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Prenatal cannabis exposure, the brain, and psychopathology during early adolescence

Abstract

Prenatal cannabis exposure (PCE) is associated with mental health problems in early adolescence, but the possible neurobiological mechanisms remain unknown. In a large longitudinal sample of adolescents (ages 9–12 years, n = 9,322–10,186), we find that PCE is associated with localized differences in gray and white matter of the frontal and parietal cortices, their associated white matter tracts, and striatal resting-state connectivity, even after accounting for potential pregnancy, familial, and child confounds. Variability in forceps minor and pars triangularis diffusion metrics partially longitudinally mediate associations of PCE with attention problems and attention deficit hyperactivity disorder symptoms. PCE-related differences in brain development may confer vulnerability to worse mental health in early adolescence.

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Fig. 1: Association of PCE with brain metrics.
Fig. 2: Significant associations of PCE with brain metrics, by exposure group.
Fig. 3: Association of brain metrics with psychopathology in early adolescence.

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Data availability

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 aged 9–10 and follow them over 10 years into early adulthood. The ABCD data repository grows and changes over time. The ABCD data used in this report came from https://doi.org/10.15154/8873-zj65. DOIs can be found at https://nda.nih.gov/abcd/abcd-annual-releases.html. The dataset identifier is https://doi.org/10.15154/dxx6-fk12. Cannabis use disorder summary statistics are available for download at https://pgc.unc.edu/for-researchers/download-results/. Additional datasets used for processing genetic data are available at https://sites.google.com/a/broadinstitute.org/ricopili.

Code availability

Analysis code is available at https://github.com/WashU-BG/PCE_MRI.

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Acknowledgements

This study was supported by R01DA54750 (R.B., A.A.). Additional funding included the following: D.A.A.B. (K99AA030808), A.P.M. (T32DA015035), A.J.G. (DGE-213989), S.E.P. (F31AA029934), A.S.H. (K01AA030083), E.C.J. (K01DA051759; BBRF Young Investigator Grant 29571), C.E.R. (R01DA046224), A.A. (R01DA54750), and R.B. (R01DA54750, R21AA027827, U01DA055367). Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) Study, which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123 and U24DA041147 from the NIH and additional federal partners (https://abcdstudy.org/federal-partners.html). We thank T. Sheahan for her assistance with figure graphics. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the 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.

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D.A.A.B. performed statistical analyses and prepared figures and tables. D.A.A.B. and R.B. drafted the paper. D.A.A.B., S.E.P., A.S.H., A.A., and R.B. designed the study. S.M.C.C. and E.C.J. computed polygenic scores and performed quality assurance checks of genetic data. A.A. and R.B. obtained funding. All authors, including A.J.G., A.P.M., C.D.S., C.E.R. and J.D.B. revised the paper and provided critical intellectual contributions.

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Correspondence to David A. A. Baranger.

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Baranger, D.A.A., Miller, A.P., Gorelik, A.J. et al. Prenatal cannabis exposure, the brain, and psychopathology during early adolescence. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00281-7

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