White matter alterations in the corpus callosum and visual cortical regions associated with depressive and psychotic symptoms in early‐onset bipolar disorder

AIM: White matter (WM) alterations in the corpus callosum (CC) and visual cortex have been implicated in early psychosis, with the visual regions particularly linked to psychotic symptoms. Whether similar WM patterns occur in early-onset bipolar disorder (EOBD) remains unclear. This study investigated WM alterations in EOBD and their associations with psychiatric symptoms. METHODS: Eighty-seven individuals with EOBD and 57 healthy controls (HCs) underwent diffusion magnetic resonance imaging (dMRI) and psychiatric assessments. Whole-brain WM changes between groups were examined using TractSeg and tract-based spatial statistics. Partial correlations with multiple comparison corrections assessed associations between altered tracts and symptoms. RESULTS: Compared with HCs, EOBD showed widespread lower fractional anisotropy (FA) and altered other WM parameters, particularly in the CC and visual-related tracts. Lower FA in the anterior midbody CC (r = -0.307, q = 0.038), right superior longitudinal fascicle I (r = -0.305, q = 0.038), thalamo-parietal (r = -0.315, q = 0.038), and parieto-occipital pontine tracts (r = -0.329, q = 0.038) correlated with greater depressive symptoms. Lower FA in the left inferior fronto-occipital fascicle (r = -0.371, q = 0.030), left optic radiation (r = -0.381, q = 0.030), and left thalamo-occipital tract (r = -0.392, q = 0.030) were associated with greater positive symptoms. These visual-related lower FAs were found more frequently in individuals with visual hallucinations. CONCLUSION: EOBD was associated with WM abnormalities in the CC and visual pathways linked to depressive symptoms and visual hallucinations, supporting its characterization as a neurodevelopmentally distinct subtype with persistent WM dysconnectivity.