A voxel-based meta-analysis comparing medication-naive patients of major depression with treated longer-term ill cases

Structural neuroimaging studies have identified brain areas implicated in the pathogenesis of major depressive disorder (MDD). However, findings have been inconsistent, potentially due to variable illness duration and effects of antidepressant treatment. Using a meta-analytic approach, we compared gray matter (GM) volumes in patients grouped by medication status (naïve and treated) and illness duration (early course and long-term ill) to identify potential treatment and illness duration effects on brain structure. A total of 70 studies were included, including 3682 patients and 3469 controls. The pooled analysis found frontal, temporal and limbic regions with decreased GM volume in MDD patients. Additional analyses indicated that larger GM volume in the right striatum and smaller GM volume in the right precuneus are likely to be associated with drug effects, while smaller GM volume in the right temporal gyrus may correlate with longer illness duration. Similar GM decreases in bilateral medial frontal cortex between patient subgroups suggest that this alteration may persist over the course of illness and drug treatment.