The sex-specific role of adrenal androgens in youth psychopathology

Adolescence is a vulnerable period for the emergence of mental health problems. Adrenarche, an early stage of pubertal development marked by rising adrenal androgens, particularly dehydroepiandrosterone (DHEA), may influence emotional and behavioral development. However, longitudinal evidence linking early-adolescent endocrine influences to adolescent psychopathology remains limited. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (up to N = 11 696), we analyzed whether salivary DHEA during early adolescence predicted later externalizing and internalizing symptoms during adolescence. Early-adolescent hormone levels were averaged across baseline and 1-year follow-up (age range = 8.9-12.4 years). Outcomes were measured via the Child Behavior Checklist (CBCL) at the 2-, 3-, and 4-year follow-ups (up to = 14.08 ± 0.68 years). Sex-stratified linear mixed models adjusted for age, race/ethnicity, BMI and physical activity. In males, higher DHEA levels were linked to fewer externalizing symptoms across follow-ups (e.g., β = -0.07 SD change of CBCL per SD-change of log-transformed DHEA levels (95% CI [-0.10, -0.04] at 3-year) and fewer internalizing symptoms at 3-year and 4-year follow-ups. Higher early-adolescent DHEA in males also reduced the probability of externalizing symptoms to reach clinical thresholds across follow-ups (e.g., adjusted Risk Ratio = 0.81 to reach clinical threshold for CBCL externalizing per SD increase in log-transformed DHEA; 95% CI [0.70, 0.93] at 3-year). In females, no hormone-symptom associations emerged. Sex-by-DHEA interaction effects tended to increase across follow-up years for both symptom domains. These findings suggest that early-adolescent adrenal endocrine influences may contribute to the development of sex-specific vulnerability during adolescence. Future studies should consider adrenarche as a sensitive period for hormonal effects on mental health.