Gray matter abnormalities in Major Depressive Disorder: a meta-analysis of voxel based morphometry studies

Background: Voxel-based morphometry (VBM) has been widely used to quantify structural brain changes associated with Major Depressive Disorder (MDD). While some consistent findings have been reported, individual studies have also varied with respect to the key brain regions affected by the illness, and how these abnormalities are related to patients' clinical characteristics. Here, we aimed to identify those brain regions that most consistently showed gray matter anomalies in MDD, and their clinical correlates, using meta-analytic techniques.

Methods: A systematic search of VBM studies was applied in MDD. Signed differential mapping, a new coordinate based neuroimaging meta-analysis technique, was applied to data collated from a total of 23 studies comparing regional gray matter volumes of 986 MDD patients and 937 healthy controls.

Results: Gray matter was significantly reduced in a confined cluster located in the rostral anterior cingulate cortex (ACC). There were also gray matter reductions in dorsolateral and dorsomedial prefrontal cortex and decrease in the latter region was evident in patients with multiple-episodes. Amygdala and parahippocampal gray matter volumes were significantly reduced in studies including patients with comorbid anxiety disorders, as well as in first-episode/drug free samples.

Conclusions: Gray matter reduction in rostral ACC was the most consistent finding in VBM studies of MDD. The evidence for reductions in other regions within fronto-subcortical and limbic regions was less consistent. The associations between these gray matter anomalies and clinical characteristics, particularly measures relating to illness duration, suggest that chronic MDD has a robust and deleterious, albeit spatially focal, effect on brain structure.