White Matter Tract Alterations in Bipolar Disorder: A Systematic Review and Meta‐Analysis of Diffusion Tensor Imaging Studies

BACKGROUND: White matter microstructural changes have been frequently reported in bipolar disorder (BD), yet the magnitude and anatomical consistency of these alterations remain unclear across studies. METHODS: A systematic search of PubMed, Web of Science, and Scopus identified diffusion tensor imaging (DTI) studies comparing fractional anisotropy (FA) between individuals with BD and healthy controls. After screening, 145 studies were included in the systematic review. Of these, 28 studies provided tract-level FA data suitable for quantitative synthesis, yielding 78 independent region-specific effect-size entries, analyzed using random-effects models. Participant counts were deduplicated at the study level. RESULTS: Across the 145 studies included in the systematic review, there were 5372 participants with BD and 6240 healthy controls. Within the 28-study quantitative synthesis, pooled analyses suggested lower FA in BD across several white matter tracts, particularly those involved in fronto-limbic regulation and interhemispheric integration. Effect sizes and heterogeneity varied by tract, reflecting methodological, demographic, and clinical diversity among the quantitatively synthesized studies. CONCLUSIONS: These findings support the presence of region-specific white matter alterations in BD, particularly within tracts associated with emotional regulation, cognitive control, and hemispheric communication. While the results add anatomical detail to the existing evidence base, further harmonized, longitudinal, and multimodal studies are needed to examine clinical specificity, developmental timing, and biomarker potential.