Conjoint and dissociated structural and functional abnormalities in first-episode drug-naive patients with major depressive disorder: a multimodal meta-analysis

Published MRI evidence of structural and resting-state functional brain abnormalities in MDD has been inconsistent. To eliminate interference by repeated disease episodes and antidepressant treatment, we conducted the first multimodal voxel-wise meta-analysis of studies of voxel-based morphometry (VBM) and the amplitude of low-frequency fluctuation (ALFF) in first-episode drug-naive MDD patients, using the Seed-based d Mapping method (SDM). Fifteen VBM data sets and 11 ALFF data sets were included. SDM-based multimodal meta-analysis was used to highlight brain regions with both structural and functional abnormalities. This identified conjoint structural and functional abnormalities in left lateral orbitofrontal cortex and right supplementary motor area, and also dissociated abnormalities of structure (decreased grey matter in right dorsolateral prefrontal cortex and right inferior temporal gyrus; increased grey matter in right insula, right putamen, left temporal pole, and bilateral thalamus) and function (increased brain activity in left supplementary motor area, left parahippocampal gyrus, and hippocampus; decreased brain activity in right lateral orbitofrontal cortex). This study reveals a complex pattern of conjoint and dissociated structural and functional abnormalities, supporting the involvement of basal ganglia-thalamocortical circuits, representing emotional, cognitive and psychomotor abnormalities, in the pathophysiology of early-stage MDD. Specifically, this study adds to Psychoradiology, an emerging subspecialty of radiology, which seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with mental disorder.