Patterns of Childhood Exposomes, White Matter Development and Behaviors Link to Future Cognition and Psychopathology in Youth

Environmental exposures during childhood strongly impact individuals' cognitive and socioemotional development, and psychiatric vulnerability. However, childhood exposures rarely occur in isolation. Instead, they form a highly correlated 'exposome' whose multidimensional relationships with brain development and behavioral outcomes remain poorly understood. Elucidating the complex interplay between brain, behavior, and environment requires a multivariate approach. This study used regularized multiset canonical correlation analysis on longitudinal data from 8,113 preadolescents in the Adolescent Brain Cognitive Development study to characterize latent multivariate dimensions linking diverse environmental exposures, tract-wisely resolved measures of white matter (WM) development and integrity, and multi-domain behavioral phenotypes and relate them to concurrent and future psychopathology. Two distinct multivariate dimensions were identified exhibiting different exposure, WM development, and behavior patterns. The first linked greater socioeconomic resources to more advanced WM development, particularly in dorsal-association tracts, and superior cognitive performance. The second dimension linked stronger psychosocial support with higher WM integrity, more advanced development of limbic tracts, and lower levels of psychopathology. Longitudinal analyses revealed differential contributions of these dimensions to follow-up cognitive, socioemotional and psychiatric outcomes. Moreover, WM and exposomic variates in these dimensions moderated the effects of childhood adversity on transdiagnostic psychiatric disorder risk, in sex- and context-specific fashions. Together, these findings clarify how childhood environmental exposures and the linked WM developmental differences relate to cognition and psychopathology risk, potentially informing the identification of candidate neural targets for future interventions.