Investigation of habenula volume in mood disorders: A meta-analytic study

Abstract The habenula, a small brain structure involved in processing aversive stimuli, has been strongly implicated in the pathophysiology of mood disorders. While diminutions in hippocampal and medial prefrontal cortex volume have been demonstrated in individuals with a mood disorder, evidence for structural alterations in the habenula remains inconsistent. This set of meta-analyses examines whether individuals with a mood disorder show alterations in habenula volume compared to healthy controls. We conducted six meta-analyses. Two global analyses compared left and right habenula volumes between individuals with a mood disorder (MDD or BD) and healthy controls (HCs), each including 15 samples (left: 1,230 participants; right: 1,236). Four additional analyses compared MDD versus HCs and BD versus HCs for left and right volumes separately. Subgroup and meta-regression analyses tested the habenula segmentation method, medication status, and MRI resolution as moderators. The global meta-analyses pooling MDD and BD data showed small but significant volume reductions in the left ( g = −0.1367, p = .0344) and right ( g = −0.1562, p = .0409) habenula in mood disorder patients compared to controls. However, these effects did not survive correction for multiple comparisons. After correction, no significant group differences were found in the diagnosis-specific meta-analyses (MDD versus controls; BD versus controls), and no moderator analyses were significant. Current evidence points toward small habenula volume reductions in mood disorders, though findings did not withstand correction for multiple comparisons. Further high-resolution neuroimaging studies are needed to clarify habenula volume alterations in mood disorders.