title: Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication.
abstract: 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.
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA. Electronic address: hafemand@upmc.edu.
authors.forename: Danella M
authors.initials: DM
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: 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, 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, Ohio State University, USA.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Psychiatry, 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: Janssen Pharmaceuticals Research & Development of Johnson & Johnson, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Drevets
authors.affiliation: Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, USA; Psychological Medicine, Cardiff University, UK.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000098:blood supply / Q000503:physiopathology; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D005145:Face; D005149:Facial Expression; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual; D010775:Photic Stimulation
chemical_list: D014150:Antipsychotic Agents; D010100:Oxygen
keywords: Bipolar disorder; Emotion regulation; Functional MRI (fMRI); Neuroimaging; Psychopharmacology