Anokhin Andrey P, Golosheykin Simon, Grant Julia D, Heath Andrew C
Washington University School of Medicine, St. Louis, MO, USA.
Washington University School of Medicine, St. Louis, MO, USA.
Int J Psychophysiol. 2017 May;115:112-124. doi: 10.1016/j.ijpsycho.2017.03.002. Epub 2017 Mar 12.
The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders.
抑制优势但与情境或目标不符的反应的能力对于行为的适应性自我调节至关重要。反应抑制是冲动性的一个关键组成部分,其缺陷被认为是一系列神经精神疾病(如注意力缺陷多动障碍和成瘾)的核心功能障碍。识别反应抑制神经基础中的遗传传递变异有助于阐明这些疾病的病因途径,并建立基因、大脑和行为之间的联系。然而,在青春期这个以行为自我调节薄弱为特征的发育阶段,关于遗传对反应抑制神经机制的影响知之甚少。在此,我们对一大群12岁、14岁和16岁时接受纵向评估的青少年双胞胎在Go/No-Go任务中诱发的事件相关电位(ERP)的遗传度进行了研究。遗传分析表明,在所有三个年龄阶段,与抑制相关的额叶N2和P3成分都具有显著的遗传度,个体间变异的50%至60%可归因于遗传因素。这些遗传影响包括在不同年龄活跃的常见遗传因素以及在发育过程中出现的新的遗传影响。最后,从12岁到16岁发育变化速率的个体差异受到遗传因素的显著影响。总之,本研究为青春期反应抑制的神经相关性的遗传影响提供了首个证据,并表明在Go/No-Go任务中诱发的ERP可作为研究去抑制和冲动控制障碍的中间神经生理表型(内表型)。