P3 EventRelated Potential Amplitude and the Risk for Disinhibitory Behavior Disorders

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P3 Event-Related Potential Amplitude and the Risk
for Disinhibitory Behavior Disorders

• W.G. Iacono
• University of Minnesota

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Co-Contributors

• Scott Carlson Irene Elkins
• Robert Krueger Steve Malone
• Matt McGue ( many others)

Supported by NIDA NIAAA
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Theme of this Address

• Behavioral disinhibition is expressed through a
  spectrum of related psychiatric disorders,
  personality traits, and undersocialized behaviors
  with a common etiology
• Genetically influenced CNS diathesis underlies
  this spectrum
• Reduced P3 event-related potential amplitude
  indexes the genetic diathesis

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Undersocialized-Disinhibited Behaviors

• Precocious (before age 15)
• Cigarette use
• Alcohol use
• Police contact
• Drug use
• Sexual intercourse

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Externalizing Disorders

• Childhood
• Attention deficit disorder (ADHD)
• Oppositional defiant disorder (ODD)
• Conduct disorder (CD)
• Adulthood
• Antisocial personality disorder (ASPD)
• Conduct disorder
• Adult antisocial behavior (AAB)
• Substance Use Disorders
• Nicotine dependence
• Alcohol abuse and dependence
• Illicit drug abuse and dependence

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MTFS Participant Description

• MN statewide sample of twins identified from
  birth records -17 refuse
• Day-long assessment at intake at three-year
  follow-up intervals
• 17 Year Old Intake (N1,252)
• N578 boys NMZ 411 pairs
• N674 girls MDZ 215 pairs

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Results Organized to Address Two Questions

• Are these externalizing disorders etiologically
  distinct with specific behavioral
  psychophysiological risk indicators? or
• Are the disorders part of a spectrum in which
  risk is nonspecific, with each indicator
  conferring a general increase in risk distributed
  across all of the disorders?

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Are different types of early onset problem
behavior risk indicators for specific disorders
or for externalizing generally?
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Early Problem Behavior Index(Score ranges from 0
to 5)

• Count of the following before age 15
• Smoked
• Tried alcohol without parental permission
• Had contact with police
• Used illicit drugs
• Had sexual intercourse
• Behaviors occur together (average tetra-choric
  correlation .59)

McGue Iacono, Submitted
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Prevalence of Problem Behavior Before Age 15
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Probability of age-20 diagnosis as a function of
the number of early problem behaviors Male
Percent
Early Behaviors
McGue Iacono, Submitted
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Probability of age-20 diagnosis as a function of
the number of early problem behaviors Female
Percent
Early Behaviors
McGue Iacono, Submitted
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Relationship between Early Problem Behavior and
Age 20 Externalizing
McGue Iacono, Submitted
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Krueger et al. (2002)

• Proposed a hierarchical model consisting of
• Generalized externalizing factor
• Specific factors that account for distinctions
  among disorders
• Model derived from 17-year old twin data

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Factor Loadings of Externalizing Indicators
Externalizing (Disinhibitory) Psychopathology
Krueger et al. (2002)
.47
.78
.58
.71
.63
Adolescent/ Adult Antisocial
Conduct Disorder
Alcohol Dependence
Drug Dependence
(Low) Constraint
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Genetic and Environmental Contributions to
Externalizing
Krueger et al. (2002)
Non-heritable (19)
Heritable (81)
Externalizing Psychopathology
Adolescent/ Adult Antisocial
Conduct Disorder
Alcohol Dependence
Drug Dependence
(Low) Constraint
E
C E
E
E
A E
Specific Genetic (A) and Environmental Factors
(CE)
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Do SUD parents tend to have children with SUDs or
children with a full range of externalizing
disorder?

• Question asked separately for
• Alcohol dependent parents controlling for
  parental drug dependence
• Drug dependent parents controlling for alcohol
  dependence

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Parental Substance Abuse Predicts Offspring
Disorders
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Background P3 Amplitude

• Reduced P3 amplitude is associated with
  alcoholism risk (Begleiter et al., '84 Polich et
  al., '94 Hill et al., 99 Iacono et al.,02)
• Putative endophenotype
• Individual differences in P3 amplitude are
  heritable (e.g., van Beijsterveldt et al., 01
  Katsanis et al., 1997 h2.79)
• Reduced P3 amplitude is observed in other
  externalizing disorders
• Smoking (Anokhin et al., '00 Carlson et al.,
  98)
• Drug abuse (e.g., Biggins et al., '97 Branchey
  et al., '93 Carlson et al., 98)
• CD/ASPD (e.g., Bauer et al., '94, '99 Carlson et
  al., 98)

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Rotating Heads Task of Begleiter et al. (1984)
 
160 Trials
80 Trials
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Pz
P3
P4
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(No Transcript)
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Reduced P3 Is Associated with High Externalizing
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• Is P3 amplitude reduction associated with early
  problem behaviors?

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Iacono McGue, Submitted
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P3 Amplitude Reduction and Externalizing Disorders

• Each of the following two slides plots amplitude
  reduction effect sizes associated with
  externalizing
• Separately for boys and girls
• Separately for "pure" and comorbid groups
• Using a comparison group composed of adolescents
  with no externalizing disorder or affected father

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Comorbid Indicated disorderall others Pure
Indicated disorder only
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Comorbid Indicated disorderall others Pure
Indicated disorder only
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P3 Amplitude Reduction and Paternal Risk

• The following slide plots amplitude reduction
  effect sizes associated with paternal risk
• Separately for all children and those without a
  substance use disorder at 17

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All May have substance abuse Without SA Free
of substance abuse
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Do those who develop substance abuse for the
first time at age 20 have reduced P3 at age 17?

• Examine P3 amplitude at age 17 for all new cases
  at 20, new cases that were free of externalizing
  disorder at 17, and new cases with no affected
  father
• Comparison group now excludes new cases
  developing between 17-20

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Iacono et al., 2002
All all offspring No Ext no ext. dx at
intake Low risk no paternal dx
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• (Especially) Low risk control participants who
  developed a substance use disorder at age 20
  (N19) had smaller P3 at age 17 compared to
  controls who did not (N44)

t(61)2.81, plt.01)
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Summary and Conclusions

• Different types of problem behavior present
  before age 15 are nonspecific indicators of risk
  for externalizing disorders at age 20
• Different types of parental SUD confer
  nonspecific familial risk for offspring
  externalizing
• Externalizing disorders load strongly on a latent
  externalizing factor that is highly heritable
• P3 findings support the existence of a shared
  genetic vulnerability for behavioral
  disinhibition, specifically

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P3 Amplitude Summary

• Reduced P3 is associated with precocious
  expression of problem behavior
• Reduced P3 is associated with all externalizing
  disorders, even in pure non-comorbid cases
• Reduced P3-amplitude identifies spectrum risk
• Those with small P3 express the full range of
  externalizing disorders
• Children of affected fathers have reduced P3
• SUD developing at age 20 is associated with
  reduced P3 at 17

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The P3 Endophenotype

• Reduced P3 is not an alcoholism endophenotype
• Lack of specificity of P3 effect to different
  externalizing disorders is an etiologic clue, not
  a problem
• Reduced P3 may be specific to genetic risk for
  externalizing
• E.g., although schizophrenia and depression
  associated with reduced P3
• Auditory, not visual P3 (Ford, '99)
• State not trait (Mathalon et al., '00)
• Familial specificity in externalizing
• Carlson et al. poster
• Nature of P3 effect requires additional research

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Thank you!
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(No Transcript)