A variant C178T in the regulatory region of the serotonin receptor gene HTR3A modulates neural activation in the human amygdala
A variant C178T in the regulatory region of the serotonin receptor gene HTR3A modulates neural activation in the human amygdala
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DOI：
10.1523/jneurosci.5261-04.2005
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发表时间：
2005-07-06
影响因子：
5.3
通讯作者：
Sadato, N
中科院分区：
文献类型：
--
作者：
Iidaka, T;Ozaki, N;Sadato, N
神经生理学和神经影像学研究的证据表明，边缘系统和前额叶系统在情绪和认知中起着重要作用。当我们看到人脸时，这些结构被激活，假设我们自动评估刺激的生物学意义。大脑中的5-羟色胺（5-HT）系统与情绪和焦虑等各种行为以及神经精神疾病的生物学有关。为了研究5-HT系统与边缘系统/前额叶活动之间的联系，正常受试者（n = 26）进行功能性磁共振成像和面临的识别任务进行了基因分型的单核苷酸多态性C178T在5-羟色胺受体3型基因（HTR3A）的调节区。我们发现C/C等位基因的受试者比C/T等位基因的受试者在杏仁核、背侧和内侧前额叶皮质有更大的活动。C/C组在任务期间的反应时间也比C/T组快。在C/C组中，受试者的气质倾向与大脑活动有显著相关性。在实验的第一次运行中，右侧杏仁核和前额皮质的基因型效应最大。这些结果表明，HTR3A中的C178T变异对杏仁核活性和人脸处理具有关键影响，可能通过调节受体表达。本研究可能有助于阐明正常人群中基因、大脑和行为之间的可能联系，并可能有助于揭示神经精神疾病的生物学基础。
Converging evidence in neurophysiological and neuroimaging studies has suggested that the limbic and prefrontal systems play important roles in emotion and cognition. These structures are activated when we see a human face, assuming that we automatically evaluate the biological significance of the stimuli. The serotonin (5-HT) system within the brain has been tied to various behaviors such as mood and anxiety and to the biology of neuropsychiatric disorders. To investigate the link between the 5-HT system and limbic/prefrontal activity, normal subjects (n = 26) who underwent functional magnetic resonance imaging and faced recognition tasks were genotyped for the single nucleotide polymorphism C178T in the regulatory region of the serotonin receptor type 3 gene (HTR3A). We found that the subjects with C/C alleles had greater activity in the amygdala and dorsal and medial prefrontal cortices than those with C/T alleles. The C/C group also showed a faster reaction time during the task than the C/T group. The temperamental predisposition of the subjects had a significant correlation with brain activity in the C/C group. The genotype effect in the right amygdala and prefrontal cortex was largest during the first run of the experiment. These results indicate that the C178T variation in the HTR3A has a critical influence on the amygdaloid activity and on human face processing, probably through regulation of the receptor expression. The present study may contribute to elucidating a possible link among genes, the brain, and behavior in normal populations and may help reveal the biological basis of neuropsychiatric disorders.