Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium

Yicheng Long¹, Hengyi Cao², Chaogan Yan³, Xiao Chen⁴, Le Li⁴, Francisco Xavier Castellanos⁵, Tongjian Bai⁶, Qijing Bo⁷, Guanmao Chen⁸, Ningxuan Chen⁴, Wei Chen⁹, Chang Cheng¹⁰, Yuqi Cheng¹¹, Xilong Cui¹⁰, Jia Duan¹², Yiru Fang¹³, Qiyong Gong¹⁴, Wenbin Guo¹⁰, Zhenghua Hou¹⁵, Lan Hu¹⁶, Li Kuang¹⁷, Feng Li⁷, Kaiming Li¹⁴, Tao Li¹⁷, Yansong Liu¹⁸, Qinghua Luo¹⁶, Huaqing Meng¹⁶, Daihui Peng¹³, Haitang Qiu¹⁶, Jiang Qiu¹⁹, Yuedi Shen²⁰, Yushu Shi²¹, Tianmei Si²², Chuanyue Wang⁷, Fei Wang¹², Kai Wang⁶, Li Wang²², Xiang Wang¹⁰, Ying Wang⁸, Xiaoping Wu²³, Xinran Wu²¹, Chunming Xie²⁴, Guangrong Xie¹⁰, Haiyan Xie²⁵, Peng Xie²⁶, Xiufeng Xu¹¹, Hong Yang²¹, Jian Yang²⁷, Jiashu Yao⁹, Shuqiao Yao¹⁰, Yingying Yin¹⁵, Yonggui Yuan¹⁵, Aixia Zhang²⁸, Hong Zhang²³, Kerang Zhang²⁸, Lei Zhang⁴, Zhijun Zhang²³, Rubai Zhou¹³, Yiting Zhou¹⁷, Junjuan Zhu¹³, Chaojie Zou¹¹, Yufeng Zang²⁹, Jingping Zhao¹⁰, Calais Kin-Yuen Chan³⁰, Weidan Pu³¹, Zhening Liu³²

Affiliations

¹ Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China; Mental Health Institute, Central South University, Changsha, Hunan 410011, China; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
² Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06511, USA. Electronic address: hengyi.cao@yale.edu.
³ CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Magnetic Resonance Imaging Research Center and Research Center for Lifespan Development of Mind and Brain, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY 10016, USA.
⁴ CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY 10016, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
⁶ The first affiliated hospital of Anhui Medical University, Hefei, Anhui 230022, China.
⁷ Beijing Anding Hospital, Capital Medical University, Beijing 100088, China.
⁸ The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
⁹ Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
¹⁰ Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
¹¹ Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
¹² Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
¹³ Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
¹⁴ Huaxi MR Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
¹⁵ Department of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210096, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
¹⁷ Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
¹⁸ Department of Clinical Psychology, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu 215137, China.
¹⁹ Faculty of Psychology, Southwest University, Chongqing 400716, China.
²⁰ Department of Diagnostics, Affiliated Hospital, Medical School, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
²¹ Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
²² National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing 100191, China.
²³ Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
²⁴ Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, China.
²⁵ Department of Psychiatry, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
²⁶ Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
²⁷ The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
²⁸ First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
²⁹ Center for Cognition and Brain Disorders, Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang 311121, China.
³⁰ Department of Psychology, The University of Hong Kong, Hong Kong 999077, China.
³¹ Medical Psychological Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
³² Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China; Mental Health Institute, Central South University, Changsha, Hunan 410011, China. Electronic address: zhening.liu@csu.edu.cn.

PMID: 31953148
PMCID: PMC7229351
DOI: 10.1016/j.nicl.2020.102163

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium

Yicheng Long et al. Neuroimage Clin. 2020.

. 2020:26:102163.

doi: 10.1016/j.nicl.2020.102163. Epub 2020 Jan 7.

Authors

Affiliations

¹ Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China; Mental Health Institute, Central South University, Changsha, Hunan 410011, China; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
² Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06511, USA. Electronic address: hengyi.cao@yale.edu.
³ CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Magnetic Resonance Imaging Research Center and Research Center for Lifespan Development of Mind and Brain, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY 10016, USA.
⁴ CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY 10016, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
⁶ The first affiliated hospital of Anhui Medical University, Hefei, Anhui 230022, China.
⁷ Beijing Anding Hospital, Capital Medical University, Beijing 100088, China.
⁸ The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
⁹ Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
¹⁰ Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
¹¹ Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
¹² Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
¹³ Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
¹⁴ Huaxi MR Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
¹⁵ Department of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210096, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
¹⁷ Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
¹⁸ Department of Clinical Psychology, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu 215137, China.
¹⁹ Faculty of Psychology, Southwest University, Chongqing 400716, China.
²⁰ Department of Diagnostics, Affiliated Hospital, Medical School, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
²¹ Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
²² National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing 100191, China.
²³ Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
²⁴ Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, China.
²⁵ Department of Psychiatry, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
²⁶ Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
²⁷ The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
²⁸ First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
²⁹ Center for Cognition and Brain Disorders, Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang 311121, China.
³⁰ Department of Psychology, The University of Hong Kong, Hong Kong 999077, China.
³¹ Medical Psychological Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
³² Department of Psychiatry, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China; Mental Health Institute, Central South University, Changsha, Hunan 410011, China. Electronic address: zhening.liu@csu.edu.cn.

PMID: 31953148
PMCID: PMC7229351
DOI: 10.1016/j.nicl.2020.102163

Abstract

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach.

Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels.

Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10^-3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients.

Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Keywords: Connectome; Default-mode; Depression; Dynamic functional connectivity; FMRI; Temporal variability.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors report no biomedical financial interests or potential conflicts of interest related to the present work. Dr. Castellanos reports serving on the advisory board of BOL Pharma and receiving research support (study drug) from Greenwich Biosciences.

Figures

Fig 1 — **Fig. 1**
The procedures for constructing dynamic brain networks and computing dynamic network metrics. (A) The time series for all nodes were divided into a number of continuous time windows. (B) The whole-brain connectivity matrices were calculated within each window to compose a dynamic network, whose temporal variability was then estimated by average dissimilarities between different windows. (C) The dynamic brain networks were further thresholded and binarized with a range of sparsities from 10% to 50%, at which temporal clustering and temporal efficiency were estimated. TR = repetition time.

Fig 2 — **Fig. 2**
(A) Group comparison on temporal variability. (B-C) Group comparisons on the temporal correlation coefficient and characteristic temporal path length, with values at each sparsity level and average values across all sparsities (10% to 50%) both presented. (D) Partial correlations between each metric and the HAMD score, adjusted for age, sex and site effects. The error bars and shadows in (A)–(C) represent 95% confidence intervals, and all reported p values were corrected for multiple tests using the FDR method.

Fig 3 — **Fig. 3**
The nodes showing (A) a higher nodal temporal variability, (B) a lower nodal temporal correlation coefficient, and (C) a shorter nodal temporal path length in MDD patients than HCs (with FDR-corrected p < 0.05). Sizes of plots are weighted by F values. ACC = anterior cingulate cortex; dFC = dorsal frontal cortex; IPS = intraparietal sulcus; L = left hemisphere; R = right hemisphere; vmPFC = ventromedial prefrontal cortex.

Fig 4 — **Fig. 4**
Results of subgroup comparisons among the first-episode, drug-naïve (FEDN) patients, non-FEDN patients and healthy controls (HCs). The error bars represent 95% confidence intervals, and all reported p values were corrected for multiple tests using the FDR method.

See this image and copyright information in PMC

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Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium

Affiliations

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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