Cerebellar morphological differences and associations with extrinsic factors in bipolar disorder type I.

Background: The neural underpinnings of bipolar disorder (BD) remain poorly understood. The cerebellum is ideally positioned to modulate emotional regulation circuitry yet has been understudied in BD. Literature suggests differences in cerebellar activity and metabolism in BD, however findings on structural differences remain contradictory. Potential reasons include combining BD subtypes, small sample sizes, and potential moderators such as genetics, adverse childhood experiences (ACEs), and pharmacotherapy.

Methods: We collected 3 T MRI scans from participants with (N = 131) and without (N = 81) BD type I, as well as blood and questionnaires. We assessed differences in cerebellar volumes and explored potentially influential factors.

Results: The cerebellar cortex was smaller bilaterally in participants with BD. Polygenic propensity score did not predict any cerebellar volumes, suggesting that non-genetic factors may have greater influence on the cerebellar volume difference we observed in BD. Proportionate cerebellar white matter volumes appeared larger with more ACEs, but this may result from reduced ICV. Time from onset and symptom burden were not associated with cerebellar volumes. Finally, taking sedatives was associated with larger cerebellar white matter and non-significantly larger cortical volume.

Limitations: This study was cross-sectional, limiting interpretation of possible mechanisms. Most of our participants were White, which could limit the generalizability. Additionally, we did not account for potential polypharmacy interactions.

Conclusions: These findings suggest that external factors, such as sedatives and childhood experiences, may influence cerebellum structure in BD and may mask underlying differences. Accounting for such variables may be critical for consistent findings in future studies.