Dysfunction of brain resting-state functional networks has been widely reported in psychiatric disorders. However, the causal relationships between brain resting-state functional networks and psychiatric disorders remain largely unclear. Here we perform bidirectional two-sample Mendelian randomization (MR) analyses to investigate the causalities between 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes (n = 34,691 individuals) and 12 psychiatric disorders (n = 14,307 to 698,672 individuals). Forward MR identified 8 rsfMRI phenotypes causally associated with the risk of psychiatric disorders. For example, the increase in the connectivity of motor, subcortical-cerebellum and limbic network was associated with lower risk of autism spectrum disorder. In adddition, increased connectivity in the default mode and central executive network was associated with lower risk of post-traumatic stress disorder and depression. Reverse MR analysis revealed significant associations between 4 psychiatric disorders and 6 rsfMRI phenotypes. For instance, the risk of attention-deficit/hyperactivity disorder increases the connectivity of the attention, salience, motor and subcortical-cerebellum network. The risk of schizophrenia mainly increases the connectivity of the default mode and central executive network and decreases the connectivity of the attention network. In summary, our findings reveal causal relationships between brain functional networks and psychiatric disorders, providing important interventional and therapeutic targets for psychiatric disorders at the brain functional network level.

大脑静息态功能网络功能障碍在精神疾病中已被广泛报道。然而，大脑静息态功能网络与精神疾病之间的因果关系仍不清楚。在这里，我们进行双向双样本孟德尔随机化 (MR) 分析，以研究 191 种静息态功能磁共振成像 (rsfMRI) 表型（n  = 34,691 人）和 12 种精神疾病（n  = 14,307 至 698,672 人）之间的因果关系。前向 MR 识别出 8 种 rsfMRI 表型与精神疾病风险存在因果关系。例如，运动、皮质下小脑和边缘网络连接性的增加与自闭症谱系障碍的风险降低相关。此外，默认模式和中央执行网络的连通性增加与创伤后应激障碍和抑郁症的风险降低相关。反向 MR 分析揭示了 4 种精神疾病和 6 种 rsfMRI 表型之间的显着关联。例如，注意力缺陷/多动障碍的风险会增加注意力、显着性、运动和皮质下小脑网络的连通性。精神分裂症的风险主要是增加默认模式和中央执行网络的连通性，降低注意网络的连通性。总之，我们的研究结果揭示了脑功能网络与精神疾病之间的因果关系，为脑功能网络水平的精神疾病提供了重要的干预和治疗靶点。