Dopamine transporter genotype predicts behavioural and neural measures of response inhibition
| Autor: | Hugh Garavan, Tarrant D.R. Cummins, Robert Hester, J. Hocking, Mark W. Strudwick, Ziarih Hawi, Joe Wagner, Mark A. Bellgrove, Christopher D. Chambers |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Genotype Cognitive neuroscience Polymorphism Single Nucleotide Cellular and Molecular Neuroscience Catecholamines Functional neuroimaging Dopamine Reaction Time medicine Humans Attention deficit hyperactivity disorder Molecular Biology Genetic Association Studies Dopamine transporter Dopamine Plasma Membrane Transport Proteins biology medicine.diagnostic_test Functional Neuroimaging Brain medicine.disease Magnetic Resonance Imaging Inhibition Psychological Psychiatry and Mental health Schizophrenia biology.protein Female Psychopharmacology Functional magnetic resonance imaging Psychology Neuroscience Psychomotor Performance medicine.drug |
| Zdroj: | Molecular Psychiatry. 17:1086-1092 |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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