White matter abnormalities in bipolar II and unipolar depression - Evidence from fixel-based analysis

Challenges in correctly identifying bipolar disorder II (BD-II) during depressive states have led to poor clinical outcomes. BD-II-specific diffusion-weighted imaging studies are lacking. This study addresses current knowledge gaps by comparing white matter (WM) integrity in BD-II and unipolar depression (UD) using fixel-based analysis (FBA).

Primary analyses compared fibre density (FD) among 33 individuals with BD-II, 50 with UD, and 51 healthy controls (HC) in 11 a priori tracts. Sensitivity analyses among unmedicated participants examined whether medication status affects the results. Exploratory analyses assessed FD in 61 remaining tracts and other FBA metrics in all tracts, as well as the effects of illness characteristics on FBA correlates.

BD-II showed reduced FD in the left superior longitudinal fasciculus I (SLFI) compared with HC, while no significant alteration was found in UD. Group differences were similar but less pronounced in unmedicated participants. Exploratory analyses showed shared FD reductions in both groups compared to HC and more widespread disruptions in BD-II than UD. In BD-II, illness duration negatively correlated with FD, while the number of lifetime BD-II depressive episodes positively correlated with the combined fibre density and cross-section measure (FDC).

Our findings provide robust evidence of fibre-density reductions in BD-II, highlighting the importance of early intervention in BD-II. While exploratory analyses showed shared WM disruptions in both disorders, BD-II displayed more widespread alterations, and WM alterations that were linked to depressive recurrence and overall illness duration. Future studies with independent and larger samples are warranted to validate these results.