Progressive gray matter loss in patients with bipolar disorder

Background: Structural brain abnormalities of the medial temporal lobe have been found in people with bipolar disorder (BPD). It is not known whether these abnormalities progress over the course of the illness or how they relate to neurcipsychologic functioning. We sought to address these uncertainties in a prospective cohort study of people with bipolar I disorder. Methods: Twenty patients with bipolar I disorder and 21 control subjects were recruited from the community. Participants were group matched for age, sex, and premorbid IQ. Longitudinal change in gray matter density was assessed using magnetic resonance imaging and evaluated using the technique of tensor-based morphometry with SPM2 software. Changes in gray and white matter density were estimated and compared with changes in cognitive function and clinical outcome. Results: Patients with BPD showed a larger decline in hippocampal, fusiform, and cerebellar gray matter density over 4 years than control subjects. No significant changes in white matter density were found. Reductions in temporal lobe gray matter correlated with decline in intellectual function and with the number of intervening mood episodes over the follow-up period. Conclusions: Patients with BPD lose hippocampal, fusiform and cerebellar gray matter at an accelerated rate compared with healthy control subjects. This tissue loss is associated with deterioration in cognitive function and illness course.