Reduced Amygdala Volumes in First-Episode Bipolar Disorder and Correlation with Cerebral White Matter

Background: Previous magnetic resonance imaging (MRI) findings on amygdala volume abnormalities in bipolar disorder have been inconsistent, which may partly reflect clinical heterogeneity. It is unclear whether amygdala abnormalities are present early in the course of illness and/or are the consequence of disease progression. Methods: Twenty patients with first-episode bipolar disorder and 23 matched healthy comparison subjects were included. Magnetic resonance images were used to measure amygdala volumes, as well as whole brain measures of gray and white matter volume. Results: First-episode bipolar patients had significant reductions in amygdala volume relative to healthy subjects in an analysis of covariance that accounted for the effects of age, sex, and whole brain volume. First-episode patients also showed a trend reduction in cerebral white matter volume, and there was a significant correlation between cerebral white matter volume and total amygdala volume in patients but not control subjects. Conclusions: These findings indicate that amygdala volume deficits are present early in the course of bipolar disorder and may occur within a neuroanatomical context of reduced cerebral white matter. Additional research should examine whether the nature of regional white matter deficits, particularly in frontal-temporal tracts, may help parse the pathophysiology of amygdala volume abnormalities in bipolar disorder.