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Twenty-Five Cohorts of Major Depressive Disorder in China: Evidence for Reduced But Not Enhanced Default Mode Network Functional Connectivity
Background: Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues.
Methods: The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD.
Outcomes: We found decreased instead of increased DMN FC in MDD compared to NCs. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration or severity. Exploratory analyses also revealed alterations of local intrinsic activity in MDD.
Interpretation: We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. All the R-fMRI indices have been made publicly available via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal MDD studies and to other psychiatric disorders.
Funding Statement: This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031 and 81371488), the Hundred Talents Program of the Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152 and Z171100000117016), Department of Science and Technology, Zhejiang Province (2015C03037).
Declaration of Interests: All the authors declare no competing financial interests.
Ethics Approval Statement: All contributed data were from studies approved by local Institutional Review Boards. Data submitted to the consortium were fully deidentified and anonymized.
Keywords: default mode network, functional connectivity, large cohorts, major depressive disorder, resting-state fMRI
Yan, Chao-Gan and Chen, Xiao and Li, Le and Castellanos, Francisco Xavier and Bai, Tong-Jian and Bo, Qi-Jing and Chen, Guan-Mao and Chen, Ning-Xuan and Chen, Wei and Cheng, Chang and Cheng, Yu-Qi and Cui, Xi-Long and Duan, Jia and Fang, Yi-Ru and Gong, Qi-Yong and Guo, Wen-Bin and Hou, Zheng-Hua and Hu, Lan and Kuang, Li and Li, Feng and Li, Kai-Ming and Li, Tao and Liu, Yan-Song and Liu, Zhe-Ning and Long, Yi-Cheng and Luo, Qing-Hua and Meng, Hua-Qing and Peng, Dai-Hui and Qiu, Hai-Tang and Qiu, Jiang and Shen, Yue-Di and Shi, Yu-Shu and Si, Tian-Mei and Wang, Chuan-Yue and Wang, Fei and Wang, Kai and Wang, Li and Wang, Xiang and Wang, Ying and Wu, Xiao-Ping and Wu, Xin-Ran and Xie, Guang-Rong and Xie, Hai-Yan and Xie, Peng and Xu, Xiu-Feng and Yang, Hong and Yang, Jian and Yao, Jia-Shu and Yao, Shu-Qiao and Yin, Ying-Ying and Yuan, Yong-Gui and Zhang, Ai-Xia and Zhang, Hong and Zhang, Ke-Rang and Zhang, Lei and Zhang, Zhi-Jun and Zhou, Ru-Bai and Zhou, Yi-Ting and Zhu, Jun-Juan and Zou, Chao-Jie and Zuo, Xi-Nian and Zhao, Jing-Ping and Zang, Yu-Feng, Twenty-Five Cohorts of Major Depressive Disorder in China: Evidence for Reduced But Not Enhanced Default Mode Network Functional Connectivity (July 25, 2018). Available at SSRN: https://ssrn.com/abstract=3220115 or http://dx.doi.org/10.2139/ssrn.3220115
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