PT  - JOURNAL ARTICLE
AU  - Chao-Gan Yan
AU  - Xiao Chen
AU  - Le Li
AU  - Francisco Xavier Castellanos
AU  - Tong-Jian Bai
AU  - Qi-Jing Bo
AU  - Guan-Mao Chen
AU  - Ning-Xuan Chen
AU  - Wei Chen
AU  - Chang Cheng
AU  - Yu-Qi Cheng
AU  - Xi-Long Cui
AU  - Jia Duan
AU  - Yi-Ru Fang
AU  - Qi-Yong Gong
AU  - Wen-Bin Guo
AU  - Zheng-Hua Hou
AU  - Lan Hu
AU  - Li Kuang
AU  - Feng Li
AU  - Kai-Ming Li
AU  - Tao Li
AU  - Yan-Song Liu
AU  - Zhe-Ning Liu
AU  - Yi-Cheng Long
AU  - Qing-Hua Luo
AU  - Hua-Qing Meng
AU  - Dai-Hui Peng
AU  - Hai-Tang Qiu
AU  - Jiang Qiu
AU  - Yue-Di Shen
AU  - Yu-Shu Shi
AU  - Tian-Mei Si
AU  - Chuan-Yue Wang
AU  - Fei Wang
AU  - Kai Wang
AU  - Li Wang
AU  - Xiang Wang
AU  - Ying Wang
AU  - Xiao-Ping Wu
AU  - Xin-Ran Wu
AU  - Guang-Rong Xie
AU  - Hai-Yan Xie
AU  - Peng Xie
AU  - Xiu-Feng Xu
AU  - Hong Yang
AU  - Jian Yang
AU  - Jia-Shu Yao
AU  - Shu-Qiao Yao
AU  - Ying-Ying Yin
AU  - Yong-Gui Yuan
AU  - Ai-Xia Zhang
AU  - Hong Zhang
AU  - Ke-Rang Zhang
AU  - Lei Zhang
AU  - Zhi-Jun Zhang
AU  - Ru-Bai Zhou
AU  - Yi-Ting Zhou
AU  - Jun-Juan Zhu
AU  - Chao-Jie Zou
AU  - Xi-Nian Zuo
AU  - Jing-Ping Zhao
AU  - Yu-Feng Zang
TI  - Reduced Default Mode Network Functional Connectivity in Recurrent Patients with Major Depressive Disorder: Evidence from 25 Cohorts
AID  - 10.1101/321745
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 321745
4099  - http://biorxiv.org/content/early/2018/10/22/321745.short
4100  - http://biorxiv.org/content/early/2018/10/22/321745.full
AB  - 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. 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. We found decreased instead of increased DMN FC when comparing 848 MDDs with 794 NCs from 17 sites after data exclusion. 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. DMN FC was also positively related to symptom severity but only in recurrent MDDs. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. 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. This manuscript announces the publicly available resting-state fMRI indices of the REST-meta-MDD consortium shared via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal depression studies and to other psychiatric disorders.SIGNIFICANCE STATEMENT Functional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. By creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.