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Brain structural abnormalities in adult major depressive disorder revealed by voxel- and source-based morphometry: evidence from the REST-meta-MDD Consortium

Published online by Cambridge University Press:  15 February 2022

KangCheng Wang
School of Psychology, Shandong Normal University, Jinan, Shandong, China
YuFei Hu
School of Psychology, Shandong Normal University, Jinan, Shandong, China
ChaoGan Yan
CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China International Big-Data Center for Depression Research, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
MeiLing Li
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
YanJing Wu
Faculty of Foreign Languages, Ningbo University, Ningbo, Zhejiang, China
Jiang Qiu*
Faculty of Psychology, Southwest University, Chongqing 400716, China
XingXing Zhu*
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Author for correspondence: Jiang Qiu, E-mail:; XingXing Zhu, E-mail:
Author for correspondence: Jiang Qiu, E-mail:; XingXing Zhu, E-mail:



Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices.


Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations.


VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network.


Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.

Original Article
Copyright © The Author(s), 2022. Published by Cambridge University Press

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These authors contributed equally to this work.


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