Nomura Michio, Kaneko Masayuki, Okuma Yasunobu, Nomura Jun, Kusumi Ichiro, Koyama Tsukasa, Nomura Yasuyuki
Graduate School of Education, Kyoto University, Yoshida Hon-machi, Sakyo-ku, Kyoto, Japan.
Department of Biochemistry, Graduate School of Biomedical and Health Sciences, University of Hiroshima, Minami-ku, Hiroshima, Japan.
PLoS One. 2015 Mar 16;10(3):e0119743. doi: 10.1371/journal.pone.0119743. eCollection 2015.
The serotonergic pathway has been implicated in the pathogenesis of impulsivity, and sensitivity to aversive outcomes may be linked to serotonin (5-HT) levels. Polymorphisms in the gene that encodes the serotonin transporter (5-HTT), which have differential effects on the level of serotonin transmission, display alternate responses to aversive stimuli. However, recent studies have shown that 5-HT does not affect motor function, which suggests that the functioning of the serotonin-transporter-linked polymorphic region (5-HTTLPR) does not directly affect the behavioral regulatory process itself, but instead exerts an effect via the evaluation of the potential risk associated with particular behavioral outputs. The aim of the present study was to examine the effect of specific 5-HTTLPR genotypes on the motor regulatory process, as observed during a Go/Nogo punishment feedback task. 5-HTT gene-linked promoter polymorphisms were analyzed by polymerase chain reaction, using lymphocytes from 61 healthy Japanese volunteers. Impulsivity was defined as the number of commission errors (responding when one should not) made during a Go/Nogo task. We found that the s/s genotype group made fewer impulsive responses, specifically under aversive conditions for committing such errors, compared to those in the s/l group, without affecting overall motor inhibition. These results suggest that 5-HTTLPRs do not directly affect the behavioral regulatory process itself, but may instead exert an effect on the evaluation of potential risk. The results also indicate that under such aversive conditions, decreased expression of 5-HTT may promote motor inhibitory control.
血清素能通路与冲动行为的发病机制有关,对厌恶结果的敏感性可能与血清素(5-羟色胺,5-HT)水平有关。编码血清素转运体(5-HTT)的基因多态性对血清素传递水平有不同影响,对厌恶刺激表现出不同反应。然而,最近的研究表明,5-HT并不影响运动功能,这表明血清素转运体相关多态性区域(5-HTTLPR)的功能并不直接影响行为调节过程本身,而是通过评估与特定行为输出相关的潜在风险来发挥作用。本研究的目的是在Go/Nogo惩罚反馈任务中观察特定5-HTTLPR基因型对运动调节过程的影响。使用61名健康日本志愿者的淋巴细胞,通过聚合酶链反应分析5-HTT基因相关的启动子多态性。冲动行为被定义为在Go/Nogo任务中做出的错误反应(本不应做出反应时做出反应)的数量。我们发现,与s/l基因型组相比,s/s基因型组做出的冲动反应更少,特别是在做出此类错误反应的厌恶条件下,且不影响整体运动抑制。这些结果表明,5-HTTLPR并不直接影响行为调节过程本身,而是可能对潜在风险的评估产生影响。结果还表明,在这种厌恶条件下,5-HTT表达的降低可能会促进运动抑制控制。