Causally informed, multifactorial pathways linking cognition and personality to adolescent mental health

Abstract Adolescence is a sensitive period for the emergence of psychopathology. During this time, physiological changes and environmental exposures jointly shape brain development and influence cognitive and personality maturation, collectively heightening vulnerability to mental disorders. However, the complexity of interactions between these factors has hindered a systems-level understanding of mental health and the causal roles of cognition and personality in psychopathology. In this study, we proposed a multifactorial causal framework integrating brain, pubertal, environmental, and behavioral factors to characterize heterogeneity in adolescent mental health trajectories at the individual level. We then investigated latent causal pathways linking cognition and personality to mental health outcomes and identified potential personalized intervention targets. Leveraging the Adolescent Brain Cognitive Development (ABCD) dataset (N = 4,501), we analyzed 165 behavioral pairs connecting cognition and personality traits to mental health symptoms. Using cross-sectional multivariate mediation and longitudinal interaction-inclusive analyses, we identified 68 behavioral pairs showing significant causal relationships, with brain and environmental exposures contributing to most pathways, while pubertal factors exhibited limited involvement. Individualized interpretive analyses further revealed 23 pairs suggesting potential interventions with response rates exceeding 50%. Among these, behavioral inhibition, negative urgency, and processing speed emerged as the most common intervention targets, whereas psychosis symptoms and attention problems were the most likely issues to improve. Overall, our study advances a comprehensive framework capturing the multifactorial and heterogeneous nature of adolescent mental health, delineates specific causal pathways from cognitive and personality traits to psychopathology, and provides a principled basis for potential individualized intervention strategies. Competing Interest Statement The authors have declared no competing interest. Footnotes We revised the title to more precisely capture the causally informed, multifactorial modeling framework at the core of the study, rather than its translational implications.