Abstract

Altered function in the limbic–cortical–striatial–pallidal–thalamic (LCSPT) circuit has been implicated in the pathophysiology of major depressive disorder (MDD). This study evaluated volumetric differences in subcortical volumes between depressed subjects with MDD (N=142), subjects with MDD in remission (N=72), and healthy controls (N=169). Participants underwent magnetic resonance imaging (MRI) scanning, and subcortical volumes were extracted using FMRIB's Integrated Registration and Segmentation Tool (FIRST), University of Oxford, UK. The depressed MDD subjects exhibited significantly smaller volumes in the bilateral thalamus and hippocampus compared to control subjects, and the differences in the bilateral thalamus remained significant after controlling for total intracranial volume. In a smaller subset of healthy controls and depressed MDD subjects matched to the remitted MDD subjects, significant differences in volume were observed across groups in the bilateral thalamus, as well as the right lateralized caudate, hippocampus, and pallidum; these were primarily accounted for by differences between the depressed MDD subjects versus both the remitted and healthy subjects, though none of these changes remained significant after controlling for total intracranial volume (TIV). Volumetric reductions in the thalamus and hippocampus may contribute to dysfunction within subcortical–cortical networks, consistent with previous evidence of metabolic and hemodynamic abnormalities in these regions in MDD.

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