title: Reward-related neural activity and structure predict future substance use in dysregulated youth.
abstract: BACKGROUND
  Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.
  
  
  METHODS
  LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.
  
  
  RESULTS
  Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.
  
  
  CONCLUSIONS
  These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.
authors.affiliation: Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: M 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, PA,USA.
authors.forename: G
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, PA,USA.
authors.forename: A
authors.initials: A
authors.lastname: Versace
authors.affiliation: Department of Statistics,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: S
authors.initials: S
authors.lastname: Iyengar
authors.affiliation: Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: L
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, PA,USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Forbes
authors.affiliation: Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: J R C
authors.initials: JRC
authors.lastname: Almeida
authors.affiliation: Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: S 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, PA,USA.
authors.forename: C
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, PA,USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Travis
authors.affiliation: Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Gill
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience,Wayne State University,Detroit, MI,USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Diwadkar
authors.affiliation: Department of Radiology,University Hospitals Case Medical Center/Case Western Reserve University,Cleveland, OH,USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Sunshine
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati,Cincinnati, OH,USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Holland
authors.affiliation: Department of Psychiatry and Behavioral Health,Ohio State University,Columbus, OH,USA.
authors.forename: R 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, PA,USA.
authors.forename: B
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry and Behavioral Health,Ohio State University,Columbus, OH,USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Axelson
authors.affiliation: Pediatric Institute,Cleveland Clinic,Cleveland, OH,USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Frazier
authors.affiliation: Department of Psychiatry and Behavioral Health,Ohio State University,Columbus, OH,USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry and Behavioral Health,Ohio State University,Columbus, OH,USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Fristad
authors.affiliation: Department of Psychology,University of North Carolina at Chapel Hill,Chapel Hill, NC,USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Youngstrom
authors.affiliation: Department of Child and Adolescent Psychiatry,New York University School of Medicine,New York, NY,USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Department of Psychiatry,Johns Hopkins University,Baltimore, MD,USA.
authors.forename: R 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, PA,USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology*; D000342:Affective Symptoms / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology; D002648:Child; D003863:Depression / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D000066553:Problem Behavior; D012201:Reward; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology
keywords: Functional magnetic resonance imaging; GLMNET; LASSO; substance use; youth