title: Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.
abstract: Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP.
  
  
  
  Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed.
  
  
  
  Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group⁎sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only.
  
  
  
  Cross-sectional design and small sample size.
  
  
  
  Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration.
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Adriane M
authors.initials: AM
authors.lastname: Soehner
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Manelis
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Cecile D
authors.initials: CD
authors.lastname: Ladouceur
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Graur
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Monk
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Bonar
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hickey
authors.affiliation: Department of Psychiatry, Nationwide Children's Hospital and the Ohio State College of Medicine, Columbus, OH, USA.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences University of Toronto, Faculty of Medicine, Toronto, ON, CA.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Tina R
authors.initials: TR
authors.lastname: Goldstein
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000339:Affect / Q000502:physiology*; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology*; D063132:Connectome; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019964:Mood Disorders / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology*; D012201:Reward; D012890:Sleep / Q000502:physiology*
keywords: Bipolar disorder risk; Functional MRI; Reward processing; Sleep