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Substance use disorders are reaching epidemic proportions among adolescents and young adults. While disturbed, insufficient sleep is known to be associated with substance use, little is known about the role of circadian misalignment in precipitating or perpetuating substance misuse. Methods The Penn State Child Cohort is a population-based sample of 700 children (Mdn=9y), who were followed-up 8 years later as adolescents (N=421, Mdn=16y) and 15 years later as young adults (N=492, Mdn=24y). In adolescence, a delayed sleep phase was defined as a 7-night actigraphy-measured mean sleep midpoint later than 4:00 AM, while an irregular circadian phase as a within-subjects standard deviation in sleep midpoint greater than 1 hour. Alcohol, tobacco, and drug use was ascertained by parent- and/or self-reports in adolescence, while alcohol, tobacco and marijuana use was ascertained by self-reports in young adulthood. Logistic regression models tested the association between delayed and irregular circadian phase with substance use adjusted for age, sex, race/ethnicity, BMI, SES, mental health problems and psychoactive medications. Results Adolescents with a delayed sleep phase (n=164) showed later bed and wakeup times, lower morningness scores and greater circadian phase irregularity. Cross-sectionally, a delayed sleep phase in adolescence was associated with 1.9-fold odds (95%CI=1.1–3.2) of alcohol, tobacco and/or drug use; specifically, the odds of alcohol and tobacco use associated with a delayed sleep phase were 1.9-fold (95%CI=1.1–3.4) and 2.4-fold (95%CI=1.1–5.3), respectively, while non-significant for drug use (n=28) for which mental health problems were among the strongest risk factors (OR=3.0, 95%CI=1.3–6.8). Longitudinally, an irregular circadian phase in adolescence was associated with 2.2-fold odds (95%CI=1.1–4.5) of alcohol, tobacco and/or marijuana use in young adulthood; specifically, the odds of alcohol use in young adulthood associated with an irregular circadian phase in adolescence were 1.9-fold (95%CI=1.1–3.5), while non-significant for tobacco (n=58) or marijuana use (n=76) for which mental health problems were the strongest risk factor (OR=2.2, 95%CI=1.3–3.7). Conclusion A delayed or irregular circadian phase in adolescence is associated with substance use, particularly alcohol use in the transition to adulthood. Beyond disturbed and insufficient sleep, circadian misalignment should become a target of early interventions to prevent substance use disorders. Support (if any) R01MH118308, R01HL136587, R01HL97165, R01HL63772, UL1TR000127

627 Adolescent Delayed Sleep Phase and Circadian Irregularity Associated with Substance (Mis)Use in Young Adulthood