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Investigating cross-sectional and longitudinal relationships between brain structure and distinct dimensions of externalizing psychopathology in the ABCD sample

Neuropsychopharmacology volume 50, pages 499–506 (2025)Cite this article

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Abstract

Externalizing psychopathology in childhood is a predictor of poor outcomes across the lifespan. Children exhibiting elevated externalizing symptoms also commonly show emotion dysregulation and callous-unemotional (CU) traits. Examining cross-sectional and longitudinal neural correlates across dimensions linked to externalizing psychopathology during childhood may clarify shared or distinct neurobiological vulnerability for psychopathological impairment later in life. We used tabulated brain structure and behavioural data from baseline, year 1, and year 2 timepoints of the Adolescent Brain Cognitive Development Study (ABCD; baseline n = 10,534). We fit separate linear mixed effect models to examine whether baseline brain structures in frontolimbic and striatal regions (cortical thickness or subcortical volume) were associated with externalizing symptoms, emotion dysregulation, and/or CU traits at baseline and over a two-year period. The most robust relationships found at the cross-sectional level was between cortical thickness in the right rostral middle frontal gyrus and bilateral pars orbitalis was positively associated with CU traits (β = |0.027–0.033|, pcorrected = 0.009–0.03). Over the two-year follow-up period, higher baseline cortical thickness in the left pars triangularis and rostral middle frontal gyrus predicted greater decreases in externalizing symptoms ((F = 6.33–6.94, pcorrected = 0.014). The results of the current study suggest that unique regions within frontolimbic and striatal networks may be more strongly associated with different dimensions of externalizing psychopathology. The longitudinal findings indicate that brain structure in early childhood may provide insight into structural features that influence behaviour over time.

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Fig. 1: Confidence intervals of the beta weight estimates derived from the linear mixed models showing associations between externalizing symptoms/emotion dysregulation/CU traits and both cortical thickness and subcortical volume.
Fig. 2: Trajectories of externalizing symptoms as predicted by baseline cortical thickness.

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Data availability

Data for the ABCD Study are available through the National Institutes of Health Data Archive (NDA; nih.nda.gov). The participant IDs included in these analyses and details on the measures used can be found in this project’s NDA study (https://doi.org/10.15154/q36k-ga33).

Code availability

The code for the analysis can be found on GitHub (https://github.com/hajernakua/ext_psychopathology_ABCD).

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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 U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, 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/consortiummembers/. 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 NDA Release 4.0 (https://doi.org/10.15154/q36k-ga33).

Funding

LP has received funding from a Canadian Institutes of Health Research (CIHR) Doctoral Award and Ontario Graduate Scholarship. HN has received funding from the CAMH Discovery Fund, Ontario Graduate Scholarship, Fulbright Canada, and currently receives funding from the CIHR Doctoral Award. SHA currently receives funding from the NIMH, CIHR, the CAMH Foundation, and the Canada Research Chairs Program. BA currently receives funds from the CIHR, CAMH Discovery Fund, LesLois Shaw Foundation and Peter Gilgan Foundation.

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Author notes

  1. These authors contributed equally: Hajer Nakua, Lee Propp.

Authors and Affiliations

  1. Margaret and Wallace McCain Centre for Child Youth and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Hajer Nakua, Lee Propp, Stephanie H. Ameis & Brendan F. Andrade

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Hajer Nakua & Stephanie H. Ameis

  3. Department of Applied Psychology and Human Development, Ontario Institute for Studies in Education, University of Toronto, Toronto, ON, Canada

    Lee Propp & Anne-Claude V. Bedard

  4. Biostatistics Core, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Marcos Sanches

  5. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Stephanie H. Ameis & Brendan F. Andrade

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Contributions

LP and HN conducted all the analyses and wrote the main draft of the paper. BA, ACB, and SA contributed to the design of the study. MS contributed to the design of the analytical approaches used. All authors wrote, revised, approved, and agreed to be accountable for all aspects of the final manuscript.

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Correspondence to Brendan F. Andrade.

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Nakua, H., Propp, L., Bedard, AC.V. et al. Investigating cross-sectional and longitudinal relationships between brain structure and distinct dimensions of externalizing psychopathology in the ABCD sample. Neuropsychopharmacol. 50, 499–506 (2025). https://doi.org/10.1038/s41386-024-02000-3

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