Connectomics-based resting-state functional network alterations predict suicidality in major depressive disorder
Authors: Wang Qing , He Cancan , Wang Zan , Fan Dandan , Zhang Zhijun , Xie Chunming ,   on behalf of REST-meta-MDD Consortium, Yan Chao-Gan , Chen Xiao , Li Le , Castellanos Francisco Xavier , Bai Tong-Jian , Bo Qi-Jing , Chen Guan-Mao , Chen Ning-Xuan , Chen Wei , Cheng Chang , Cheng Yu-Qi , Cui Xi-Long , Duan Jia , Fang Yi-Ru , Gong Qi-Yong , Guo Wen-Bin , Hou Zheng-Hua , Hu Lan , Kuang Li , Li Feng , Li Kai-Ming , Li Tao , Liu Yan-Song , Liu Zhe-Ning , Long Yi-Cheng , Luo Qing-Hua , Meng Hua-Qing , Peng Dai-Hui , Qiu Hai-Tang , Qiu Jiang , Shen Yue-Di , Shi Yu-Shu , Wang Chuan-Yue , Wang Fei , Wang Kai , Wang Li , Wang Xiang , Wang Ying , Wu Xiao-Ping , Wu Xin-Ran , Xie Guang-Rong , Xie Hai-Yan , Xie Peng , Xu Xiu-Feng , Yang Hong , Yang Jian , Yao Jia-Shu , Yao Shu-Qiao , Yin Ying-Ying , Yuan Yong-Gui , Zhang Ai-Xia , Zhang Hong , Zhang Ke-Rang , Zhang Lei , Zhou Ru-Bai , Zhou Yi-Ting , Zhu Jun-Juan , Zou Chao-Jie , Si Tian-Mei , Zuo Xi-Nian , Zhao Jing-Ping , Zang Yu-Feng 
Published: November 2023

Suicidal behavior is a major concern for patients who suffer from major depressive disorder (MDD). However, dynamic alterations and dysfunction of resting-state networks (RSNs) in MDD patients with suicidality have remained unclear. Thus, we investigated whether subjects with different severity of suicidal ideation and suicidal behavior may have different disturbances in brain RSNs and whether these changes could be used as the diagnostic biomarkers to discriminate MDD with or without suicidal ideation and suicidal behavior. Then a multicenter, cross-sectional study of 528 MDD patients with or without suicidality and 998 healthy controls was performed. We defined the probability of dying by the suicide of the suicidality components as a ‘suicidality gradient’. We constructed ten RSNs, including default mode (DMN), subcortical (SUB), ventral attention (VAN), and visual network (VIS). The network connections of RSNs were analyzed among MDD patients with different suicidality gradients and healthy controls using ANCOVA, chi-squared tests, and network-based statistical analysis. And support vector machine (SVM) model was designed to distinguish patients with mild-to-severe suicidal ideation, and suicidal behavior. We found the following abnormalities with increasing suicidality gradient in MDD patients: within-network connectivity values initially increased and then decreased, and one-versus-other network values decreased first and then increased. Besides, within- and between-network connectivity values of the various suicidality gradients are mainly negatively correlated with HAMD anxiety and positively correlated with weight. We found that VIS and DMN-VIS values were affected by age (p < 0.05), cingulo-opercular network, and SUB-VAN values were statistically influenced by sex (p < 0.05). Furthermore, the SVM model could distinguish MDD patients with different suicidality gradients (AUC range, 0.73–0.99). In conclusion, we have identified that disrupted brain connections were present in MDD patients with different suicidality gradient. These findings provided useful information about the pathophysiological mechanisms of MDD patients with suicidality.