psychopathological developmental line with his autism, OCD, TS, & BDdevelopmental line with his autism, OCD, TS, & BD
CanalizationCanalization
Elsewhere, we applied the canalization concept Elsewhere, we applied the canalization concept to understand neuropathology & to understand neuropathology & psychopathology of Tourettes Disorderpsychopathology of Tourettes Disorder TS: developmental neuropsychiatric disorder defined TS: developmental neuropsychiatric disorder defined
by multiple motor & vocal tics for at least a year with by multiple motor & vocal tics for at least a year with onset by 18 yrs onset by 18 yrs
Much evidence suggests striatal dysfunction in TS. Much evidence suggests striatal dysfunction in TS. Genetically heterogeneous Genetically heterogeneous Those with TS possess a greater than chance Those with TS possess a greater than chance
concordance for ADHD, OCD & pervasive concordance for ADHD, OCD & pervasive developmental disorders including autism, & BDdevelopmental disorders including autism, & BD
?TS = Confluence ?TS = Confluence
For those with both TS & autism, the TS may For those with both TS & autism, the TS may reflect a neurodevelopmental confluence reflect a neurodevelopmental confluence Through which, in development, several etiologically Through which, in development, several etiologically
heterogeneous neuropsychiatric & heterogeneous neuropsychiatric & neurodevelopmental processes must pass neurodevelopmental processes must pass
A point of confluence may stem from a canalization of A point of confluence may stem from a canalization of developmental process, developmental process,
&/or a canalization of deviations or distortions from &/or a canalization of deviations or distortions from that process that process
This might similarly figure in the concordance for This might similarly figure in the concordance for TS & BD in this patientTS & BD in this patient
Canalization & StriatumCanalization & Striatum Does normal striatal function involve deep Does normal striatal function involve deep
canalization? canalization? A variety of striatal perturbations may lead to a limited A variety of striatal perturbations may lead to a limited
array of canalized neurophysiological & symptomatic array of canalized neurophysiological & symptomatic manifestations manifestations
A gradient of depth of canalization of dysfunction A gradient of depth of canalization of dysfunction might exist within that limited array might exist within that limited array
Deeply canalized dysfunctions may appear Deeply canalized dysfunctions may appear statistically as conjoined with those less deeply statistically as conjoined with those less deeply canalizedcanalized
Canalization explains resistance to variationCanalization explains resistance to variation It also infers diagnosis-specific risk at a juncture It also infers diagnosis-specific risk at a juncture
between environmental & genetic factorsbetween environmental & genetic factors
Tourettes & canalizationTourettes & canalization TS may reflect deeply canalized striatal dysfunctionTS may reflect deeply canalized striatal dysfunction
It may more likely stem from a variety of striatal perturbations It may more likely stem from a variety of striatal perturbations If true, this would account for the genetic heterogeneity of TS, If true, this would account for the genetic heterogeneity of TS, & for a greater than chance concurrence of TS with several & for a greater than chance concurrence of TS with several
conditions mediated by striatal dysfunction conditions mediated by striatal dysfunction This idea about canalization in TS essentially linear This idea about canalization in TS essentially linear
But these descriptions of “perturbation” of striatal function in TS But these descriptions of “perturbation” of striatal function in TS consistent with concepts of general systems theoryconsistent with concepts of general systems theory
Likely nonlinear dynamics also influence TS & its Likely nonlinear dynamics also influence TS & its comorbidities with all their complexitiescomorbidities with all their complexities
Epigenesis of NN’s Epigenesis of NN’s psychopathologypsychopathology
Hypothesis: Hypothesis: Implementation of neuroanatomic structures & Implementation of neuroanatomic structures &
neurophysiologic functions, as in neural neurophysiologic functions, as in neural circuits, provide blueprints for sequential circuits, provide blueprints for sequential expression of psychopathology expression of psychopathology
Reverberates with John Hughlings Jackson’s Reverberates with John Hughlings Jackson’s ideas of a hierarchically organized CNS: ideas of a hierarchically organized CNS:
Lower center actions more predictable & Lower center actions more predictable & influenced by higher centersinfluenced by higher centers
Epigenesis iiEpigenesis ii
Symptoms show a limited range Symptoms show a limited range This stems from evolutionarily determined more highly This stems from evolutionarily determined more highly
canalized neuroanatomical structure/function canalized neuroanatomical structure/function So too only a limited range of sequencing & So too only a limited range of sequencing &
expression of normal behavior & of psychopathology expression of normal behavior & of psychopathology may express the eventual structure/functionmay express the eventual structure/function
Thus perturbation of function in a specific area of the Thus perturbation of function in a specific area of the brain will probabilistically lead to a more or less brain will probabilistically lead to a more or less limited range of psychopathology, with some limited range of psychopathology, with some expressions of that psychopathology being more likely expressions of that psychopathology being more likely than others than others
Striatum Center of NN pathologiesStriatum Center of NN pathologies
Environment influence incorporated over time Environment influence incorporated over time combined with brain ontogenesis determines combined with brain ontogenesis determines form/expression of psychopathology form/expression of psychopathology
In NN, we hypothesize the striatum as the point In NN, we hypothesize the striatum as the point of confluence of perturbation affecting different of confluence of perturbation affecting different neural circuits incorporating striatal activityneural circuits incorporating striatal activity This contributed to the diathesis for the specific This contributed to the diathesis for the specific
comorbidities expressed: for autism;52,53 for comorbidities expressed: for autism;52,53 for OCD;54,55 for TS;56,57; for BD;58,59 and for OCD;54,55 for TS;56,57; for BD;58,59 and for PD.60,61 PD.60,61
NN Formulation NN Formulation (cont.)(cont.)
Influenced by neurological and psychosocial Influenced by neurological and psychosocial development, the result was a hierarchical and development, the result was a hierarchical and longitudinal pattern of comorbidities, i.e., autism, longitudinal pattern of comorbidities, i.e., autism, OCD, TS, BD, and PD.43,62 OCD, TS, BD, and PD.43,62
In other words, the range and probabilities of In other words, the range and probabilities of expression of specific psychopathologies with expression of specific psychopathologies with reference to specific enviromes turn out to be as reference to specific enviromes turn out to be as evolutionary determined and intrinsic to brain evolutionary determined and intrinsic to brain neural circuitry as are the range and neural circuitry as are the range and probabilities of normal behaviors.probabilities of normal behaviors.
Social Brain Advantage iSocial Brain Advantage i
This unique case presented with analysis This unique case presented with analysis and speculation hopefully can lead to and speculation hopefully can lead to testable hypothesestestable hypothesesThe approach fits within the broader metaphor The approach fits within the broader metaphor
of the social brain, a metaphor that aids in of the social brain, a metaphor that aids in assimilating neurobiologic findings to an assimilating neurobiologic findings to an integrating schema. integrating schema.
We have attempted assimilation of the DSM We have attempted assimilation of the DSM categorical, phenomenologic approach to a categorical, phenomenologic approach to a longitudinal, developmental schema while longitudinal, developmental schema while using the propensity of the DSM to generate using the propensity of the DSM to generate multiple co-morbidities. multiple co-morbidities.
Social Brain Advantage iiSocial Brain Advantage ii Perhaps we bring to bear the major strength of the Perhaps we bring to bear the major strength of the
biopsychosocial model to the social brain schema, biopsychosocial model to the social brain schema, namely its systems orientation. namely its systems orientation. The social brain metaphor’s de-emphasis of the psychological The social brain metaphor’s de-emphasis of the psychological
level of organization seems a weakness but even more a level of organization seems a weakness but even more a simplifying strength. simplifying strength.
We have deployed an epigenetic developmental model. We have deployed an epigenetic developmental model. And finally we emphasized an evolutionary biologic And finally we emphasized an evolutionary biologic
concept, that of canalization, as it applies to our schema. concept, that of canalization, as it applies to our schema. An important facet of the social brain metaphor, we believe, An important facet of the social brain metaphor, we believe,
hinges on its accommodation of the different approaches.hinges on its accommodation of the different approaches.
