Serotonin transporter genetic variation and the response of the human amygdala
Serotonin transporter genetic variation and the response of the human amygdala
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DOI：
10.1126/science.1071829
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发表时间：
2002-07-19
期刊：
影响因子：
56.9
通讯作者：
Weinberger, DR
中科院分区：
文献类型：
--
作者：
Hariri, AR;Mattay, VS;Weinberger, DR
人类5-羟色胺转运体基因（SLC 6A 4）启动子区的功能多态性与神经质和精神病理学的几个方面相关，特别是焦虑特征，但这种基因型对这些复杂行为的预测价值一直不一致。血清素[5-羟色胺，（5-HT）]功能影响正常的恐惧以及病理性焦虑，在动物模型和临床研究中，行为严重依赖于杏仁核。我们现在报告的个人与一个或两个拷贝的短等位基因的5-羟色胺转运体（5-HTT）启动子多态性，这已与减少5-HTT的表达和功能，增加恐惧和焦虑相关的行为，表现出更大的杏仁核神经元活动，通过BOLD功能磁共振成像评估，在响应可怕的刺激与个人纯合子的长等位基因。这些结果表明，人类情绪行为背后的大脑区域的反应存在遗传驱动的变化，并表明杏仁核对情绪刺激的不同兴奋性可能导致通常与短SLC 6A 4等位基因相关的恐惧和焦虑增加。
A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5-hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.