Psychological, neuroimaging, and biochemical studies on functional association between impulsive behavior and the 5-HT2A receptor gene polymorphism in humans
Psychological, neuroimaging, and biochemical studies on functional association between impulsive behavior and the 5-HT2A receptor gene polymorphism in humans
复制标题
DOI：
10.1196/annals.1377.004
复制
发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Nomura, Yasuyuki
中科院分区：
文献类型：
--
作者：
Nomura, Michio;Nomura, Yasuyuki
冲动行为是由中枢神经系统（CNS）内5-羟色胺能神经传递功能障碍引起的。脑神经成像研究表明，行为抑制与腹侧额叶皮层等皮层部位的激活有关。用[F-18]阿坦色林进行正电子发射断层扫描（PET）成像以表征5-HT 2A受体结合，结果显示，从冲动性疾病中恢复的女性腹侧额叶皮质中5-HT 2A结合减少。这些临床，神经影像学和药理学研究似乎支持这一假设，即由于5-HT受体的遗传多态性神经传递的功能改变可能参与冲动行为调制。通过自我报告的方法进行评估后，有人提出5-HT 2A受体基因启动子的多态性是冲动行为的根本原因;然而，这一假设并不令人信服。我们通过评价正常志愿者的行为任务（Go/No-go任务）来研究5-HT 2A受体基因启动子的多态性是否参与冲动性攻击。应用聚合酶链反应（PCR）技术，对71例健康志愿者外周血淋巴细胞5-HT 2A受体基因启动子区进行了多态性分析。冲动性被定义为在进行/不进行任务期间记录的委托错误（当一个人不应该做出反应时）的数量;较大数量的委托错误表明抑制冲动行为的难度较大。5-HT 2A受体基因A-1438 A等位基因组的被试在Go/No-go任务的惩罚-奖励（PR）条件下比G-1438 G组的被试犯更多的委托错误。在本综述中，我们讨论并建议可能参与的5 HT 2A受体基因启动子的A-1438 A多态性在冲动行为。这一假设是通过使用行为任务测量，可以直接揭示人类的冲动行为特征进行评估。
It has been suggested that impulsive behavior is caused by dysfunctional serotonergic 5-HT neurotransmission in the central nervous system (CNS). Brain neuroimaging studies have shown that behavioral inhibition is linked to the activation of cortex sites such as the ventral frontal cortex. Positron emission tomography (PET) imaging with [F-18]altanserin to characterize 5-HT2A receptor binding revealed a reduction in 5-HT2A binding in the ventral frontal cortex in women who had recovered from impulsive diseases. These clinical, neuroimaging, and pharmacological studies appear to support the hypothesis that functional alteration of neurotransmission due to genetic polymorphisms of the 5-HT receptors may be involved in impulsive behavior modulation. Following evaluation by a self-reporting measure, it was proposed that a polymorphism in the promoter of the 5-HT2A receptor gene is the underlying cause of impulsive behavior; however, this hypothesis is not convincing. We examined whether the polymorphism in the 5-HT2A receptor gene promoter is involved in impulsive aggression by evaluating a behavioral task (Go/No-go task) in normal volunteers. The polymorphism of the 5-HT2A receptor gene promoter in lymphocytes from 71 volunteers was analyzed by using PCR. Impulsivity was defined as the number of commission errors (responding when one should not) recorded during a Go/No-go task; a larger number of commission errors indicate greater difficulty in inhibiting impulsive behavior. The subjects of the A-1438A allele group for the 5-HT2A receptor gene made more commission errors under the punishment-reward (PR)condition in a Go/No-go task than those in the G-1438G group. In the present review, we discuss and suggest the possible involvement of the A-1438A polymorphism of the 5HT2A receptor gene promoter in impulsive behavior. This hypothesis was evaluated by using a behavioral task measure that could directly reveal impulsive behavioral traits in humans.