Regional microstructural changes of the corpus callosum in bipolar disorder: A diffusion MRI tractography study with an exploratory brain-age analysis.

Bipolar disorder (BD) is associated with white matter dysconnectivity; however, the regional specificity of changes in the corpus callosum (CC) and their relationship with accelerated aging remain unclear. Using deterministic tractography, we investigated CC microstructure and, as a secondary exploratory aim, age-related changes in the CC. Fifty-seven participants (32 with BD, 25 controls) underwent diffusion MRI. Tractography analysis was applied to the subregions of the CC (forceps minor, corpus callosum body, forceps major, and tapetum) and the anterior commissure. Group differences were assessed using ANCOVA, controlling for age and sex. Exploratory Elastic Net regression was used to model normative brain age in the control group. BD patients exhibited lower fractional anisotropy and higher diffusivity across CC regions. The significant increase in radial diffusivity in the forceps major remained significant after false discovery rate correction (FDR p = 0.026, partial η² = 0.16); however, this effect was attenuated and no longer significant after excluding seven influential observations (n = 50; adjusted difference +0.042, 95% CI 0.006-0.079; unadjusted p = 0.023; FDR p = 0.20). Brain age analyses showed no signs of accelerated aging in the corpus callosum. These findings suggest localized microstructural deterioration in the posterior callosal fibers rather than widespread commissural degeneration.