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Altered White Matter Tracts in Bipolar Disorder: Insights from DTI Analysis

Mostafavi, A.; Mohammadizadeh, H.; Younesi, G.; Rahmani, E.

2025-06-03 psychiatry and clinical psychology
10.1101/2025.06.03.25328854 medRxiv
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IntroductionBipolar Disorder (BD) is characterized by marked disruptions in emotional regulation and cognitive control, often accompanied by structural abnormalities in the brains white matter. Diffusion tensor imaging (DTI) offers a window into white matter microstructure through metrics such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). This study aimed to examine white matter tract alterations in individuals with BD compared to healthy controls (HCs) and to explore potential associations between DTI metrics and clinical symptom severity. MethodsWe conducted a voxel-wise whole-brain DTI analysis in a sample of BD patients and age-matched HCs, focusing on FA, MD, RD, and AD values. Group comparisons were performed to identify significant differences in white matter integrity. In addition, we assessed correlations between DTI metrics and psychological assessment scores to investigate links between structural alterations and clinical features. ResultsCompared to HCs, BD patients exhibited significantly lower FA in several major white matter tracts, including the cingulum (olfactory tract), forceps minor of the corpus callosum, fornix, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. These reductions suggest disrupted microstructural coherence. In parallel, elevated MD, RD, and AD in overlapping regions point to possible myelin degeneration or axonal injury. However, associations between DTI metrics and psychological symptom scores were weak and did not reach statistical significance. Discussion/ConclusionThese findings reinforce the presence of widespread white matter abnormalities in BD, particularly in tracts relevant to emotional and cognitive processing. While structural disruptions were evident, their weak correlations with symptom severity highlight the complex relationship between brain microstructure and clinical expression in BD. Future studies are warranted to clarify the diagnostic and prognostic relevance of DTI-based biomarkers in mood disorders.

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