title: Extending the 'cross-disorder' relevance of executive functions to dimensional neuropsychiatric traits in youth.
abstract: BACKGROUND
  Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with 'cross-disorder' relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability.
  
  
  METHODS
  Data are from 393 participants, ages 8-17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of the autism spectrum disorder, bipolar illness, and schizophrenia (including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively).
  
  
  RESULTS
  We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits, but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting that it related to a general increase in psychopathology symptoms across those dimensions.
  
  
  CONCLUSIONS
  Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relates to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability.
authors.affiliation: School of Education, American University, Washington, DC, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: McGrath
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Braaten
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Doty
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Willoughby
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: H Kent
authors.initials: HK
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: O'Donnell
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Colvin
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Hillary L
authors.initials: HL
authors.lastname: Ditmars
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Blais
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Hill
authors.affiliation: Department of Psychology, West Virginia University, Morgantown, WV, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Metzger
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research at the Broad Institute of Harvard & MIT, Cambridge, MA, USA.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Willcutt
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research at the Broad Institute of Harvard & MIT, Cambridge, MA, USA.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.affiliation: Department of Psychology, Emory University, Atlanta, GA, USA.
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Waldman
authors.affiliation: Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Commonwealth Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research at the Broad Institute of Harvard & MIT, Cambridge, MA, USA.
authors.forename: Alysa E
authors.initials: AE
authors.lastname: Doyle
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000145:classification / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000145:classification / Q000503:physiopathology*; D002648:Child; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012559:Schizophrenia / Q000145:classification / Q000503:physiopathology*
keywords: Executive functions; cross-disorder; dimensional traits; mania; psychosis; social responsiveness