Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

Cummins, T.D., Hawi, Z., Hocking, J., Strudwick, M., Hester, R., Garavan, H., Wagner, J., Chambers, C.D., & Bellgrove, M.A. (2012) Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Molecular Psychiatry, 17(11), pp. 1086-1092.

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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.

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ID Code: 74085
Item Type: Journal Article
Refereed: Yes
Additional Information: Cummins, T D R Hawi, Z Hocking, J Strudwick, M Hester, R Garavan, H Wagner, J Chambers, C D Bellgrove, M A eng Research Support, Non-U.S. Gov't England 2011/08/31 06:00 Mol Psychiatry. 2012 Nov;17(11):1086-92. doi: 10.1038/mp.2011.104. Epub 2011 Aug 30.
Additional URLs:
Keywords: Adult, Brain/*physiology, Catecholamines/genetics, Dopamine Plasma Membrane Transport Proteins/*genetics, Female, Functional Neuroimaging/methods/*psychology, Genetic Association Studies/methods, Genotype, Humans, *Inhibition (Psychology), Magnetic Resonance Imaging/methods/psychology, Male, Polymorphism, Single Nucleotide, Psychomotor Performance/*physiology, Reaction Time
DOI: 10.1038/mp.2011.104
ISSN: 1476-5578
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900) > Neurosciences not elsewhere classified (110999)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > PSYCHOLOGY (170100) > Biological Psychology (Neuropsychology Psychopharmacology Physiological Psychology) (170101)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Psychology & Counselling
Deposited On: 18 Jul 2014 00:03
Last Modified: 20 Jul 2014 23:04

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