Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

Cummins, T. D. R., Hawi, Z., Hocking, J., Strudwick, M., Hester, R., Garavan, H., Wagner, J., Chambers, Christopher D. ORCID: https://orcid.org/0000-0001-6058-4114 and Bellgrove, M. A. 2012. Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Molecular Psychiatry 17 , pp. 1086-1092. 10.1038/mp.2011.104

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Cardiff University Brain Research Imaging Centre (CUBRIC) Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	dopamine; fMRI; genetics; noradrenaline; response inhibition
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	18 Oct 2022 13:06
URI:	https://orca.cardiff.ac.uk/id/eprint/12318

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