Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Hum Brain Mapp. 2023 Jun 15;44(9):3730-3743. doi: 10.1002/hbm.26308. Epub 2023 Apr 12.
Anxiety is characterized by altered brain networks. Directional information flows among dynamic brain networks concerning neuropathogenesis of anxiety have not yet been investigated. The role of directional influences between networks in gene-environment effects on anxiety remains to be further elucidated. In a large community sample, this resting-state functional MRI study estimated dynamic effective connectivity among large-scale brain networks based on a sliding-window approach and Granger causality analysis, providing dynamic and directional information for signal transmission in networks. We first explored altered effective connectivity among networks related to anxiety in distinct connectivity states. Due to the potential gene-environment effects on brain and anxiety, we further performed mediation and moderated mediation analyses to investigate the role of altered effective connectivity networks in relationships between polygenic risk scores, childhood trauma, and anxiety. State and trait anxiety scores showed correlations with altered effective connectivity among extensive networks in distinct connectivity states (p < .05, uncorrected). Only in a more frequent and strongly connected state, there were significant correlations between altered effective connectivity networks and trait anxiety (P <0.05). Furthermore, mediation and moderated mediation analyses showed that the effective connectivity networks played a mediating role in the effects of childhood trauma and polygenic risk on trait anxiety. State-dependent effective connectivity changes among brain networks were significantly related to trait anxiety, and mediated gene-environment effects on trait anxiety. Our work sheds novel light on the neurobiological mechanisms underlying anxiety, and provides new insights into early objective diagnosis and intervention evaluation.
焦虑的特征是大脑网络的改变。关于焦虑的神经发病机制，动态大脑网络之间的定向信息流尚未被研究。在基因-环境对焦虑的影响中，网络之间的定向影响的作用仍有待进一步阐明。在一个大型社区样本中，这项静息态功能磁共振成像研究基于滑动窗口方法和格兰杰因果分析，估计了大尺度脑网络之间的动态有效连接，为网络中的信号传递提供了动态和定向信息。我们首先探索了在不同连接状态下与焦虑相关的网络之间改变的有效连接。由于基因-环境对大脑和焦虑的潜在影响，我们进一步进行了中介和调节中介分析，以研究改变的有效连接网络在多基因风险评分、儿童创伤和焦虑之间关系中的作用。状态和特质焦虑评分与不同连接状态下广泛网络之间改变的有效连接存在相关性（p<0.05，未校正）。只有在更频繁和连接更强的状态下，改变的有效连接网络与特质焦虑之间才存在显著相关性（P<0.05）。此外，中介和调节中介分析表明，有效连接网络在儿童创伤和多基因风险对特质焦虑的影响中发挥了中介作用。脑网络中状态依赖的有效连接变化与特质焦虑显著相关，并介导了基因-环境对特质焦虑的影响。我们的工作为焦虑的神经生物学机制提供了新的见解，并为早期客观诊断和干预评估提供了新的思路。
