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)
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, neurondetermined 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 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
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 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.
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 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
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
This idea about canalization in TS essentially linear
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
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.