Reduced subgenual cingulate volumes in mood disorders: A meta-analysis

Objective: Converging evidence suggests that the subgenual cingulate (SGC) is implicated in regulation of mood and in the pathophysiology of mood disorders. Our objective was to carry out the first meta-analysis of SGC volumes in patients with mood disorders. Methods: We reviewed 10 volumetric magnetic resonance imaging studies of SGC volumes in patients with unipolar depression and bipolar disorders. For meta-analysis, we used standardized differences between means (SDMs) and random effects models. In the search for sources of heterogeneity, we subdivided the studies on the basis of diagnosis and presence of family history. Results: The volumes of left and right SGC in patients with mood disorders were significantly reduced relative to healthy control subjects (SDM -0.38, 95% confidence interval [Cl] -0.67 to -0.1 and SDM -0.2, 95% Cl -0.4 to -0.007, respectively). There were significant SGC volume reductions in patients with unipolar (left SGC SDM -0.5, 95% Cl -0.92 to -0.07; right SGC SDM -0.33, 95% Cl -0.64 to -0.02,), but not bipolar, disorder. Patients with a positive family history of mood disorders showed significant left SGC volume decrease (SDM -0.52, 95% Cl -0.96 to -0.07), which was not present among subjects without family history of mood disorders. There was no association between age and SGC volumes. Conclusion: The available evidence suggests the existence of left and less robust right SGC volumetric reductions in patients with mood disorders, predominantly in those with unipolar depression. The effect size of this difference was moderate and increased in more homogeneous subgroups of patients with a positive family history. The clustering of SGC abnormalities in patients with a family history, their presence early in the illness course and their lack of progression with age make SGC a candidate for a primary vulnerability marker, although studies in unaffected high-risk subjects are missing.