Differential impact of manic versus depressive episode recurrence on longitudinal gray matter volume changes in bipolar disorder.

Bipolar disorder (BD) is a severe mental disorder, characterized by episodes of mania and depression. The longitudinal neurobiological impact of BD episodes on brain structure remains largely unknown. In 124 age-sex-matched participants (62 BD patients; 62 healthy controls; HCs), aged 20-62 years, we investigated the longitudinal relationship between BD episodes and whole-brain gray matter volume (GMV) changes (3 Tesla MRI) during a two-year interval, using voxel-based morphometry in SPM12/CAT12. We compared GMV trajectories between BD patients with at least one depressive or manic episode during the two-year interval, BD patients without an episode, and HCs. We explored associations between GMV changes and clinical variables, like the number and duration of depressive or manic episodes both during the two-year interval and before baseline assessment. BD patients showed GMV increases in the right exterior cerebellum with an increasing number of depressive episodes during the two-year interval. BD patients without recurrence showed GMV reductions in this area, relative to BD patients with recurrence and HCs. Notably, BD patients without recurrence exhibited greater GMV reductions during the two-year interval, the longer they had spent in a manic episode before baseline. Our findings underscore the dynamic nature of brain changes in BD. GMV increases in BD patients with recurrence may be due to acute neuroinflammatory mechanisms including glial cell proliferation, whereas GMV reductions in BD patients without recurrence may result from abnormal synaptic refinement or pruning, as a consequence of past neuroinflammation during BD episodes.