Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders

•Amygdala FxC in response to emotion processing is abnormal in youth with BPSD.•Amygdala-VLPFC FxC to all emotions is positive in BPSD but inverse in HC and ADHD.•Amygdala-subgenual FxC to negative emotions is positive in BPSD but inverse in HC.•VLPFC findings are specific to BPSD, and not found in youth with ADHD.•Subgenual FxC also varies with depression and stimulant medication.

ObjectiveBoth bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task.MethodsWe scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex.ResultsFxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions