Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder

Abstract

ObjectivesAffective dysregulation is a core feature of bipolar disorder (BD). Abnormalities in neural circuits underlying affect regulation have been observed in BD, specifically in the structure and function of the amygdala and orbital frontal cortex (OFC). Fear extinction is an automatic affect regulatory process relying on neural circuits that are abnormal in BD. Thus, fear extinction might be useful in probing automatic affect regulation deficits in BD. We tested the hypothesis that BD is associated with reduced ability to extinguish fear responses. MethodsWe examined fear conditioning, extinction, and extinction memory recall in a sample of stable, euthymic participants with BD (n=19) vs. healthy comparison participants (n=32). A limited number of subjects (BD: n=12; healthy comparison: n=11) underwent structural MRI scanning to examine cortical size associations with extinction recall. ResultsBoth healthy comparison and BD participants were successful in acquiring a fear response, but BD participants responded with greater startle to both threat and safety cues. Both groups showed significant extinction. The BD group showed superior extinction recall. Extinction recall was associated with right rostral middle frontal cortex thickness across groups, whereas right OFC surface area was associated with recall only in healthy comparisons. LimitationsLimitations include use of a stable, highly screened sample and a relatively small number of participants available for MRI analysis. ConclusionsIncreased fear reactivity may be related to a “trait” disruption in BD patients similar to that previously described in anxiety disorders. This task may be useful for probing automatic affect regulatory processes in BD, and understanding treatment response.