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 preadolescent endocrine influences to adolescent psychopathology remains limited. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (Nmax=10,562), we analyzed whether salivary DHEA during preadolescence predicted later externalizing and internalizing symptoms during adolescence. To create a more robust estimate for hormonal levels in preadolescence, hormone concentrations 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 (age range=10.6-15.8 years). Sex-stratified linear mixed models were employed, adjusting for age, race/ethnicity, BMI and physical activity. In males, higher DHEA levels were linked to fewer externalizing symptoms across all 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 to fewer internalizing symptoms at 3-year and 4-year follow-ups. The effect of preadolescent DHEA in males translated into a reduced probability of externalizing symptoms crossing borderline or clinical thresholds at each follow-up (e.g., adjusted Risk Ratio=0.76 to reach clinical threshold for CBCL externalizing per SD increase in log-transformed DHEA; 95% CI 0.62, 0.98 at 3-year). In females, no hormone-symptom associations emerged. Interestingly, sex-by-DHEA interaction effects increased with age for both symptom domains. These findings suggest that preadolescent adrenal endocrine influences may play a role in the development of sex-specific vulnerability during adolescence. Future studies should consider adrenarche as a sensitive period for hormonal effects on mental health.