Extending the ‘cross-disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

• Type of Material: Article
• Authors: Lauren M. McGrath, American University; Ellen B. Braaten, Massachusetts General Hospital; Nathan D. Doty, Massachusetts General Hospital; Brian L. Willoughby, Massachusetts General Hospital; H. Kent Wilson, Massachusetts General Hospital; Ellen H. O'Donnell, Massachusetts General Hospital; Mary K. Colvin, Massachusetts General Hospital; Hillary L. Ditmars, Massachusetts General Hospital; Jessica E. Blais, Massachusetts General Hospital; Erin N. Hill, Massachusetts General Hospital; Aaron Metzger, West Virginia University; Roy H. Perlis, Massachusetts General Hospital; Erik G. Willcutt, University of Colorado; Jordan W. Smoller, Massachusetts General Hospital; Irwin Waldman, Emory University; Stephen V. Faraone, SUNY Upstate Medical University; Larry J. Seidman, Massachusetts General Hospital; Alysa E. Doyle, Massachusetts General Hospital
• Language: English
• Date: 2015-09-28
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Association for Child and Adolescent Mental Health
• Final Published Version (URL): http://dx.doi.org/10.1111/jcpp.12463
• Title of Journal or Parent Work: Journal of Child Psychology and Psychiatry
• ISSN: 0021-9630
• Volume: 57
• Issue: 4
• Start Page: 462
• End Page: 471
• Grant/Funding Information: The author receives royalties from UBC, a Medco subsidiary.; The author receives support from NIMH, the Massachusetts Department of Mental Health, and the Sidney R. Baer, Jr. Foundation.; In the past year, author S.F. received consulting income, travel expenses and/or research support from Akili Interactive Labs, Alcobra, VAYA Pharma, and SynapDx and research support from the National Institutes of Health (NIH).; This research was supported in part by the Stanley Center for Psychiatric Research and R03 MH106862 (to A.E.D.), an American University faculty research support grant (to L.M.M.), and the David Judah Foundation (to A.E.D. and E.B.B.).; The author receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health and Oxford University Press: Schizophrenia: The Facts.
• Keywords: dimensional traits; social responsiveness; psychosis; executive functions; cross-disorder; mania
• Research Categories: Biology, Genetics; Psychology, Clinical; Psychology, General

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 to 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 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 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, relate 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.