Lower orbital frontal white matter integrity in adolescents with bipolar I disorder.

OBJECTIVE To examine white matter microstructure, as assessed via diffusion tensor imaging (DTI), in adolescents with bipolar I disorder compared with control volunteers. METHOD Twenty-six (12 male and 14 female subjects) adolescents (mean age, 16.0 years) with bipolar I disorder and 26 (14 male and 12 female subjects) control volunteers (mean age, 15.3 years) completed structural and DTI examinations. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were compared between groups in the brain white matter using a voxelwise analysis after intersubject registration to Talairach space. Exploratory analyses were performed to assess structure-function correlations in a subgroup of 11 patients with available neuropsychological measures. RESULTS Compared with the control volunteers, the patients demonstrated abnormalities in white matter regions predicted to differ a priori between groups, including lower FA in the right orbital frontal lobe and higher ADC in the right and left subgenual region (p <.005, uncorrected; cluster size >or= 100). There were no areas of higher FA or lower ADC in patients compared with control volunteers. Lower FA across regions that differed significantly between groups correlated significantly with slower visuomotor speed among patients with bipolar disorder. CONCLUSIONS Abnormalities involving the orbital frontal and subgenual white matter in adolescents with bipolar disorder are consistent with neurobiological models that implicate dysregulation of affective systems and impulsivity in the pathophysiology of the disorder. Preliminary findings suggest that white matter abnormalities in pediatric bipolar disorder have functional correlates and may be useful in constructing neurobiological models of the disorder.