title: Decreased amygdala-insula resting state connectivity in behaviorally and emotionally dysregulated youth.
abstract: The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America. Electronic address: bebkog@upmc.edu.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Michele
authors.initials: M
authors.lastname: Bertocci
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Henry
authors.initials: H
authors.lastname: Chase
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Dwojak
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Almeida
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Susan Beth
authors.initials: SB
authors.lastname: Perlman
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Claudiu
authors.initials: C
authors.lastname: Schirda
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Travis
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Demeter
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, United States of America.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Diwadkar
authors.affiliation: University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sunshine
authors.affiliation: Cincinnati Children׳s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Holland
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, OH, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Kowatch
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, OH, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Horwitz
authors.affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, OH, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frazier
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, OH, United States of America.
authors.forename: Lawrence Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, OH, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Fristad
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Youngstrom
authors.affiliation: University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, United States of America; Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Findling
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
authors.forename: Mary Louise
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000503:physiopathology*; D001007:Anxiety / Q000503:physiopathology; D001008:Anxiety Disorders / Q000503:physiopathology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000503:physiopathology; D001714:Bipolar Disorder / Q000503:physiopathology*; D016022:Case-Control Studies; D003863:Depression / Q000503:physiopathology; D003866:Depressive Disorder / Q000503:physiopathology; D004644:Emotions / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010555:Personality Inventory; D055815:Young Adult
keywords: Adolescents; Amygdala; Insula; RDoC; fMRI