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Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

Molecular Psychiatry volume 17, pages 1086–1092 (2012)Cite this article

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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.

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Acknowledgements

This work was supported by grants from the Australian Research Council (DP0770337) to MAB and CDC, and from the Australian National Health and Medical Research Council (APP1006573) to MAB, RH, ZH, HG and CDC. MAB and RH are supported by Career Development Awards from the NHMRC Australia. We thank Melany Christofidis and Elliot Lambert for assistance with data collection and Misha Byrne for assistance with preparation of figures.

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Authors and Affiliations

  1. Queensland Brain Institute and School of Psychology, University of Queensland, Brisbane, QLD, Australia

    T D R Cummins, Z Hawi, J Wagner & M A Bellgrove

  2. Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia

    J Hocking & M Strudwick

  3. Department of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia

    R Hester

  4. School of Psychology and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

    H Garavan

  5. School of Psychology, Cardiff University, Cardiff, UK

    C D Chambers

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  1. T D R Cummins
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Correspondence to M A Bellgrove.

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Competing interests

MAB has received reimbursement from Lilly Pharmaceuticals for conference travel expenses and for speaking at conferences. MAB has received speaker's fees from Jannsen Cilag and Lilly Pharmaceuticals. The remaining authors declare no conflicts of interest.

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Cummins, T., Hawi, Z., Hocking, J. et al. Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Mol Psychiatry 17, 1086–1092 (2012). https://doi.org/10.1038/mp.2011.104

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