White Matter Abnormalities in Bipolar II and Unipolar Depression - Evidence from Fixel-Based Analysis.

Background: Challenges in correctly identifying bipolar II disorder (BD-II) during depressive states have led to poor clinical outcomes. BD-II-specific imaging investigations 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. Method: Fibre density (FD), fibre cross-section (FC), and the combined measure (FDC) within 72 WM tracts were compared among 33 individuals with BD-II, 50 with UD, and 51 healthy controls (HC). The effects of illness characteristics on FBA correlates were also examined. Sensitivity analyses compared these measures among unmedicated participants to check whether medication status affects the results. Results: Participants with BD-II and UD showed reduced FD in the left parieto-occipito-pontine (POPT) and striato-occipital (ST-OCC) tracts. Compared to UD, BD-II was associated with lower FD in the left arcuate fascicle (AF) and bilateral superior longitudinal fasciculi I and II (SLF-I and II). In BD-II, illness duration negatively correlated with FD in left AF, left POPT, and right ST-OCC, while the number of lifetime BD-II depressive episodes positively correlated with FDC in left SLF-I. Group differences were significant but less pronounced in unmedicated participants. Conclusions: Our findings demonstrate shared and distinct WM abnormalities in tracts involved in visuomotor and executive processes in BD-II and UD, with BD-II exhibiting more extensive alterations. With BD-II, but not UD, longer illness duration was linked to lower FD, while depression recurrence was associated with higher FDC, suggesting potential degenerative and compensatory neurobiological mechanisms. Longitudinal studies should investigate the joint trajectories of symptomatology and WM alterations.