Adversity and brainAGE associations with age of first cannabis use in the Adolescent Brain Cognitive Development (ABCD) Study

Importance: Adolescent cannabis use is a growing concern due to its associations with long-term adverse mental health outcomes. However, the distinct, temporal associations of neurodevelopmental factors and childhood adverse life experiences (ALEs) with adolescent substance use in have not yet been fully elucidated. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to prospectively examine neurobiological and socioenvironmental predictors of cannabis onset. Objective: To investigate magnetic resonance imaging-derived neurodevelopmental cortical brain Age Gap Estimate (brainAGE) and adverse life events as risk factors of early cannabis initiation. Design, Setting, and Participants: The ABCD Study is a longitudinal study across 22 sites in the United States. Data are collected starting at approximately 10 years old (currently at year-7 follow-up). Our analyses comprised 6688 (48% female) youth after exclusions. Main Outcomes and Measures: Cox proportional hazard models were computed to investigate brainAGE-sex interactions and 10 adversity dimensions at baseline as predictors of time to cannabis initiation up to age 18. Results: Mean age of initiation was 14.8 years (SD=1.43). Global brainAGE was modestly associated with cannabis initiation in females only (Hazard Ratio [HR]=1.05; 95% Confidence Interval [CI]=1.00-1.10, p = .049). Low socioeconomic status, caregiver substance use, family anger and arguments, and caregiver lack of supervision were associated with initiation (HRs = 1.11, 1.56, 1.09, 0.85, respectively; CIs = 1.04-1.19, 1.44-1.69, 1.09-1.19, 0.76-0.91, respectively; p's < .05). Other ALE dimensions and network-specific brainAGEs were not significantly associated with initiation. Conclusions and Relevance: Findings suggest that while cortical brainAGE may be somewhat increase vulnerability to adolescent cannabis use in females, its contributions are modest at best. In contrast, early childhood adversities such as socioeconomic factors and familial characteristics may present more substantive targets for prevention and intervention.