Queensland Brain Institute and School of Psychology, University of Queensland, Brisbane, Australia.
Biol Psychiatry. 2011 Jun 15;69(12):e127-43. doi: 10.1016/j.biopsych.2010.12.040. Epub 2011 Mar 11.
Executive control processes, such as sustained attention, response inhibition, and error monitoring, allow humans to guide behavior in appropriate, flexible, and adaptive ways. The consequences of executive dysfunction for humans can be dramatic, as exemplified by the large range of both neurologic and neuropsychiatric disorders in which such deficits negatively affect outcome and quality of life. Much evidence suggests that many clinical disorders marked by executive deficits are highly heritable and that individual differences in quantitative measures of executive function are strongly driven by genetic differences. Accordingly, intense research effort has recently been directed toward mapping the genetic architecture of executive control processes in both clinical (e.g., attention-deficit/hyperactivity disorder) and nonclinical populations. Here we review the extant literature on the molecular genetic correlates of three exemplar but dissociable executive functions: sustained attention, response inhibition, and error processing. Our review focuses on monoaminergic gene variants given the strong body of evidence from cognitive neuroscience and pharmacology implicating dopamine, noradrenaline, and serotonin as neuromodulators of executive function. Associations between DNA variants of the dopamine beta hydroxylase gene and measures of sustained attention accord well with cognitive-neuroanatomical models of sustained attention. Equally, functional variants of the dopamine D2 receptor gene are reliably associated with performance monitoring, error processing, and reinforcement learning. Emerging evidence suggests that variants of the dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) show promise for explaining significant variance in individual differences in both behavioral and neural measures of inhibitory control.
执行控制过程，如持续注意力、反应抑制和错误监测，使人类能够以适当、灵活和适应的方式引导行为。执行功能障碍对人类的后果可能是巨大的，例如，神经和神经精神障碍的范围广泛，这些障碍会对结果和生活质量产生负面影响。大量证据表明，许多以执行缺陷为特征的临床障碍具有高度遗传性，并且执行功能的定量测量个体差异强烈受遗传差异驱动。因此，最近人们强烈致力于绘制临床（例如，注意缺陷/多动障碍）和非临床人群中执行控制过程的遗传结构图谱。在这里，我们回顾了关于三个典型但可分离的执行功能的分子遗传相关性的现有文献：持续注意力、反应抑制和错误处理。我们的综述重点关注单胺基因变体，因为认知神经科学和药理学的大量证据表明多巴胺、去甲肾上腺素和血清素是执行功能的神经调节剂。多巴胺 β羟化酶基因的 DNA 变体与持续注意力测量之间的关联与持续注意力的认知神经解剖学模型非常吻合。同样，多巴胺 D2 受体基因的功能变体与绩效监测、错误处理和强化学习可靠相关。新出现的证据表明，多巴胺转运蛋白基因 (DAT1) 和多巴胺 D4 受体基因 (DRD4) 的变体有望解释个体差异在行为和神经抑制控制测量中的显著差异。
