OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions that bipolar disorder is characterized by subtle white matter changes. The chronic nature of the study population, however, has limited interpretation of these findings. In this study the authors utilized diffusion tensor imaging to study white matter tracts of adolescents in their first episode of mania to address whether abnormalities are present in early bipolar disorder. METHOD: Eleven medication-naive adolescents in their first episode of mania and 17 healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy and trace apparent diffusion coefficients of prefrontal and posterior regions of interest were compared between groups. RESULTS: Bipolar adolescents showed significantly decreased fractional anisotropy only in superior-frontal white matter tracts. Trace apparent diffusion coefficients did not significantly differ in any regions examined. CONCLUSIONS: These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.