A cumulative polyeXposure score to predict early adolescent substance use based on environmental exposures

Résumé fourni par la source

Early substance use onset is a critical public health issue linked to heightened risks of dependence, psychiatric comorbidities, and overdose later in life. While genetic predispositions are well-studied, the cumulative environmental impact, particularly during the vulnerable developmental window of adolescence, remains poorly quantified. This study analyzed 9771 youth from the Adolescent Brain Cognitive Development cohort (ages 9-15) and utilized the Exposome-Wide Association Study to derive a data-driven Time-to-Substance-Use PolyeXposure Score (T2SU-PXS) that quantifies environmental liability for substance use risk, and to compare its predictive performance with that of family history density of substance use and a polygenic score for addiction risk. Here we identify six key environmental factors associated with T2SU, including youth behaviors, home environment, and peer and community influences. The T2SU PXS outperforms both family history density of substance use and a polygenic score for addiction risk. The T2SU-PXS represents a crucial methodological advancement in operationalizing the environmental exposome in developmental psychiatry. Its scalability, interpretability, and robustness suggest practical applications in early risk stratification and preventive intervention. By enabling a more comprehensive and context-sensitive understanding of adolescent substance use vulnerability, this integrative exposomic framework may mitigate health disparities in environmentally burdened communities. Youth using substances before age 15 are prone to develop substance use problems later in life. Even though the environment largely contributes to the risk for substance use onset, improvements are needed in the methods used to assess this risk. People are exposed to multiple, diverse environmental stressors (e.g., family, peer, and neighborhood factors) simultaneously rather than one at a time and understanding how these stressors interact can provide valuable insights. In fact, deriving a single score, PolyeXposure Score (PXS), represented the accumulation of factors related to youth behaviors, home, environment, and peer and community influences that explained an adolescent’s risk for using drugs. Compared to family-inherited risk and genetic risk scores for substance use problems, PXS better estimated their risk. Studying the environment cumulatively may help researchers better address adolescent substance use. Adams et al., derive a Time-to-Substance-Use PolyeXposure Score (T2SU-PXS) from exposome-wide data in a large adolescent cohort to capture cumulative environmental risk for substance use onset. The T2SU-PXS outperforms family history and genetic risk measures in predicting early substance use, supporting early risk identification and prevention.