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Author Notes:

Correspondence. Alysa E. Doyle, MGH Center for Human Genetic Research, 185 Cambridge Street, Simches 6240, Boston, MA 02114, USA; doylea@helix.mgh.harvard.edu

The authors wish to thank Pieter Vuijk for his comments on this manuscript. Author R.P. consults to or serves on scientific advisory boards for Genomind, Healthrageous, Pamlab, Perfect Health, Pfizer, Proteus Biomedical, Psybrain, and RIDVentures.

The author’s institution is seeking a patent for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD.

Author J.S. serves on the scientific advisory board of PsyBrain.

Dr. Seidman reports no competing interests.

All other authors declare that they have no competing or potential conflicts of interests.

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Research Funding:

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 UBC, a Medco subsidiary.

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).

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.

The author receives support from NIMH, the Massachusetts Department of Mental Health, and the Sidney R. Baer, Jr. Foundation.

Keywords:

  • executive functions
  • mania
  • psychosis
  • social responsiveness
  • cross-disorder
  • dimensional traits

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

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Journal Title:

Journal of Child Psychology and Psychiatry

Volume:

Volume 57, Number 4

Publisher:

, Pages 462-471

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2015 Association for Child and Adolescent Mental Health

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