Anterior cingulate volumes in never-treated patients with major depressive disorder.

The anterior cingulate cortex (ACC) is implicated in the cognitive and affective abnormalities observed in mood disorders. Bilateral ACC volume reductions have been reported in patients with major depressive disorder (MDD) when compared to healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24(sg)), subcallosal gyrus (BA25), and paracingulate gyrus (BA32) in 65 patients receiving a first course of treatment for MDD and 93 healthy control subjects. Patients with more than three episodes of untreated MDD had smaller subcallosal gyrus volumes than healthy controls, while those with three or fewer past untreated episodes did not differ from controls. We also found preliminary evidence that medication-exposed patients had smaller SGPFC volumes than patients with no exposure to medication and healthy controls. There was no evidence that these effects related to mood state, duration of untreated illness, or to patient age. No differences were apparent in paracingulate gyrus volumes between patients and controls. These findings confirm the presence of ACC volume reductions in untreated patients with MDD and suggest that illness burden and short-term medication exposure mediate this change.