title: Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Co-morbidity and relatively small sample size.
  
  
  
  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.
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Danella
authors.initials: D
authors.lastname: Hafeman
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Fournier
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Henry W
authors.initials: HW
authors.lastname: Chase
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonar
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Perlman
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Travis
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: Psychiatry and Behavioral Neuroscience, Wayne State University, USA.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
authors.affiliation: University Hospitals Case Medical Center/Case Western Reserve University, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Sunshine
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, USA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Holland
authors.affiliation: The Research Institute at Nationwide Children's Hospital, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kowatch
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Psychiatry and Behavioral Health, Ohio State University, USA.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Child Psychiatry, New York University School of Medicine, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Psychiatry and Behavioral Health, Ohio State University, USA.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Psychiatry and Behavioral Health, Ohio State University, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Fristad
authors.affiliation: Cleveland Clinic, Center for Pediatric Behavioral Health, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Frazier
authors.affiliation: Psychology, University of North Carolina at Chapel Hill, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.affiliation: University Hospitals Case Medical Center/Case Western Reserve University, USA; Psychiatry, Johns Hopkins University, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA; Psychological Medicine, Cardiff University, United Kingdom.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000503:physiopathology; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D003937:Diagnosis, Differential; D004644:Emotions / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011603:Psychophysiology
keywords: Bipolar disorder; Implicit emotion processing; Neuroimaging; fMRI