A subtle grey-matter increase in first-episode, drug-naive major depressive disorder with panic disorder after 6 weeks' duloxetine therapy

We designed this study to investigate the modulating effects of duloxetine on symptoms and grey matter of patients with major depressive disorder combined with panic disorder. We also aimed to discover if there was any persistence of grey-matter deficits after remission and to find 'trait markers' for this comorbidity. High-resolution magnetic resonance imaging and voxel-based morphometric measurements were performed on 15 patients at baseline and remitted status (week 6) compared to 15 healthy control subjects who were scanned twice within 6 wk. The rating scales of depressive and panic symptoms improved with statistical significance (corrected p < 0.001). A widespread pattern of grey-matter deficits in infero-frontal, limbic, occipital, temporo-parietal, cerebellar areas (trait marker regions) in drug-naive patients were observed compared to controls at baseline (family-wise error corrected p < 0.0002). There were no significant changes of grey matter in healthy controls over the 6-wk period. Duloxetine-induced increases of grey matter were very subtle in left infero-frontal cortex, right fusiform gyrus, and right cerebellum Villa areas (state marker regions) after 6-wk therapy (uncorrected p < 0.0005). Duloxetine did not increase grey matter to the level of control subjects and grey-matter deficits in patients appear largely unaffected by duloxetine. We suggest that short-term duloxetine therapy improved the clinical symptoms of patients with major depressive disorder combined with panic disorder. These improvements might be related to a modest increase of grey matter in state marker regions of the brain. The deficits of trait marker regions were more evident and are likely to be important for pathogenesis.