Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers

J Psychopharmacol. 2014 Dec;28(12):1170-7. doi: 10.1177/0269881114551079. Epub 2014 Sep 18.

Abstract

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.

Keywords: Addiction; cognition; cognitive flexibility; dopamine; dopamine receptor; dopamine transport; executive functions; gambling; genetics; inhibition response; pathological gambling; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cognition*
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Gambling / genetics*
  • Gambling / psychology*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Minisatellite Repeats / genetics*
  • Neuropsychological Tests
  • Polymorphism, Genetic
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Young Adult

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases