The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder
Authors: Chen Xiao , Lu Bin , Li Hui-Xian , Li Xue-Ying , Wang Yu-Wei , Castellanos Francisco Xavier , Cao Li-Ping , Chen Ning-Xuan , Chen Wei , Cheng Yu-Qi , Cui Shi-Xian , Deng Zhao-Yu , Fang Yi-Ru , Gong Qi-Yong , Guo Wen-Bin , Hu Zheng-Jia-Yi , Kuang Li , Li Bao-Juan , Li Le , Li Tao , Lian Tao , Liao Yi-Fan , Liu Yan-Song , Liu Zhe-Ning , Lu Jian-Ping , Luo Qing-Hua , Meng Hua-Qing , Peng Dai-Hui , Qiu Jiang , Shen Yue-Di , Si Tian-Mei , Tang Yan-Qing , Wang Chuan-Yue , Wang Fei , Wang Hua-Ning , Wang Kai , Wang Xiang , Wang Ying , Wang Zi-Han , Wu Xiao-Ping , Xie Chun-Ming , Xie Guang-Rong , Xie Peng , Xu Xiu-Feng , Yang Hong , Yang Jian , Yao Shu-Qiao , Yu Yong-Qiang , Yuan Yong-Gui , Zhang Ke-Rang , Zhang Wei , Zhang Zhi-Jun , Zhu Jun-Juan , Zuo Xi-Nian , Zhao Jing-Ping , Zang Yu-Feng ,   the DIRECT consortium, Yan Chao-Gan , Chen Xiao , Cao Li-Ping , Chen Wei , Cheng Yu-Qi , Fang Yi-Ru , Gong Qi-Yong , Guo Wen-Bin , Kuang Li , Li Bao-Juan , Li Tao , Liu Yan-Song , Liu Zhe-Ning , Lu Jian-Ping , Luo Qing-Hua , Meng Hua-Qing , Peng Dai-Hui , Qiu Jiang , Shen Yue-Di , Si Tian-Mei , Tang Yan-Qing , Wang Chuan-Yue , Wang Fei , Wang Hua-Ning , Wang Kai , Wang Xiang , Wang Ying , Wu Xiao-Ping , Xie Chun-Ming , Xie Guang-Rong , Xie Peng , Xu Xiu-Feng , Yang Hong , Yang Jian , Yao Shu-Qiao , Yu Yong-Qiang , Yuan Yong-Gui , Zhang Ke-Rang , Zhang Wei , Zhang Zhi-Jun , Zhu Jun-Juan , Zuo Xi-Nian , Zhao Jing-Ping , Zang Yu-Feng , Yan Chao-Gan 
Published: May 2022

Abstract
Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.