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bioRxiv · 10.64898/2025.12.25.696521

Modeling Individualized Adolescent Mental Health through a Multifactorial Causal Framework to Identify Potential Intervention Strategies

Yan, J.·Wan, B.·Toussaint, P. J.·Chen, J.·Bezgin, G.·Medina, Y. I.·Bzdok, D.·Evans, A.·Karama, S.
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Abstract

Associations between psychopathology, cognition, and personality are well established. However, these associations unfold within a broader developmental context shaped by brain maturation, environmental exposures and pubertal transitions, whose influences remain poorly understood. Here, we characterized how cognition and personality relate to adolescent mental health within this developmental context. Using data from the Adolescent Brain Cognitive Development Study (N = 4501), we simultaneously modeled 16610 brain structural, environmental, and pubertal measures to examine 165 behavioral pairs comprising cognitive and personality traits with mental health symptoms. Using an integrated analytic pipeline combining multifactorial mediation and longitudinal interaction-inclusive models, we evaluated whether developmental changes in cognition and personality relate to mental health at the individual level, and whether these associations vary across brain, environmental, and pubertal profiles. Most behavioral pairs showing significant mediation effects likewise exhibited significant longitudinal effects. These pairs were primarily influenced by neurobiological and environmental measures; cortical frontal and temporal regions relevant for cognitive control and emotional regulation as well as family and lifestyle contexts were most prominently implicated. Finally, after accounting for inter-individual heterogeneity, personality traits emerged as the main behavior associated with mental health. These findings characterize developmental associations linking cognition and personality with adolescent mental health, and show that these associations vary across brain, environmental, and pubertal profiles. The study advances understanding of behavioral development and provides a framework for identifying targets for psychopathology prevention.

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Yan, J., Wan, B., Toussaint, P. J., Chen, J., Bezgin, G., Medina, Y. I., Bzdok, D., Evans, A., Karama, S.. 2025-12-26. Modeling Individualized Adolescent Mental Health through a Multifactorial Causal Framework to Identify Potential Intervention Strategies. https://doi.org/10.64898/2025.12.25.696521

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