title: Genetic markers of striatal dopamine predict individual differences in dysfunctional, but not functional impulsivity.
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.
authors.affiliation: Cognitive Psychology Unit & Leiden Institute for Brain and Cognition, Leiden University, Postbus 9555, 2300 RB, Leiden, The Netherlands. colzato@fsw.leidenuniv.nl
authors.forename: L S
authors.initials: LS
authors.lastname: Colzato
authors.forename: W P M
authors.initials: WP
authors.lastname: van den Wildenberg
authors.forename: A J W
authors.initials: AJ
authors.lastname: Van der Does
authors.forename: B
authors.initials: B
authors.lastname: Hommel
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics*; D007266:Inhibition, Psychological; D007360:Intelligence / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D057566:Self Report
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase; D004298:Dopamine