Contribution of brain network connectivity in predicting effects of polygenic risk and childhood trauma on state-trait anxiety.
Contribution of brain network connectivity in predicting effects of polygenic risk and childhood trauma on state-trait anxiety.
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DOI：
10.1016/j.jpsychires.2022.06.027
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发表时间：
2022-06
影响因子：
4.8
通讯作者：
Tian Tian-Tian;Guiling Zhang;Jian Wang;Dong Liu;Chan Wan;Jicheng Fang;Di Wu;Yiran Zhou;Yuanyuan Qin;Hongquan Zhu;Yuanhao Li;Jia Li;Wenzhen Zhu
中科院分区：
文献类型：
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作者：
Tian Tian-Tian;Guiling Zhang;Jian Wang;Dong Liu;Chan Wan;Jicheng Fang;Di Wu;Yiran Zhou;Yuanyuan Qin;Hongquan Zhu;Yuanhao Li;Jia Li;Wenzhen Zhu
背景焦虑症是一种多基因遗传性疾病，常被归因于不良的环境因素。基因-环境交互作用对焦虑发生和严重程度的影响尚不清楚。大脑网络连接的基因环境对焦虑的影响的作用还没有被探索，可能是关键的了解neuropathogenesis和指导treatment.MethodsThis研究招募了177名年轻人从社区完成功能磁共振成像，儿童创伤问卷（CTQ），状态-特质焦虑评分，和整个外显子组测序。我们计算了焦虑的多基因风险评分（PRS）和CTQ总分，这是可能影响焦虑的遗传和环境因素。异常的大脑网络连接的基因-环境的影响，其协会与焦虑scores.ResultsExcept的主要影响的PRS或CTQ内的网络连接，显着的相互作用被发现在视觉网络，默认模式网络，自我参考网络和感觉运动网络的内网络连接。此外，改变的网络连接与焦虑倾向有关。特别是，CTQ对特质焦虑的影响是通过中断的感觉运动网络介导的，伴随着显着的直接影响。然而，PRS对焦虑的影响主要是通过感觉运动网络路径介导的，超过了直接的影响，并通过儿童期创伤level.ConclusionsThese网络特定的功能变化与个体基因环境风险推进我们对焦虑的精神发病机制的理解，并为临床干预提供了新的见解。
BackgroundAnxiety is usually attributed to adverse environmental factors, but it is known as a polygenic inheritance disease. Gene-environment interactions on the occurrence and severity of anxiety are still unclear. The role of brain network connectivity in the gene-environment effects on anxiety has not been explored and may be key to understanding neuropathogenesis and guiding treatment.MethodsThis study recruited 177 young adults from the community that completed functional magnetic resonance imaging, Childhood Trauma Questionnaire (CTQ), state-trait anxiety scores, and whole exome sequencing. We calculated polygenic risk score (PRS) for anxiety and the sum score of CTQ, which are genetic and environmental factors that may affect anxiety, respectively. Abnormal brain network connectivity determined by the gene-environment effects and its associations with anxiety scores were then explored.ResultsExcept for the main effect of PRS or CTQ on intra-network connectivity, significant interactions were found in intra-network connectivity of visual network, default mode network, self-reference network, and sensorimotor network. Moreover, altered network connectivity was related to anxious tendency. In particular, the effect of CTQ on trait anxiety was mediated by the disrupted sensorimotor network, accompanied by a significant direct effect. However, the PRS influence on anxiety was mainly mediated through sensorimotor network paths, which exceeded the direct influence and was moderated by childhood trauma levels.ConclusionsThese network-specific functional changes related to individual gene-environment risks advance our understanding of psychiatric pathogenesis of anxiety and provide new insights for clinical intervention.