BACKGROUND:Recent reports in the literature document an association between focal white matter abnormalities in bipolar as well as unipolar mood disorder. The importance of this finding and other associated anatomic differences is uncertain. METHODS:We examined the volume of abnormal white matter and other brain volumes using quantitative magnetic resonance imaging analysis. We explored the relationship of these variables with diagnosis, cognitive function, and clinical variables in 36 patients with bipolar disorder, 30 patients with unipolar disorder, and 26 control subjects who were free from significant medical and neurologic illness. RESULTS:Younger patients with bipolar disorder (but not similarly aged patients with unipolar disorder or controls) have an increased volume of abnormal white matter. Data also indicate that the total volume of abnormal white matter may be associated with increased cognitive impairment, increased rate of psychiatric illness in the family, and onset after adolescence. CONCLUSION:Patients with bipolar disorder demonstrate a pattern of subcortical brain morphologic abnormalities and cognitive impairment.