Intrinsic disruption of white matter microarchitecture in major depressive disorder: A voxel-based meta analysis of diffusion tensor imaging

Background: Major depressive disorder (MDD) is a prevalent and disabling mood disorder, thought to be linked with brain white matter (WM) alterations. Prior diffusion tensor imaging (DTI) studies have reported inconsistent changes in fractional anisotropy (FA) across different brain regions in MDD patients. However, none of these studies utilized raw t-map data for WM meta-analysis in MDD. Our study aims to address this gap by conducting a whole-brain-based meta-analysis of FA in MDD using Seed-based d mapping via permutation of subject images (SDM-PSI), combining reported peak coordinates and raw statistical parametric maps. Objectives: Following PRISMA guidelines, we performed a systematic search and meta-analysis to compare FA in MDD patients with healthy controls (HC). Our goal was to identify WM abnormalities in MDD, using SDM, which could shed light on the disorder's pathogenesis. Results: The meta-analysis included 39 studies with 3696 participants (2094 with MDD, 1602HC). It revealed that MDD patients, in comparison to HC, have lower FA in the corpus callosum (CC) and anterior thalamic projections (ATP). Subgroup analyses indicated that the CC is a more stable pathogenic factor in MDD. Meta-regression analyses showed no linear correlation between the mean age, percentage of female patients, duration of depression, and FA abnormalities. This suggests that WM impairments in interhemispheric connections and anterior thalamocortical circuits are significant in the pathogenesis of MDD.