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

Danella Hafeman, Genna Bebko, Michele A. Bertocci, Jay C. Fournier, Henry W. Chase, Lisa Bonar, Susan B. Perlman, Michael Travis, Mary Kay Gill, Vaibhav A. Diwadkar, Jeffrey L. Sunshine, Scott K. Holland, Robert A. Kowatch, Boris Birmaher, David Axelson, Sarah M. Horwitz, L. Eugene Arnold, Mary A. Fristad, Thomas W. Frazier, Eric A. YoungstromRobert L. Findling, Mary L. Phillips

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Objective Both 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. Methods We 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. Results FxC 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<shapes). A group x emotion interaction was found in amygdala-subgenual cingulate FxC (p=.025), explained by differences in FxC in response to negative emotions. While BPSD showed positive FxC, HC showed inverse FxC; ADHD were intermediate. Amygdala-subgenual FxC was also positively associated with depressive symptoms and stimulant medication. Limitations Co-morbidity and relatively small sample size. Conclusions Youth with BPSD showed abnormally positive FxC between amygdala and regions in the ventral prefrontal cortex during emotion processing. In particular, the amygdala-VLPFC finding was specific to BPSD, and not influenced by other diagnoses or medications.

Original languageEnglish (US)
Pages (from-to)94-100
Number of pages7
JournalJournal of Affective Disorders
StatePublished - Jan 15 2017


  • Bipolar disorder
  • Implicit emotion processing
  • Neuroimaging
  • fMRI

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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