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Cognitive and global morphometry trajectories as predictors of persistent distressing psychotic-like experiences in youth

Nature Mental Health volume 3, pages 1012–1019 (2025)Cite this article

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Abstract

Psychotic-like experiences (PLEs) may result from genetic and environmental risk factors that contribute to progressive declines in cognition and brain morphometry, which in turn exacerbate PLEs over time. Here we used three waves of unique longitudinal Adolescent Brain Cognitive Development Study data (ages 9–13 years) to test whether changes in cognition and global morphometry metrics attenuate associations between genetic and environmental risk with persistent distressing PLEs. Multigroup univariate latent growth models examined three waves of cognitive metrics and global morphometry separately for three PLEs groups: persistent distressing PLEs (n = 356), transient distressing PLEs (n = 408) and low-level PLEs (n = 7,901). Persistent distressing PLEs showed greater decreases (that is, more negative slopes) of cognition and morphometry metrics over time compared with those in low-level PLEs groups. Analyses also provided evidence for extant theories that worsening cognition and global morphometry metrics may partially account for associations between environmental risk with persistent distressing PLEs.

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Fig. 1: Associations between cognitive and global morphometry metrics with PLEs over time.
Fig. 2: Evidence for cognitive and global morphometry metrics attenuating associations between environmental risk with PLEs over time.

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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 years and follow them over 10 years into early adulthood. The ABCD data repository grows and changes over time. The ABCD data used in this Article are available at https://nda.nih.gov/study.html?id=2313.

Code availability

Code is available via GitHub at https://github.com/nkarcher/Genetic-and-Environmental-Influences-on-Associations-between-Cognition-and-Neural-Metrics-with-PLEs.

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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 aged 9–10 years and follow them over 10 years into early adulthood. The ABCD study is supported by the National Institutes of Health (NIH) 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/principal-investigators.html. 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 Article 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. This Article is the result of funding in whole or in part by the NIH. It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given a right to make this Article publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH. This work was supported by National Institutes of Health grants U01 DA041120 (D.M.B.), K23 MH121792 (N.R.K.), R01-MH139880 (N.R.K.), R01-DA054869 (A.A.), K01-DA051759 (E.C.J.), R01-DA054750 (A.A. and R.B.) and F31-AA029934 (S.E.P.).

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Authors and Affiliations

  1. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA

    Nicole R. Karcher, Fanghong Dong, Emma C. Johnson, Can M. Kilciksiz, Arpana Agrawal & Deanna M. Barch

  2. Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA

    Sarah E. Paul, Ryan Bogdan, Joshua J. Jackson & Deanna M. Barch

  3. Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, USA

    Can M. Kilciksiz

  4. Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, CA, USA

    Hans Oh

  5. Department of Psychological Science, University of California, Irvine, Irvine, CA, USA

    Jason Schiffman

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Contributions

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

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Correspondence to Nicole R. Karcher.

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Nature Mental Health thanks Pedro Mario Pan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Methods, Results, Tables 1–12 and Figs. 1–5.

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Karcher, N.R., Dong, F., Paul, S.E. et al. Cognitive and global morphometry trajectories as predictors of persistent distressing psychotic-like experiences in youth. Nat. Mental Health 3, 1012–1019 (2025). https://doi.org/10.1038/s44220-025-00481-9

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