Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies

Am J Psychiatry. 2020 May 1;177(5):422-434. doi: 10.1176/appi.ajp.2019.19050560. Epub 2020 Feb 26.


Objective: Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities.

Methods: This coordinate-based meta-analysis included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies of blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy, increased function, and decreased function in patients with major depression relative to healthy control subjects. In secondary meta-analyses, the data were grouped across primary categories, and in tertiary analyses, by medication status and absence of psychiatric comorbidity. Activation likelihood estimation was used for all analyses.

Results: A total of 92 publications reporting 152 experiments were identified, collectively representing 2,928 patients with major depressive disorder. The primary analyses detected no convergence across studies. The secondary analyses identified portions of the subgenual cingulate cortex, hippocampus, amygdala, and putamen as demonstrating convergent abnormalities. The tertiary analyses (clinical subtypes) showed improved convergence relative to the secondary analyses.

Conclusions: Coordinate-based meta-analysis identified spatially convergent structural (VBM) and functional (VBP) abnormalities in major depression. The findings suggest replicable neuroimaging features associated with major depression, beyond the transdiagnostic effects reported in previous meta-analyses, and support a continued research focus on the subgenual cingulate and other selected regions' role in depression.

Keywords: Major Depressive Disorder; Meta-Analysis; VBM; VBP; Voxel-Based Morphometry; Voxel-Based Pathophysiology.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain / pathology
  • Brain / physiopathology*
  • Depressive Disorder, Major / pathology
  • Depressive Disorder, Major / physiopathology*
  • Functional Neuroimaging
  • Humans