Effects of adverse childhood experiences on behavior in adolescence: Insights from brain imaging and genetic risk

Adolescence is a critical developmental stage, and adverse childhood experiences (ACEs) are important environmental factors influencing behavior. However, the relationship between ACEs, individual behavior, brain mechanisms, and the role of genetic risk remains underexplored. In this study, data from 9796 youths aged 9-13 years in the Adolescent Brain Cognitive Development (ABCD) study were analyzed, including 67 ACE-related variables and 30 behavioral outcomes. Using sparse canonical correlation analysis, we identified two distinct patterns: a parental mental health-child psychopathology, linking parental psychiatric status to child mental health (r = 0.576, P_perm < 0.001) and a socioeconomic-cognitive development, in which higher family socioeconomic status and a more supportive family atmosphere correlated with better child cognition (r = -0.272, P_perm < 0.008). Neuroimaging revealed these associations were mediated by structural alterations in brain regions including the temporal and parietal cortex, hippocampus, and cerebellar cortex, along with changes in white matter tracts and functional networks. Genetic risk for psychiatric disorders significantly moderated these ACEs-brain-behavior pathways, with effects varying across ancestry groups. Longitudinal cross-lagged panel models further demonstrated that parental psychiatric conditions, particularly depression and attention deficit hyperactivity disorder, predicted child psychiatric symptoms two years later. Our findings delineate distinct ACEs-related pathways influencing adolescent behavior through neurostructural and functional mediators, moderated by genetic risk. This integrated framework advances the understanding of ACEs mechanisms and highlights targets for early intervention.