Transcript Moving Target: The Developing Social Brain

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
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Used with Permission
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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
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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
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Requirements of overarching
theory
Comprehensible to the psychiatrist
 Intuitively acceptable to the public
 Scientifically sound
 Can overcome the crude reductionism of
“biochemical imbalance”
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DSM III & precursors
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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
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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
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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
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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
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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)
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Developmental perspective
Originally from child/adolescent work
 Anna Freud pioneered developmental
lines
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Line elements follow overlapping predictable
sequences
 Distortions/deviations may lead to
psychopathology
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Erickson similar, examined adult life
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Stages incorporate antecedents from previous
stage & project to future ones
Developmental & biopsychosocial
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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
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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
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Defined: Social brain =
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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
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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
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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
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Canalization
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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
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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
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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
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Birth Parents
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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
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Adoptive parents & early life
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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
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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
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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
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Age 6 years
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Seen for first time by JK
Many unverifiable tall tales
 Identification with Darth Vader
 Compulsively arranged things in room
 Examination: large girth & general stature
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 Clumsy,
disjointed, dyspraxic
 Good eye contact with smiling
 Articulation problem; Vocabulary ok
 Expressed tantruming & annoyance
 Preoccupied with specific rules
Diagnoses age 6
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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
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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
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Acted out in play
Symptoms Age 11 years
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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
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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
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Hospitalizations at ages 15 & 16
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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
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Active interest in girls
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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
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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)
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Age 19
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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
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At age 20
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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:
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 Panic
disorder without agoraphobia, bipolar I,
history of Tourette syndrome, OCD & autistic
disorder
Age 21
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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
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Ages 23 to 25
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Age 23
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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
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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
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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”
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Intense Exposure Issue
Mother and grandfather intensely involved
with him when 2 yrs old
 Between 4 & 6 yrs, showed significant
symptomatic & developmental
improvement
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Autism Co-morbidities i
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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.
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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
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i.e., tic-severity covaried with hyperthymia-intensity &
improved with Lithium treatment
20-year followup (see fig)
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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.
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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
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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
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As time passed, social involvement ensued
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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
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Neuropathological developmental line
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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,
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consistent with developmental course of this condition
Bipolar Disorder
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Might NN’s BD reflect similar processes?
After autistic stance, he showed demanding,
irritable behaviors
 When school age, he told tall tales
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 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
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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?
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Panic Disorder
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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
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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
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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
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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
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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
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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
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Epigenesis ii
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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
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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
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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.
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Social Brain Advantage ii
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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.
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An important facet of the social brain metaphor, we believe,
hinges on its accommodation of the different approaches.