Whole-Brain White Matter Alterations in Bipolar Disorder: A Systematic Review and Meta-Analysis of TBSS and Voxel-Based DTI Studies

Bipolar disorder (BD) has been associated with alterations in white matter microstructure, but the spatial consistency of these findings across diffusion tensor imaging (DTI) studies remains uncertain. This project aims to systematically review and quantitatively synthesize whole-brain DTI findings comparing individuals with bipolar disorder and healthy controls. Studies employing tract-based spatial statistics (TBSS) and voxel-based analysis (VBA) will be identified through systematic searches of PubMed, Embase, Web of Science, PsycINFO, and Scopus. Fractional anisotropy (FA) will serve as the primary diffusion metric, while mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) will be examined as secondary outcomes. Where sufficient independent data are available, coordinate-based meta-analyses will be conducted using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), with TBSS and VBA studies analyzed separately. The study aims to identify spatially consistent white matter abnormalities associated with bipolar disorder and evaluate the robustness of the available neuroimaging evidence.