Pubertal mediators of early life stress and age on adolescent alcohol initiation: Analysis by sex

Psychoneuroendocrinology. 2025 Oct:180:107559. doi: 10.1016/j.psyneuen.2025.107559. Epub 2025 Jul 20.

Abstract

Background: Early life stress (ELS) is associated with an increased risk of substance use in adolescence. The interaction of puberty with neurodevelopment during adolescence increases the sensitivity of the brain to both sex and stress hormones. This sensitivity may result in sex-specific pathways from ELS to adolescent alcohol use initiation. The current study examines the effect of ELS on alcohol initiation by age 13 via pubertal mediators, separated by sex and adjusted for the independent effects of age.

Methods: Adolescents from the Adolescent Brain Cognitive Development study (ABCD; N = 4828 US children aged 9-10 at baseline) were assessed for ELS, age (in months), pubertal mediators (pubertal development score or PDS, testosterone) from baseline through year 2, and alcohol use initiation from baseline through year 3. Confirmatory factor analysis was used to generate a latent factor of ELS from baseline measures of threat and deprivation, which was then placed into a combined measurement and structural model to assess the mediation of ELS and age effects by pubertal measures in a sex-stratified analysis of alcohol use initiation.

Results: ELS was not significantly associated with alcohol initiation in either sex. Age was directly associated with alcohol initiation among males (0.07 SE 0.02 p < 0.01) and indirectly associated among females (0.03 SE 0.01 p < 0.01). This indirect effect of age was mediated by longitudinal measures of pubertal development (PDS and testosterone). ELS was significantly associated with both PDS and testosterone at baseline in both sexes.

Conclusions: Our findings highlight sex-specific effects of age on alcohol use initiation, with females showing an indirect effect of age on alcohol initiation mediated by pubertal measures, and males showing a direct effect of age. Future studies should investigate sex differences in the interactions of testosterone and PDS with social and individual factors influencing alcohol use initiation. Recognizing the different pathways influencing male and female early adolescent alcohol use initiation can help health providers and parents tailor alcohol prevention strategies to address the needs of their adolescent.

Keywords: Adolescence; Alcohol; Puberty; Sex; Stress; Substance use.

MeSH terms

  • Adolescent
  • Adolescent Behavior / physiology
  • Adolescent Behavior / psychology
  • Adolescent Development / physiology
  • Adverse Childhood Experiences*
  • Age Factors
  • Alcohol Drinking* / psychology
  • Child
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Puberty* / metabolism
  • Puberty* / physiology
  • Puberty* / psychology
  • Sex Factors
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology
  • Stress, Psychological* / psychology
  • Testosterone / analysis
  • Testosterone / metabolism
  • Underage Drinking* / psychology
  • Underage Drinking* / statistics & numerical data

Substances

  • Testosterone