title: Parsing dimensional vs diagnostic category-related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the Longitudinal Assessment of Manic Symptoms study.
abstract: OBJECTIVE
  Pediatric disorders characterized by behavioral and emotional dysregulation pose diagnostic and treatment challenges because of high comorbidity, suggesting that they may be better conceptualized dimensionally rather than categorically. Identifying neuroimaging measures associated with behavioral and emotional dysregulation in youth may inform understanding of underlying dimensional vs disorder-specific pathophysiologic features.
  
  
  OBJECTIVE
  To identify, in a large cohort of behaviorally and emotionally dysregulated youth, neuroimaging measures that (1) are associated with behavioral and emotional dysregulation pathologic dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder, anxiety, and disruptive behavior disorders).
  
  
  METHODS
  A multisite neuroimaging study was conducted from February 1, 2011, to April 15, 2012, at 3 academic medical centers: University Hospitals Case Medical Center, Cincinnati Children's Hospital Medical Center, and University of Pittsburgh Medical Center. Participants included a referred sample of behaviorally and emotionally dysregulated youth from the Longitudinal Assessment of Manic Symptoms (LAMS) study (n = 85) and healthy youth (n = 20).
  
  
  METHODS
  Region-of-interest analyses examined relationships among prefrontal-ventral striatal reward circuitry during a reward paradigm (win, loss, and control conditions), symptom dimensions, and diagnostic categories.
  
  
  RESULTS
  Regardless of diagnosis, higher PGBI-10M scores were associated with greater left middle prefrontal cortical activity (r = 0.28) and anxiety with greater right dorsal anterior cingulate cortical (r = 0.27) activity to win. The 20 highest (t = 2.75) and 20 lowest (t = 2.42) PGBI-10M-scoring youth showed significantly greater left middle prefrontal cortical activity to win compared with 20 healthy youth. Disruptive behavior disorders were associated with lower left ventrolateral prefrontal cortex activity to win (t = 2.68) (all P < .05, corrected).
  
  
  CONCLUSIONS
  Greater PGBI-10M-related left middle prefrontal cortical activity and anxiety-related right dorsal anterior cingulate cortical activity to win may reflect heightened reward sensitivity and greater attention to reward in behaviorally and emotionally dysregulated youth regardless of diagnosis. Reduced left ventrolateral prefrontal cortex activity to win may reflect reward insensitivity in youth with disruptive behavior disorders. Despite a distinct reward-related neurophysiologic feature in disruptive behavior disorders, findings generally support a dimensional approach to studying neural mechanisms in behaviorally and emotionally dysregulated youth.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Fournier
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Hinze
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Perlman
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Claudiu
authors.initials: C
authors.lastname: Schirda
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Travis
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: Division of Child and Adolescent Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio.
authors.forename: Christine
authors.initials: C
authors.lastname: Demeter
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, Michigan.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Gary
authors.initials: G
authors.lastname: Ciuffetelli
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Eric
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Thomas
authors.initials: T
authors.lastname: Olino
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Erika
authors.initials: E
authors.lastname: Forbes
authors.affiliation: Division of Child and Adolescent Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Sunshine
authors.affiliation: Division of Pediatric Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Holland
authors.affiliation: Research Institute, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kowatch
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Department of Child Psychiatry, School of Medicine, New York University, New York.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Department of Psychiatry, The Ohio State University, Columbus.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, The Ohio State University, Columbus.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Fristad
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.affiliation: Division of Child and Adolescent Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio9Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania10Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000503:physiopathology*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000503:physiopathology; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000502:physiology / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002653:Child Behavior Disorders / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000502:physiology / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D012201:Reward