Identifying alterations in white matter (WM) circuitry in bipolar disorder (BD) may offer crucial insights into the neurobiology of the illness and support biomarker discovery for interventional and genetic studies. Although prior diffusion MRI (dMRI) studies have reported WM abnormalities in BD, few have used fine-scale spatial mapping along tracts (tractometry), and most rely solely on fractional anisotropy (FA), overlooking complementary dMRI metrics related to other microstructural properties. Large-scale multisite tractometry studies remain scarce, limiting power to detect subtle effects and generalizability. Here, we applied BUndle ANalytics (BUAN) to conduct along-tract tractometry of FA, and axial, radial, and mean diffusivity (AD, RD, MD) across 37 major WM tracts in 148 individuals with BD (mean age=36.8 ± 13.5 years; 48% female) and 258 healthy (37.9 ± 13.7 years; 58% female) controls from 6 international sites from the ENIGMA Bipolar Disorder Working Group. Larger samples led to better detection of group-level effects, supporting the benefits of large-scale data harmonization. We identified spatially localized WM microstructural differences in BD across visual, limbic, interhemispheric, language, and sensorimotor pathways including the optic radiation, uncinate and arcuate fasciculi, forceps major of the corpus callosum, extreme capsule, and brainstem tracts. In the largest study to date, our findings demonstrate the value of large-scale, multidimensional tractometry for mapping WM alterations along brain circuits in psychiatric illness.
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Nabulsi et al. (2025) studied this question.