Moving Target: The Developing Social Brain and Psychopathology

Moving Target: The Developing Social Brain & Psychopathology Research Committee Group for the Advancement of Psychiatry (GAP)

Jacob Kerbeshian Co-author: Larry Burd Other committee members: Russell Gardner, Beverly Sutton, John Beahrs, Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Schwartz, Morton Sosland, Carlo Carandang, Doug Kramer, John Looney

Copyright SLACK Incorporated Used with Permission Reprint web site Http://www.slackinc.com/reprints/ Jacob Kerbeshian and Larry Burd, Moving Target: The Developing Social Brain and Psychopathology, Psychiatric Annals, 35(10), pp 839-852, 2005.

Decade of the brain 

Presidential fiat: 1990 Investigative technology  Knowledge boom  Organizing framework remains lacking (research ≈ blind men & elephant) 

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Theory requisite for proper study Psychodynamics appropriately no longer guides psychiatry now  But therefore few bridges between domain of personal knowledge & neurobiology data 

Requirements of overarching theory Comprehensible to the psychiatrist  Intuitively acceptable to the public  Scientifically sound  Can overcome the crude reductionism of “biochemical imbalance” 

DSM III & precursors  

Menu-like seeming specificity Earlier editions used narrative 

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Like introductions of present editions

Documents ok but these presently used more specifically than intended   

Disorders not valid clinical diagnoses nor illnesses Rather spectra from symptom complex to disease Considered categories even when clearly dimensional

“Co-morbidities” Term used because manual omits dimensions  Original intent of DSM-III 

Focused on clinical decision-making  Not on defining “caseness” 

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Impairment & need for treatment not indicated in dx categories

Requirements for diagnostic validity Differentiation of pathology from normality  Pathological states represent statistical variations from physiological norms  Pathognomic symptom expression  Syndromal patterns 

Design & Use of DSM Designed for diagnostic gatekeeper purposes or screening  But present use involves rigid criteria for diagnosis (not just diagnostic screening)  Stems from lack of an integrating and organizing basic science for the specialty 

Biopsychosocial Model Engel’s model utilized 3 levels of organization  Reason: dualism had caused major flaws in biomedical science  BPS model fostered intrasystemic examination & cross-systemic transactions  Reciprocal & interactive causality more accurate than linear casuality (implied by bio- level employed in isolation) 

Developmental perspective Originally from child/adolescent work  Anna Freud pioneered developmental lines 

Line elements follow overlapping predictable sequences  Distortions/deviations may lead to psychopathology 

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Erickson similar, examined adult life 

Stages incorporate antecedents from previous stage & project to future ones

Developmental & biopsychosocial 

Attraction & integration of psychodynamics missed 

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Humanistic & more interesting emotionally Compelling & intellectually stimulating Incorporated developmental framework Bridged normality & psychopathology Internally consistent, self-contained features Metaphors of “biological” psychiatry reductionistic

Psychodynamics failed from lack of data-support But nothing replaced it

Social Brain Model 

Sits on the 4-legs of neurobiological research, DSM, BPS model & developmental approach  

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Each gives it utility and efficacy But neither singly nor in combination do they fulfill the function of an integrating organizing framework

Must avoid traps of self-fulfilling theory-building without empiric testability Must allow easy movement amongst levels Practitioners and patients must comprehend & accept

Additional requirements Possess humanistic value  Foster research  Show clinical practicability  Demonstrate compatibility with nosology  Define caseness in psychopathology  Position theory in biology applied to medicine  Found compelling –stimulate intellectually  Incorporate developmental framework  Bridge normality & psychopathology 

Defined: Social brain = 

Summed synergy of brain circuits subserving social function  

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Emphasis on brain of the human having evolved with environment characteristics reflected in brain Each brain having developed uniquely

Major brain function: conspecific communication  

Note similarities & contrasts on multiple brain levels Brings ethology & evolutionary science to specialty

Evolutionary science applied to psychiatry  

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Allows explanation of gender differences Conceives mind as collection of subsystems that have responded to natural selection mechanisms that solve particular problem sets Provides insights about violence Suggests hypotheses about particular disorders  

eg, ADHD as hunter-adaptation (at the expense of school-adaptation) eg, Mania is a communicational state (misdirected alpha behaviors)

Obsessive compulsive disorder Brain module evolution  Socially meaningful rituals & OCD exhibit parallelism  Brain module neuroanatomically relevant to expression of OCD  May involve selection pressures involving social order, rule, right-wrong issues  Evolutionarily “conserved” mechanisms 

Canalization  

Waddington concept (from Embryology) “Variation in resistance to change from genetic or environmental influences on the part of inherited traits”  

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Ditch analogy: on a newly graded road, earlier grooves predict later deeper ones after more rain Inherited number of limbs resist change more than extremity adaptations for locomotion & other functions

Relevance to development issues 

Predictable developmental course, neurondetermined behaviors more active with repetition

Case of NN – overview Male followed from age 6 to 25 years  Presented range of DSM comorbidities 

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Autism, OCD, Tourette sydrome, bipolar disorder, panic disorder

Chief Complaint at age 6: Oppositional behavior, temper outbursts  OCD 

Birth-Perinatal history Premature  Survived 2 cardiac arrests as neonate  In foster home for first 3 months – ?neglect  Developmental milestones left unrecorded  Natural mother displayed inadequate nurturing skills so adopted away at age 18 months 

Birth Parents 

Birth mother 19 years old at his birth,  Hearing impairment ?from congenital rubella  Alcohol dependent 

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Birth father: 25 years old at his birth  Abandoned mo & child when learned of pregnancy  Unknown family hx 

Adoptive parents & early life  

Mother health care worker; Father professional They noted after adoption: 

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Social isolation, verbal non-responsivity, gaze avoidance, lengthy episodes of repetitive rocking behavior Walked clumsily – some toe-walking Banged head in crib; seemed accident-prone Temper tantrums Disturbed routines; play featured ritualistic features

Ages 2-4 years  

At age 2 minimal language mostly uncommunicative Then age 2, lower extremity fracture with cast: 

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Mother & grandfather spent much time reading to him Remained emotionally distant but no echolalia nor pronomial reversals

At age 35 months, developed 3-word phrases At age 4 years, toilet training occurred

Developmental gains 

Between 4 & 6 years, remission of some prior problems 

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Reduced pre-sleep rocking, night terrors, & frequent awakenings

Kindergarten: Remained withdrawn & showed little initiative  Word-finding difficulties remained in evidence 

Age 6 years 

Seen for first time by JK Many unverifiable tall tales  Identification with Darth Vader  Compulsively arranged things in room  Examination: large girth & general stature 

 Clumsy,

disjointed, dyspraxic  Good eye contact with smiling  Articulation problem; Vocabulary ok  Expressed tantruming & annoyance  Preoccupied with specific rules

Diagnoses age 6 

History of autistic disorder 

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Alternative diagnosis: OCD with residual sx of autism

Oppositional defiant disorder Mood disorder NOS, manifested through temper outbursts, periods of withdrawal, sleep disturbance, excessive involvement in fantasy 

The last could also have stemmed from autistic disorder residual & neglect

Age 11 years 6th grader  Had made significant developmental gains  Grades of B and C; Tae Kwan Do lessons  Some regression at 9 when sister born 

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Pattern of impulsive aggressiveness with dramatic gestures/threats

Rich fantasy life – Rambo featured 

Acted out in play

Symptoms Age 11 years   

Need for environmental order, mannerisms Since age 8, had motor & vocal tics Perseverated when stressed 

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Would echo movie dialog

Restless sleep, early awakening with rocking Mood changes Moderately obese Hand sniffing

Age 11 dx & tx         

Tx for attentional and affective symptoms Desipramine then protyptaline with psychotherapy Became manic secondary to the TCA Dx: Bipolar I ?amplified by TCA OCD History of autistic disorder Aggressive to family dog & sister Li stabilized mood and he slept better Teased sister but not aggressive to her

Ages 13-15 Li discontinued secondary to diabetes insipidus  Clonazepam targeted mood & tic disorder  Li retried along with diuretic plus clonazepam  tolerable polyurea with sx reduction  IQ = 106; projective testing suggested bipolar disorder  Grades: Bs, Cs, Ds 

Hospitalizations at ages 15 & 16 

He picked a fight at school while exaggeratedly laughing & insulting others, then  

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Took knife to school Proclaimed he was ninja Suggested he’d torch sister’s room Banged on walls at home

Age 16: increasing irritability, grandiosity, threats & injured sister though tics now minimal; Li and clonazepam discontinued; carbamazepine used

Status at 17 

Active interest in girls 

Tried to impress them with grandiosity as wrestler

Individualized education plan to deal with “serious emotional disturbance”  More purposefully negative to parents 

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Threatened them with child protective services

Divalproex Effect 

Used after d/cing clonazepam & CPZ Reduced sx: No racing thoughts, more calmness, better sleep, better response to curfews, preoccupied with Mafia gangster in more appropriate joking manner, compliant with medication  Increased adaptation: Kept up with schoolwork, moved to nearby community for technical training, had own car, managed own funds (from social security) 

Age 19 

At 19 d/ced divalproex, feeling no need Left technical school  Briefly engaged to 16 y.o. girl  Occasional brief episodes of depression  Fragile X examined for; negative 

At age 20 

Panic attacks began Frequent ER visits with brief overnight stays  Police called – he bragged about a special relationship with police  Divalproex plus lorazepam treatment helped  No evidence of alcohol nor illicit substances  Diagnoses at age 20 when seen: 

 Panic

disorder without agoraphobia, bipolar I, history of Tourette syndrome, OCD & autistic disorder

Age 21 

Age 21: ER visits continued Also began drinking alcohol  Increased already large appetite  Younger roommates exploited his disability payments  He & they immature acted out (stylized gang though didn’t have sufficient skills for this)  Medications: divalproex, lorazepam, imipramine 

Ages 23 to 25 

Age 23 

Briefly involved with a woman 

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She ended it – intimidated by his large size: 6 ft tall >400 lbs

Hospitalized secondary to reactive depression & suicidal ideation (though far from action) Parents supportive

Age 25 

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Working history: lost jobs from poor social skills Care transferred away so contact lost

Case discussion 

Infantile risk factors: 

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2 cardiac arrests, likely prenatal alcohol exposure Early emotional and ?nutritional deprivations Required separation from birth mother (who lost parental rights) First degree relative familial risk for alcoholism & bipolar disorder

Positive features: removal from noxious environment when young, adoption by stable educated couple who remained dedicated to him

Diagnostic Issue 

Should the diagnosis of reactive attachment disorder have been made instead of the early impression of autism?

Deprivation would have enhanced any underlying vulnerability to autism  Later did not show this; no DSM category of residual autism so it needed to be called “history of autism” 

Intense Exposure Issue Mother and grandfather intensely involved with him when 2 yrs old  Between 4 & 6 yrs, showed significant symptomatic & developmental improvement 

Autism Co-morbidities i 

Repetitive & stereotypic behaviors with need for routine could mean autism diagnosis still with OCD as co-morbid 

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Instead, we reflected transition by noting “past history of autism”

Autistic stereotypic behaviors, particularly fingers through the hair & finger sniffing may bear on later emergence of the tics of TS. 

TS could mean positive prognosis in autism (controversial point)

Autism Co-morbidities ii 

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Onset of OCD preceded onset of TS by 4 yrs, contrary to usual sequence of these often cooccurring conditions.

Longitudinal comorbidity showed > than chance concurrence for autism + TS, TS + OCD, TS + BD, & TS + BD + autism.

Active tic symptomatology co-occurring with BD reflected a previously described pattern 

i.e., tic-severity covaried with hyperthymia-intensity & improved with Lithium treatment

20-year followup (see fig) 

Rare opportunity of a 20-year continuing care & follow-up of a complex neurodevelopmental neuropsychiatric condition. 

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Fig shows the sequence of NN’s meeting DSM criteria for disorder onset through no longer demonstrating the range of symptoms required for the diagnosis The sx residua of one diagnostic entity may become the sx antecedent of a subsequent dx entity or entities.

Onset/offset timing of NN’s DSM diagnoses seem arbitrary. 

Case already made for diagnosis of “history of autism”

Patient NN (Jacob Kerbeshian & Larry Burd)

We propose: Progression sequence of NN’s comorbid diagnoses reflects the developmental course, or epigenesis, of some symptoms that comprise syndrome phenomenology

OCD Symptoms i 

Rapoport & Fiske noted that OCD sxs help select & control actions, ideas or concerns For NN, content involved boundaries, order, rules, right/wrong  Socially directed themes 

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When very young, he showed social isolation, rocking and other repetitive, stereotypic behaviors, & ritualistic unimaginative play that indeed qualified him for the diagnosis of autism.

OCD Symptoms ii 

As time passed, social involvement ensued 

When stereotypic behaviors lessened, his room arrangement commanded his attention 

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He compulsively arranged toys & ritualized daily routines with ego-syntonic aggressive fantasies

Preoccupation with germs, dirt, and hand washing soon followed.

Televised professional wrestling fascinated him along with other heroic themes

Then at age 15 obsessions & compulsions disappeared

Developmental line for autistic, OCD & TS symptoms We suggest a psychopathological developmental line of autistic repetitive/stereotypic behavior/concerns with OCD ritualistic & obsessive behaviors  A similar pattern with tic symptoms of TS relates to TS as alternate expression to OCD of a common genetic diathesis 

Neuropathological developmental line 

Autistic stereotypies lined with TS tics 

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Note NN’s early rocking & other stereotypies such as the running of his fingers through his hair Finger sniffing followed; later simple motor & vocal tics He muttered & chanted to himself He exhibited echolalia, ?reflecting complex vocal tic 

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echolalia also associated with autism

Physical posturing expansive at times.

NN’s tics ceased by later adolescence, 

consistent with developmental course of this condition

Bipolar Disorder 

Might NN’s BD reflect similar processes?

After autistic stance, he showed demanding, irritable behaviors  When school age, he told tall tales 

 Circumscribed

interests often included grandiose fantasies in which he attributed to himself magical powers  Repetitive mumblings often included aggressive fantasies – hyperverbal & expansive behavior ensued  When a young teen, suspicions of others caused him to want a knife to protect himself at school  Over time, grandiose ideas reframed to jokes

Questions about NN’s mania 

Speculative psychopathological developmental line for NN’s manic symptoms: Did autistic isolation transmute to affect regulation problems?  Did obsessional thoughts emerge later as grandiose ideation?  Did OCD-tic like repetitive mumblings evolve to hyperverbosity? 

Panic Disorder 

Panic emerged as major adult symptom 

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Did this have roots in common with isolation & catastrophic responses of his autism?

Need for order and control of his OCD may have transmuted to worries about loss of control & panic Interruptive process of his panic attacks may have stemmed from the spasmodic interruptive nature of his tics Paranoid ideation parts of his bipolar symptoms may have partially determined his anxiety Some patients with BD & PD may reflect a shared genetic vulnerability for both disorders

For his panic sx, we hypothesize a psychopathological developmental line with his autism, OCD, TS, & BD

Canalization 

Elsewhere, we applied the canalization concept to understand neuropathology & psychopathology of Tourettes Disorder 

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TS: developmental neuropsychiatric disorder defined by multiple motor & vocal tics for at least a year with onset by 18 yrs Much evidence suggests striatal dysfunction in TS. Genetically heterogeneous Those with TS possess a greater than chance concordance for ADHD, OCD & pervasive developmental disorders including autism, & BD

?TS = Confluence 

For those with both TS & autism, the TS may reflect a neurodevelopmental confluence 

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Through which, in development, several etiologically heterogeneous neuropsychiatric & neurodevelopmental processes must pass A point of confluence may stem from a canalization of developmental process, &/or a canalization of deviations or distortions from that process

This might similarly figure in the concordance for TS & BD in this patient

Canalization & Striatum 

Does normal striatal function involve deep canalization? 

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A variety of striatal perturbations may lead to a limited array of canalized neurophysiological & symptomatic manifestations A gradient of depth of canalization of dysfunction might exist within that limited array Deeply canalized dysfunctions may appear statistically as conjoined with those less deeply canalized

Canalization explains resistance to variation It also infers diagnosis-specific risk at a juncture between environmental & genetic factors

Tourettes & canalization 

TS may reflect deeply canalized striatal dysfunction  

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This idea about canalization in TS essentially linear 

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It may more likely stem from a variety of striatal perturbations If true, this would account for the genetic heterogeneity of TS, & for a greater than chance concurrence of TS with several conditions mediated by striatal dysfunction But these descriptions of “perturbation” of striatal function in TS consistent with concepts of general systems theory

Likely nonlinear dynamics also influence TS & its comorbidities with all their complexities

Epigenesis of NN’s psychopathology 

Hypothesis: Implementation of neuroanatomic structures & neurophysiologic functions, as in neural circuits, provide blueprints for sequential expression of psychopathology  Reverberates with John Hughlings Jackson’s ideas of a hierarchically organized CNS:  Lower center actions more predictable & influenced by higher centers 

Epigenesis ii 

Symptoms show a limited range  

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This stems from evolutionarily determined more highly canalized neuroanatomical structure/function So too only a limited range of sequencing & expression of normal behavior & of psychopathology may express the eventual structure/function Thus perturbation of function in a specific area of the brain will probabilistically lead to a more or less limited range of psychopathology, with some expressions of that psychopathology being more likely than others

Striatum Center of NN pathologies 

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Environment influence incorporated over time combined with brain ontogenesis determines form/expression of psychopathology In NN, we hypothesize the striatum as the point of confluence of perturbation affecting different neural circuits incorporating striatal activity 

This contributed to the diathesis for the specific comorbidities expressed: for autism;52,53 for OCD;54,55 for TS;56,57; for BD;58,59 and for PD.60,61

NN Formulation (cont.) 

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Influenced by neurological and psychosocial development, the result was a hierarchical and longitudinal pattern of comorbidities, i.e., autism, OCD, TS, BD, and PD.43,62 In other words, the range and probabilities of expression of specific psychopathologies with reference to specific enviromes turn out to be as evolutionary determined and intrinsic to brain neural circuitry as are the range and probabilities of normal behaviors.

Social Brain Advantage i 

This unique case presented with analysis and speculation hopefully can lead to testable hypotheses The approach fits within the broader metaphor of the social brain, a metaphor that aids in assimilating neurobiologic findings to an integrating schema.  We have attempted assimilation of the DSM categorical, phenomenologic approach to a longitudinal, developmental schema while using the propensity of the DSM to generate multiple co-morbidities. 

Social Brain Advantage ii 

Perhaps we bring to bear the major strength of the biopsychosocial model to the social brain schema, namely its systems orientation. 

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The social brain metaphor’s de-emphasis of the psychological level of organization seems a weakness but even more a simplifying strength.

We have deployed an epigenetic developmental model.

And finally we emphasized an evolutionary biologic concept, that of canalization, as it applies to our schema. 

An important facet of the social brain metaphor, we believe, hinges on its accommodation of the different approaches.