Previous neuroimaging studies of youth with bipolar disorder(BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n=59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes. Whole brain analysis was used to identify clusters that showed differential activation to emotion vs. shapes across group. To assess pair-wise comparisons and potential confounders, mean activation data were extracted only from clusters within regions previously implicated in emotion regulation (including amygdala and ventral prefrontal regions). A cluster in the right inferior frontal gyrus (IFG) showed group differences to emotion vs. shapes (159 voxels, corrected p<.05). Within this cluster, U-BD youth showed decreased activation relative to HC (p=.007) and non-BD (p=.004) youth. M-BD also showed decreased activation in this cluster relative to HC and non-BD youth, but these differences were attenuated. Results were specific to negative emotions, and not found with happy faces. IFG findings were not explained by other medications (e.g. stimulants) or diagnoses. Compared to both HC and a non-BD sample, U-BD is associated with abnormally decreased right IFG activation to negative emotions
