CNRS USR 3246, Pitié-Salpêtrière Hospital, Paris, France.
Hum Brain Mapp. 2011 Nov;32(11):1856-67. doi: 10.1002/hbm.21150. Epub 2011 Jan 18.
The short allele of the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is associated with increased amygdala activation in response to emotional stimuli. Although top-down processes may moderate this association, available evidence is conflicting, showing the genotype influence on amygdala reactivity to be either decreased or increased during emotion regulation. Because the effects of the 5-HTTLPR polymorphism on amygdala reactivity are also conditional on self-reported life stress, differences in life stress exposure may account for this apparent discrepancy. Here, we hypothesized that self-reported life stress would moderate the relationships between genotype, cognitive appraisal, and amygdala reactivity. Forty-five healthy never-depressed subjects were presented with emotional stimuli and performed two cognitive tasks: a self-referential task and an emotion-labeling task. Life-stress exposure was measured through a semistructured interview. First, there was a genotype × condition interaction in the right amygdala: short allele carriers displayed increased amygdala activation and decreased functional connectivity with the subgenual anterior cingulate cortex in self-referential processing versus emotion labeling. Second, in line with our hypothesis, there was a genotype × condition × stress interaction in bilateral amygdala the amygdala activation during self-referential processing was negatively correlated with self-reported life stress in short allele carriers and positively in individuals homozygous for the long allele, whereas an opposite pattern was observed during emotion labeling. These results confirm that the influence of the 5-HTTLPR polymorphism on amygdala reactivity is at least partially under cognitive control. Additionally, they suggest that measuring life stress exposure is a critical step when imaging genetics.
短等位基因的血清素转运体启动子区域（5-HTTLPR）多态性与情绪刺激下杏仁核的激活增加有关。尽管自上而下的过程可能会调节这种关联，但现有证据存在冲突，表明基因型对杏仁核反应性的影响在情绪调节期间要么降低，要么增加。由于 5-HTTLPR 多态性对杏仁核反应性的影响也取决于自我报告的生活压力，因此生活压力暴露的差异可能解释了这种明显的差异。在这里，我们假设自我报告的生活压力会调节基因型、认知评价和杏仁核反应性之间的关系。45 名从未抑郁的健康受试者接受了情绪刺激，并进行了两项认知任务：自我参照任务和情绪标记任务。通过半结构化访谈测量生活压力暴露。首先，右杏仁核存在基因型×条件的相互作用：短等位基因携带者在自我参照处理中显示出杏仁核激活增加和与 subgenual 前扣带回皮质的功能连接减少，而在情绪标记中则没有。其次，与我们的假设一致，在双侧杏仁核中存在基因型×条件×应激的相互作用，在自我参照处理期间的杏仁核激活与短等位基因携带者的自我报告生活压力呈负相关，而在长等位基因纯合子中呈正相关，而在情绪标记期间则观察到相反的模式。这些结果证实，5-HTTLPR 多态性对杏仁核反应性的影响至少部分受到认知控制。此外，它们表明测量生活压力暴露是影像学遗传学的关键步骤。
