Moving Target: The

Developing Social Brain &

PsychopathologyResearch Committee

Group for the Advancement of Psychiatry (GAP)

Jacob Kerbeshian

Co-author: Larry BurdOther committee members: Russell Gardner, Beverly Sutton, John Beahrs,

Fred Wamboldt, Alan Swann, Johan Verhulst, Michael Schwartz, Morton Sosland, Carlo Carandang, Doug Kramer, John Looney

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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)

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

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”

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

Erickson similar, examined adult life

Stages incorporate antecedents from previous stage & project to future ones

Developmental & biopsychosocial

Attraction & integration of psychodynamics missed

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 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

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

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”

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, neuron-

determined behaviors more active with repetition

Case of NN – overview

Male followed from age 6 to 25 years

Presented range of DSM comorbidities

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

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:

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:

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

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 statureClumsy, 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

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

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

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

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

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

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

Working history: lost jobs from poor social skills

Care transferred away so contact lost

Case discussion

Infantile risk factors:

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

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

Onset of OCD preceded onset of TS by 4 yrs,

contrary to usual sequence of these often co-

occurring 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.

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

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 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

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

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 talesCircumscribed 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 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

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 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? 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 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

This idea about canalization in TS essentially linear 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

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

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.)

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. 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.