Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

TDR Cummins, Z Hawi, J Hocking, M Strudwick, R Hester, H Garavan, J Wagner, CD Chambers, MA Bellgrove

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

Abstract

The ability to inhibit unwanted actions is a heritable executive function that may confer risk to disorders such as attention deficit hyperactivity disorder (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests that response inhibition is instantiated within frontostriatal circuits of the brain with patterns of activity that are modulated by the catecholamines dopamine and noradrenaline. A total of 405 healthy adult participants performed the stop-signal task, a paradigmatic measure of response inhibition that yields an index of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using this phenotype, we tested for genetic association, performing high-density single-nucleotide polymorphism mapping across the full range of autosomal catecholamine genes. Fifty participants also underwent functional magnetic resonance imaging to establish the impact of associated alleles on brain and behaviour. Allelic variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020; rs460000) predicted individual differences in SSRT, after corrections for multiple comparisons. Furthermore, activity in frontal regions (anterior frontal, superior frontal and superior medial gyri) and caudate varied additively with the T-allele of rs37020. The influence of genetic variation in SLC6A3 on the development of frontostriatal inhibition networks may represent a key risk mechanism for disorders of behavioural inhibition.
Original languageEnglish
Pages (from-to)1086-1092
Number of pages7
JournalMolecular Psychiatry
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Keywords

  • dopamine
  • fMRI
  • genetics
  • noradrenaline
  • response inhibition

Cite this

Cummins, TDR ; Hawi, Z ; Hocking, J ; Strudwick, M ; Hester, R ; Garavan, H ; Wagner, J ; Chambers, CD ; Bellgrove, MA. / Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. In: Molecular Psychiatry. 2012 ; Vol. 17, No. 11. pp. 1086-1092.
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Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. / Cummins, TDR; Hawi, Z; Hocking, J; Strudwick, M; Hester, R; Garavan, H; Wagner, J; Chambers, CD; Bellgrove, MA.

In: Molecular Psychiatry, Vol. 17, No. 11, 11.2012, p. 1086-1092.

Research output: Contribution to journalArticleResearchpeer-review

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