Abstract
Childhood is an important time for the manifestation of psychopathology. Psychopathology is characterized by considerable comorbidity which is mirrored in the underlying neural correlates of psychopathology. Both common and dissociable variations in brain volume have been found across multiple mental disorders in adult and youth samples. However, the majority of these studies used samples with broad age ranges which may obscure developmental differences. The current study examines associations between regional gray matter volumes (GMV) and psychopathology in a large sample of children with a narrowly defined age range. We used data from 9607 children 9–10 years of age collected as part of the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A bifactor model identified a general psychopathology factor that reflects common variance across disorders and specific factors representing internalizing symptoms, ADHD symptoms, and conduct problems. Brain volume was acquired using 3T MRI. After correction for multiple testing, structural equation modeling revealed nearly global inverse associations between regional GMVs and general psychopathology and conduct problems, with associations also found for ADHD symptoms (pfdr-values ≤ 0.048). Age, sex, and race were included as covariates. Sensitivity analyses including total GMV or intracranial volume (ICV) as covariates support this global association, as a large majority of region-specific results became nonsignificant. Sensitivity analyses including income, parental education, and medication use as additional covariates demonstrate largely convergent results. These findings suggest that globally smaller GMVs are a nonspecific risk factor for general psychopathology, and possibly for conduct problems and ADHD as well.
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Data availability
The ABCD Study data is available through the National Institute of Mental Health Data Archive (https://nda.nih.gov/abcd).
Code availability
For the code and a corresponding wiki describing the analytic procedures used in this study, see https://github.com/VU-BRAINS-lab/Durham_bifactor_volume.
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Acknowledgements
Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9–10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, and U01DA041025. A full list of 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 NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from RRID: SCR_015769, https://doi.org/10.15154/1519264.
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ELD took the lead on analyzing the data, writing the manuscript and supplement, making the tables and figures, and making revisions, HJJ contributed to the writing of the manuscript, TMM wrote the Mplus code for the bifactor analyses and SEM models and provided statistical consultation, RMD adapted and further developed the R code to download and prepare the ABCD Study data for analysis and provided consultation for R and Mplus, CCI developed the initial R code to download and prepare the ABCD Study data for analysis, ZC developed the code for making the brain figures and provided consultation on the use of Connectome Workbench, FES contributed to the writing of the manuscript, MGB provided conceptual and statistical consultation and contributed to the writing of the manuscript, BBL provided conceptual and statistical consultation, contributed to data analyses, contributed to the writing of the manuscript, and contributed funding to support this project, ANK provided conceptual consultation, contributed to data analyses, contributed to the writing of the manuscript, and served as the primary mentor to ELD, HJJ, RMD, and FES. All authors provided critical feedback and helped shape the research, analysis, and manuscript.
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Durham, E.L., Jeong, H.J., Moore, T.M. et al. Association of gray matter volumes with general and specific dimensions of psychopathology in children. Neuropsychopharmacol. 46, 1333–1339 (2021). https://doi.org/10.1038/s41386-020-00952-w
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DOI: https://doi.org/10.1038/s41386-020-00952-w
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