Genetic Markers of Striatal Dopamine Predict Individual Differences in Dysfunctional, but Not Functional Impulsivity

Neuroscience. 2010 Oct 27;170(3):782-8. doi: 10.1016/j.neuroscience.2010.07.050. Epub 2010 Aug 1.

Abstract

Various psychiatric disorders are characterized by elevated levels of impulsivity. Although extensive evidence supports a specific role of striatal, but not frontal dopamine (DA) in human impulsivity, recent studies on genetic variability have raised some doubts on such a role. Importantly, impulsivity consists of two dissociable components that previous studies have failed to separate: functional and dysfunctional impulsivity. We compared participants with a genetic predisposition to have relatively high striatal DA levels (DAT1 9-repeat carriers, DRD2 C957T T/T homozygotes, and DRD4 7-repeat carriers) with participants with other genetic predispositions. We predicted that the first group would show high scores of dysfunctional, but not functional, self-reported impulsivity and greater difficulty in inhibiting a behavioral response to a stop-signal, a behavioral measure of impulsivity. In a sample of 130 healthy adults, we studied the relation between DAT1, DRD4, and C957T polymorphism at the DRD2 gene (polymorphisms related to striatal DA) and catechol-Omethyltransferase (COMT) Val158Met (a polymorphism related to frontal DA) on self-reported dysfunctional and functional impulsivity, assessed by the Dickman impulsivity inventory (DII), and the efficiency of inhibitory control, assessed by the stop-signal paradigm. DRD2 C957T T/T homozygotes and DRD4 7-repeat carriers indeed had significantly higher scores on self-reported dysfunctional, but not functional, impulsivity. T/T homozygotes were also less efficient in inhibiting prepotent responses. Our findings support the claim that dopaminergic variation affects dysfunctional impulsivity. This is in line with the notion that the over-supply of striatal DA might weaken inhibitory pathways, thereby enhancing the activation of, and the competition between responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Catechol O-Methyltransferase / genetics
  • Corpus Striatum / metabolism*
  • Dopamine / genetics*
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Impulsive Behavior / genetics*
  • Inhibition, Psychological
  • Intelligence / genetics
  • Male
  • Polymorphism, Genetic
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Self Report

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Genetic Markers
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Receptors, Dopamine D4
  • Catechol O-Methyltransferase
  • Dopamine