Department of Psychology, Technische Universität Dresden, TU Dresden, Dresden, Germany.
Neuropsychologia. 2011 Nov;49(13):3776-85. doi: 10.1016/j.neuropsychologia.2011.09.038. Epub 2011 Oct 1.
Emerging evidence from studies using, for example, acute tryptophan depletion or investigating genetic variation of genes related to the serotonin signaling pathway suggest a role of serotonin in executive functions such as top-down attention, working memory and inhibitory control. In the current study, we aimed at extending this evidence by using the n-back task to examine working memory performance of 130 participants via behavioral and neurophysiological indices and by focusing on variations within genes encoding key regulators of the serotonergic system: the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and a repeat polymorphism in the transcriptional control region of the monoamine-oxidase gene (MAOA-uVNTR). Because serotonin and norepinephrine systems have been shown to be structurally and functionally highly interrelated, we also examined a novel polymorphism in the promoter region of the norepinephrine transporter gene (NET -3081) in anticipation of epistatic effects. We found that carriers of 5-HTTLPR and MAOA-uVNTR alleles recently implicated in executive processing showed a more efficient executive control of working memory-related performance as evidenced by reaction time, error rate as well as N2 and P3b event-related potential measures. This impact was further supported by interactions with the NET polymorphism. Linking serotonergic influence to mechanisms of inhibitory response control implicated in working memory, our results provide further support for and add new evidence concerning the importance of serotonergic neuromodulation in executive functioning.
越来越多的研究证据表明，5-羟色胺在执行功能（如自上而下的注意力、工作记忆和抑制控制）中起着重要作用，例如急性色氨酸耗竭研究或对与 5-羟色胺信号通路相关的基因遗传变异的研究。在目前的研究中，我们旨在通过使用 n-back 任务，通过行为和神经生理指标来检查 130 名参与者的工作记忆表现，并关注编码 5-羟色胺能系统关键调节因子的基因内的变异：5-羟色胺转运体基因相关多态性区域（5-HTTLPR）和单胺氧化酶基因转录控制区的重复多态性（MAOA-uVNTR），来扩展这一证据。由于已经表明 5-羟色胺和去甲肾上腺素系统在结构和功能上高度相关，我们还检查了去甲肾上腺素转运体基因（NET -3081）启动子区域的一个新多态性，以期发现上位效应。我们发现，最近与执行加工有关的 5-HTTLPR 和 MAOA-uVNTR 等位基因的携带者在工作记忆相关表现的执行控制方面表现出更高的效率，这表现在反应时间、错误率以及 N2 和 P3b 事件相关电位测量上。NET 多态性的相互作用进一步支持了这一影响。将 5-羟色胺能的影响与工作记忆中涉及抑制反应控制的机制联系起来，我们的研究结果为 5-羟色胺能神经调节在执行功能中的重要性提供了进一步的支持，并提供了新的证据。
