8256 Early Life Stress and Pubertal Predictors of Youth Substance Use Initiation: Does Sex Moderate the Relationship Between ELS, Puberty, and Substance Use Initiation?
Authors: Donovan Alexandra , Assari Shervin , Shaheen Magda , Grella Christine , Richter Linda , Friedman Theodore C 
Published: October 2024

Disclosure: A. Donovan: None. S. Assari: None. M. Shaheen: None. C. Grella: None. L. Richter: None. T.C. Friedman: None.

Background: Early life stress (ELS) is a construct composed of children’s experiences of abuse, neglect, and conflict. Approximately 20% of adolescents in the United States have experienced ELS at some point, and these experiences influence adolescent and adult health behavior outcomes. Adults with a history of ELS display higher rates of substance use disorders (SUD) and report earlier initiation of substance use. Additionally, ELS has been associated with early puberty, which in turn is linked to earlier substance use initiation. Our study examines the roles of pubertal status, sex hormones (estradiol, testosterone, and DHEA) and ELS as predictors of the initiation of substance use among a nationally representative sample of male and female adolescents in NIDA’s Adolescent Brain Cognitive Development (ABCD) database. Methods: Baseline measures from the ABCD database release 5.0 were used to generate an ELS score (0-60), puberty assessed via parental report on the Pubertal Development Scale (PDS, 1-4), and sex hormones (estradiol, testosterone, and DHEA) were analyzed via salivary samples. The relationship between these scores and time to first use of alcohol, nicotine, and marijuana was determined via survival analysis utilizing a cox regression. Age was tested as a covariate in the interaction of ELS and time to first use of alcohol, nicotine, and marijuana. Data were analyzed overall and for biological boys and girls separately (N=11,866, 52%M 48%F. ages 9-11 at baseline). Results: We observed additive effects of PDS score, estradiol measure, age, and ELS on time to first use of any substance (alcohol, nicotine, or marijuana) and found age (Exp β= 1.029, p&lt;0.001) and ELS (Exp β= 1.017, p&lt;0.05) to be significant predictors of time to first use. After separating by sex, ELS was no longer a significant predictor for males (Exp β= 1.014, p=0.054), but remained a predictor for females (Exp β= 1.019, p&lt;0.05) indicating the overall effect was driven by females. Additionally, salivary estradiol was a significant predictor of first use for females (Exp β= 1.208, p&lt;0.05), while salivary DHEA and testosterone were not predictors for males or females. Conclusions: Our results indicate sex does moderate the relationship between ELS and substance use initiation within our population, with females showing increased risk of initiation with increases in estradiol. Further findings from our study will help to describe sex differences among the factors that increase the risk of substance use initiation among ELS-exposed youth and explore how these vary by substance. ABCD provides an unprecedented opportunity to explore the mechanisms behind complex effects of ELS by sex on risk factors for adolescent substance use initiation.

Presentation: 6/1/2024