White Matter Changes During Manic and Depressive Episodes and Phase Switching in Bipolar Disorder: A Tractography Study

INTRODUCTION: Bipolar disorder (BD) is a severe psychiatric condition characterized by recurrent episodes of mania and depression. A critical aspect of BD is phase switching, the rapid transition between affective states, which remains poorly understood at the neurobiological level. Recent neuroimaging advancements, particularly in diffusion tensor imaging (DTI) and tractography, have provided insights into the structural white matter (WM) alterations associated with mood transitions. METHODS: We conducted an integrated diffusion neuroimaging study to investigate WM modifications in BD patients experiencing manic and depressive phases, as well as those undergoing phase switching. Thirty-two BD type I patients (14 manic, 18 depressive) and 20 healthy controls underwent Magnetic Resonance Imaging scanning, including DTI-based analyses. WM integrity was assessed using Tract-Based Spatial Statistics (TBSS) and tractography to explore fractional anisotropy (FA) differences. RESULTS: Compared to healthy controls and depressive BD patients, manic BD patients exhibited significant FA reductions in the corpus callosum, anterior limb of the internal capsule, and thalamic projections. Tractography revealed local FA alterations in fronto-limbic and occipito-parietal pathways, suggesting disrupted structural connectivity. Phase switching was associated with reduced FA in the right superior longitudinal fasciculus III, indicating its potential role as a neurobiomarker of mood instability. CONCLUSION: Our findings highlight widespread WM abnormalities in BD, particularly in manic phases, and suggest a neurobiological signature for phase switching. Understanding these alterations can improve early detection, targeted interventions, and personalized treatment approaches for BD.