Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude

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We hypothesize the existence of an inherited predisposition for a spectrum of behaviors and traits characterized by behavioral disinhibition. This externalizing spectrum includes childhood disruptive disorders, antisocial behavior, substance use disorders, personality traits related to behavioral undercontrol, and the precocious expression of problem behavior. We further hypothesize that a genetically influenced central nervous system diathesis underlies this spectrum and is reflected in reduced P300 amplitude in a visual oddball event-related potential task. A review of evidence bearing on the model is derived from findings from the Minnesota Twin Family Study, a population-based, longitudinal investigation of twin youth. These findings indicate that the collection of attributes related to behavioral disinhibition is familial, heritable, and interrelated. Evidence supporting P3 amplitude reduction (P3-AR) as an index of genetic vulnerability for this externalizing spectrum includes its association with (a) familial risk for substance use and antisocial personality disorders, (b) diagnoses of childhood disruptive disorders and substance use disorders, (c) early onset of undersocialized behavior, and (d) quantitative phenotypes related to externalizing problems. In addition, the development of substance use disorders over a 3-year period is associated with P3-AR measured prior to their expression. These findings suggest that P3-AR indexes one aspect of the genetic diathesis for a spectrum of externalizing problem behavior.

Original languageEnglish (US)
Pages (from-to)147-178
Number of pages32
JournalInternational Journal of Psychophysiology
Issue number2
StatePublished - May 1 2003

Bibliographical note

Funding Information:
Supported in part by National Institute of Health grants DA 05147, DA 13240, AA 09367, and MH 65137. Keynote lecture delivered at the 11th World Congress of Psychophysiology, the Olympics of the Brain, Celebrating the 20th Anniversary of the International Organization of Psychophysiology, associated with the United Nations (New York), July 29–August 3, 2002, Montreal, Que., Canada.


  • Alcoholism
  • Antisocial Personality
  • Behavioral disinhibition
  • Childhood disruptive disorders
  • Endophenotype
  • Event-related potential
  • Nicotine dependence
  • P300
  • Personality
  • Substance use disorders


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