State dependent cortico-amygdala circuit dysfunction in bipolar disorder

Background: Existing models of the pathophysiology of bipolar disorder posit disruption in neural circuits of emotion regulation and reward processing. However, few fMRI studies have compared regional brain activity and connectivity in different mood states in bipolar disorder to determine if manic symptomatology is reflected in specific circuit abnormalities. The purpose of this study was to test the hypothesis that bipolar mania is associated with altered connectivity between cortical regions thought to regulate subcortical structures such as the amygdala and striatum.

Methods: 28 subjects with bipolar disorder in a manic state, 24 different bipolar subjects in a euthymic state, and 23 matched healthy comparison subjects underwent resting state fMRI scans. Several cortical and sub-cortical structures implicated in the pathogenesis of bipolar disorder were selected for study. We conducted a whole-brain analysis of functional connectivity of these regions.

Results: Bipolar mania was differentiated from euthymia by decreased functional connectivity between the amygdala and anterior cingulate cortex (ACC). Mania was also characterized by increased connectivity between amygdala and dorsal frontal cortical structures that are normally anti-correlated in emotion regulation tasks.

Limitations: Both groups of bipolar subjects were prescribed medications. The study was not longitudinal in design.

Conclusions: Compared to bipolar subjects in a euthymic state, subjects in the manic state demonstrate disrupted functional connectivity between brain regions involved in the regulation of emotion and the amygdala. This disruption of activity in neural circuits involved in emotion may underlie the emotional dysregulation inherent to a bipolar manic episode.