Direct and Indirect Associations of Widespread Individual Differences in Brain White Matter Microstructure With Executive Functioning and General and Specific Dimensions of Psychopathology in Children

Carlos Cardenas-Iniguez, Tyler M. Moore, Antonia N. Kaczkurkin, Francisco A.C. Meyer, Theodore D. Satterthwaite, Damien A. Fair, Tonya White, Elisabet Blok, Brooks Applegate, Lauren M. Thompson, Monica D. Rosenberg, Donald Hedeker, Marc G. Berman, Benjamin B. Lahey

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Executive functions (EFs) are important partly because they are associated with risk for psychopathology and substance use problems. Because EFs have been linked to white matter microstructure, we tested the prediction that fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts are associated with EFs and dimensions of psychopathology in children younger than the age of widespread psychoactive substance use. Methods: Parent symptom ratings, EF test scores, and diffusion tensor parameters from 8588 9- to 10-year-olds in the ABCD Study (Adolescent Brain Cognitive Development Study) were used. Results: A latent factor derived from EF test scores was significantly associated with specific conduct problems and attention-deficit/hyperactivity disorder problems, with dimensions defined in a bifactor model. Furthermore, EFs were associated with FA and MD in 16 of 17 bilateral white matter tracts (range: β =. 05; SE =. 17; through β = −.31; SE =. 06). Neither FA nor MD was directly associated with psychopathology, but there were significant indirect associations via EFs of both FA (range: β =. 01; SE =. 01; through β = −.09; SE =. 02) and MD (range: β =. 01; SE =. 01; through β =. 09; SE =. 02) with both specific conduct problems and attention-deficit/hyperactivity disorder in all tracts except the forceps minor. Conclusions: EFs in children are inversely associated with diffusion tensor imaging measures in nearly all tracts throughout the brain. Furthermore, variance in diffusion tensor measures that is shared with EFs is indirectly shared with attention-deficit/hyperactivity disorder and conduct problems.

Original languageEnglish (US)
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute of Drug Abuse (Grant No. UG3-DA045251 ) , the National Institute of Mental Health (Grant Nos. R01-MH098098 , R01-MH117014 , and R01-MH117274 ), the National Institutes of Health (Grant Nos. UL1-TR000430 and UL1-TR000445 ), the Brain and Behavior Research Foundation (NARSAD Young Investigator Award), and the Lifespan Brain Institute of the University of Pennsylvania and the Children's Hospital of Philadelphia. Research reported in this publication also benefited from the ABCD Workshop on Brain Development and Mental Health, supported by the National Institute of Mental (Grant No. R25MH120869 ).

Funding Information:
Data used in the preparation of this article were obtained from the ABCD Study ( https://abcdstudy.org ), held in the National Institute of Mental Health Data Archive. This is a multisite, longitudinal study designed to recruit >10,000 children 9 to 10 years of age and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners (Grant Nos. U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, and U01DA041025). A full list of ABCD Study supporters is available at https://abcdstudy.org/nih-collaborators . A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html . ABCD Consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report.

Funding Information:
This work was supported by the National Institute of Drug Abuse (Grant No. UG3-DA045251), the National Institute of Mental Health (Grant Nos. R01-MH098098, R01-MH117014, and R01-MH117274), the National Institutes of Health (Grant Nos. UL1-TR000430 and UL1-TR000445), the Brain and Behavior Research Foundation (NARSAD Young Investigator Award), and the Lifespan Brain Institute of the University of Pennsylvania and the Children's Hospital of Philadelphia. Research reported in this publication also benefited from the ABCD Workshop on Brain Development and Mental Health, supported by the National Institute of Mental (Grant No. R25MH120869). Data used in the preparation of this article were obtained from the ABCD Study (https://abcdstudy.org), held in the National Institute of Mental Health Data Archive. This is a multisite, longitudinal study designed to recruit >10,000 children 9 to 10 years of age and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners (Grant Nos. U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, and U01DA041025). A full list of ABCD Study supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD Consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD Consortium investigators. We appreciate the extremely helpful comments of David Cole on the interpretation of the tests of indirect association. The ABCD Study data used in this study can be accessed at https://nda.nih.gov/abcd. The ABCD data repository grows and changes over time. The ABCD data used in this report came from RRID:SCR_015769, doi: 1.15154/1503209. The preprocessing and analysis code are available on GitHub. The data used for all these analyses is available for download from the National Institute of Mental Health Data Archive (nda.nih.gov) under Study 945 (doi: 1.15154/1519200). The authors report no biomedical financial interests or potential conflicts of interest.

Publisher Copyright:
© 2020 Society of Biological Psychiatry

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Attention-deficit/hyperactivity disorder
  • Bifactor models
  • Conduct problems
  • Executive functions
  • General factor of psychopathology
  • White matter

PubMed: MeSH publication types

  • Journal Article

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