Serotonin transporter gene variation and stressful life events impact processing of fear and anxiety
Serotonin transporter gene variation and stressful life events impact processing of fear and anxiety
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DOI：
10.1017/s1461145708009565
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发表时间：
2009-04-01
影响因子：
4.8
通讯作者：
Brocke, Burkhard
中科院分区：
文献类型：
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作者：
Armbruster, Diana;Moser, Dirk Alexander;Brocke, Burkhard
5-羟色胺转运体（5-HTT）的遗传变异与恐惧和焦虑相关的行为有关。杏仁核被认为在情绪调节中至关重要，并且在成像研究中，在5-HTT基因的短（S）等位基因携带者中发现了杏仁核对恐惧刺激的反应性更强。此外，杏仁核神经支配的效应系统的反应性也是特别感兴趣的。我们最近报道了5-羟色胺转运体基因（5-HTTLPR）转录控制区的功能多态性对声惊吓反射的影响。在这里，我们试图复制和扩展这些发现。106名健康志愿者在没有额外刺激的基线期间，当他们观看三种效价条件（不愉快，愉快和中性）的图片时，记录了用眨眼反应测量的强烈噪音爆发的惊吓幅度。对受试者进行三等位基因功能多态性5-HTTLPR基因分型。在复制我们以前的研究结果中，我们发现低表达S或L-G等位基因的携带者在各种条件下表现出比L-A/L-A纯合子更强的整体惊吓反应，而两个遗传群体之间的情绪惊吓调节没有差异。此外，我们发现，最近的压力生活事件的经验导致整体较高的惊吓反应和跨块惊吓习惯较少。这些结果重复并强调了5-HTTLPR的作用，并强调整体惊吓反应可能是焦虑相关行为的遗传驱动的内表型。
Genetic variation of the serotonin transporter (5-HTT) has been associated with fear- and anxiety-related behaviours. The amygdala is considered crucial in emotional modulation and stronger amygdala reactivity in response to fearful stimuli has been found in carriers of the short (S) allele of the 5-HTT gene in imaging studies. Additionally, reactivity of amygdala-innervated effectory systems is also of particular interest. We recently reported the impact of a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) on the acoustic startle reflex. Here, we attempted to replicate and extend these findings. Startle magnitudes to intense noise bursts as measured with the eyeblink response were recorded in 106 healthy volunteers during baseline without additional stimulation and while they viewed pictures of three valence conditions: unpleasant, pleasant and neutral. Subjects were genotyped for the tri-allelic functional polymorphism 5-HTTLPR. In replication of our previous findings we found that carriers of the low-expressing S or L-G alleles exhibited stronger overall startle responses across conditions than L-A/L-A homozygotes, while there were no differences in emotional startle modulation between the two genetic groups. In addition, we found that the recent experience of stressful life events resulted in overall higher startle responses and less startle habituation across blocks. The results replicate and emphasize the role of 5-HTTLPR and stress on the overall startle response as a possible genetically driven endophenotype for anxiety-related behaviour.