Dopamine transporter genotype predicts behavioural and neural measures of response inhibition
Dopamine transporter genotype predicts behavioural and neural measures of response inhibition
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DOI：
10.1038/mp.2011.104
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发表时间：
2012-11-01
影响因子：
11
通讯作者：
Bellgrove, M. A.
中科院分区：
文献类型：
--
作者：
Cummins, T. D. R.;Hawi, Z.;Bellgrove, M. A.
抑制不想要的行为的能力是一种可遗传的执行功能，可能会导致注意力缺陷多动障碍（ADHD）等疾病的风险。来自药理学和认知神经科学的证据表明，反应抑制是在大脑的额纹状体回路中实例化的，其活动模式受到儿茶酚胺、多巴胺和去甲肾上腺素的调节。共有405名健康成人参与者进行了停止信号任务，反应抑制的典范措施，产生抑制的潜伏期的指数，称为停止信号反应时间（SSRT）。使用这种表型，我们测试了遗传关联，在整个常染色体儿茶酚胺基因范围内进行高密度单核苷酸多态性作图。50名参与者还接受了功能性磁共振成像，以确定相关等位基因对大脑和行为的影响。多巴胺转运蛋白基因（SLC 6A 3：rs37020; rs 460000）多态性的等位基因变异预测SSRT的个体差异，多重比较校正后。此外，在额叶区域（前额叶，上级额叶和上级内侧回）和尾状核的活动与rs37020的T-等位基因相加变化。SLC 6A 3的遗传变异对额纹状体抑制网络发展的影响可能是行为抑制障碍的关键风险机制。分子精神病学（2012）17，1086-1092; doi：10.1038/mp.2011.104;在线发表于2011年8月30日
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. Molecular Psychiatry (2012) 17, 1086-1092; doi: 10.1038/mp.2011.104; published online 30 August 2011