Impact of Bipolar Disorder Increased White Matter Hyperintensities on White Matter Connectivity

Individuals with bipolar disorder have been reported to have increased white matter hyperintensities (WMH) in fluid-attenuated inversion recovery (FLAIR) magnetic resonance scans. However, it is unknown whether this WMH increase has any impact on white matter connectivity. The present study aimed to evaluate the effects of the bipolar disorder-related WMH increase on white matter tracts and networks.

An expert neuroradiologist blindly assessed the type, size, and location of WMH from 128 FLAIR scans (bipolar disorder: n = 64, age = 38 ± 7 years; 53% females; matched healthy controls: n = 64, age = 36 ± 10 years, 58% females). Afterward, we conducted an atlas-based analysis comparing the mean percentage parcel of damage in the white matter tracts of the Human Connectome Project tractography template and the networks of the 7-Network Cortical Parcellation template.

We did not detect WMH-related effects on white matter connectivity when correcting for multiple comparisons. However, at the uncorrected level, we found a higher WMH-related white matter disconnection in the right inferior fronto-occipital fasciculus and the right middle longitudinal fasciculus.

This study evaluates, for the first time, the impact of WMH on bipolar brain structural connectivity. It finds an effect on two fasciculi, providing hints into one potential origin of the brain networks' alterations reported in the disorder. However, we only observed these results at the uncorrected statistical level, for which they are likely small and should be taken with caution until replicated.