Zhang Lin, Liu Ling, Li Xueting, Song Yiying, Liu Jia
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.
Hum Brain Mapp. 2015 Jul;36(7):2732-42. doi: 10.1002/hbm.22803. Epub 2015 Apr 2.
A functional polymorphism (5-hydroxytryptamine transporter linked polymorphic region [5-HTTLPR]) in the promoter region of human serotonin transporter gene has been found to be associated with several dimensions of neuroticism and psychopathology, especially anxiety. However, the neural basis underlying the association between 5-HTTLPR and anxiety is less clear. Here, we explored how 5-HTTLPR influenced anxiety by modulating the spontaneous brain activities in Han Chinese. First, we found an association between 5-HTTLPR and anxiety only in the male and not in the female population, where male S/S homozygotes had a significantly higher level of anxiety than male L allele carriers. Then, we examined how 5-HTTLPR influenced anxiety at both regional and network levels in the brain at rest. At the regional level, we found a significantly higher fractional amplitude of low-frequency fluctuations in the amygdala in male S/S homozygotes relative to male L allele carriers. At the network level, male S/S homozygotes showed a weaker resting-state functional connectivity (RSFC) between the amygdala and various regions, including the insula, Heschl's gyrus, lateral occipital cortex, superior temporal gyrus, and hippocampus, and a stronger RSFC between the amygdala and various regions, including the supramariginal gyrus and middle frontal gyrus. However, at both levels, only was the amygdala-insula RSFC correlated with anxiety. Mediation analyses further revealed that the amygdala-insula RSFC mediated the association between 5-HTTLPR and anxiety. In short, our study provided the first empirical evidence that the amygdala-insula RSFC served as the neural basis underlying the association between 5-HTTLPR and anxiety, suggesting a potential neurogenetic susceptibility mechanism for anxiety.
人类血清素转运体基因启动子区域的一个功能性多态性（5-羟色胺转运体连锁多态性区域[5-HTTLPR]）已被发现与神经质和精神病理学的多个维度相关，尤其是焦虑。然而，5-HTTLPR与焦虑之间关联的神经基础尚不清楚。在此，我们探讨了5-HTTLPR如何通过调节汉族人的大脑自发活动来影响焦虑。首先，我们发现5-HTTLPR与焦虑的关联仅存在于男性群体中，而不存在于女性群体中，男性S/S纯合子的焦虑水平显著高于携带L等位基因的男性。然后，我们研究了5-HTTLPR在静息状态下如何在区域和网络水平上影响大脑中的焦虑。在区域水平上，我们发现男性S/S纯合子杏仁核低频波动的分数振幅相对于携带L等位基因的男性显著更高。在网络水平上，男性S/S纯合子在杏仁核与包括脑岛、颞横回、枕外侧皮质、颞上回和海马体在内的各个区域之间表现出较弱的静息态功能连接（RSFC），而在杏仁核与包括缘上回和额中回在内的各个区域之间表现出较强的RSFC。然而，在两个水平上，只有杏仁核-脑岛RSFC与焦虑相关。中介分析进一步表明，杏仁核-脑岛RSFC介导了5-HTTLPR与焦虑之间的关联。简而言之，我们的研究提供了首个实证证据，表明杏仁核-脑岛RSFC是5-HTTLPR与焦虑之间关联的神经基础，提示了一种潜在的焦虑神经遗传易感性机制。
