Multivariate Patterns of Brain-Behavior-Environment Associations in the Adolescent Brain and Cognitive Development Study

Background: Adolescence is a critical developmental stage. A key challenge is to characterize how variation in adolescent brain organization relates to psychosocial and environmental influences. Methods: We used canonical correlation analysis to discover distinct patterns of covariation between measures of brain organization (brain morphometry, intracortical myelination, white matter integrity, and resting-state functional connectivity) and individual, psychosocial, and environmental factors in a nationally representative U.S. sample of 9623 individuals (aged 9–10 years, 49% female) participating in the Adolescent Brain and Cognitive Development (ABCD) study. Results: These analyses identified 14 reliable modes of brain-behavior-environment covariation (canonical r_discovery =.21 to.49, canonical r_test =.10 to.39, p_{false discovery rate corrected} <.0001). Across modes, neighborhood environment, parental characteristics, quality of family life, perinatal history, cardiometabolic health, cognition, and psychopathology had the most consistent and replicable associations with multiple measures of brain organization; positive and negative exposures converged to form patterns of psychosocial advantage or adversity. These showed modality-general, respectively positive or negative, associations with brain structure and function with little evidence of regional specificity. Nested within these cross-modal patterns were more specific associations between prefrontal measures of morphometry, intracortical myelination, and functional connectivity with affective psychopathology, cognition, and family environment. Conclusions: We identified clusters of exposures that showed consistent modality-general associations with global measures of brain organization. These findings underscore the importance of understanding the complex and intertwined influences on brain organization and mental function during development and have the potential to inform public health policies aiming toward interventions to improve mental well-being.