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

AbstractObjective: Imaging studies of major depressive disorder (MDD) have reported structural and functional abnormalities in many, 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 apply a novel, multi-modal, meta-analytic approach to test the hypothesis that MDD exhibits spatially convergent structural and functional brain abnormalities.Methods: This coordinate-based meta-analysis (CBMA) included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies imaging blood flow (BF), glucose metabolism, regional homogeneity (ReHo), and amplitude of low frequency fluctuations (ALFF/fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy; increased function; and, decreased function in MDD patients relative to healthy controls. Secondary meta-analyses grouped across primary categories. Tertiary analyses grouped by medication status and absence of psychiatric comorbidity. Activation likelihood estimation (ALE) was used for all analyses.Results: In total 92 publications reporting 152 experiments were identified, collectively representing 2,928 MDD patients. Primary analyses detected no convergence across studies. Secondary analyses identified portions of subgenual cingulate, hippocampus, amygdala, putamen, retrosplenial cortex, and middle occipital/inferior temporal gyri as demonstrating convergent abnormalities. Tertiary analyses (clinical subtypes) showed improved convergence relative to secondary analyses.Conclusions: CBMA identified spatially convergent structural (VBM) and functional (VBP) abnormalities in MDD. Present findings suggest replicable neuroimaging features associated with MDD, beyond the transdiagnostic effects reported in prior meta-analysis. Our findings support continued research focus on the subgenual cingulate and other select regions’ role in MDD