Links between hormonal and pubertal development, and adolescent females' risk for affective symptoms

Depression and anxiety symptoms surge during adolescence, particularly in females, yet the biological mechanisms underlying this vulnerability remain poorly understood. Although estrogen has traditionally been emphasized, androgens such as dehydroepiandrosterone (DHEA) and testosterone may represent distinct pathways to affective symptom risk. The present study examined whether increases in testosterone predict internalizing symptoms in adolescent females by examining hormonal and physical aspects of pubertal development and testing whether testosterone effects persist beyond estradiol and observable maturation. Using data from 5476 females (ages 9-13) in the Adolescent Brain Cognitive Development Study, we analyzed annual salivary DHEA, testosterone, and estradiol alongside caregiver-reported pubertal development and youth-reported internalizing symptoms. Latent change score models captured developmental dynamics: univariate models characterized growth trajectories, bivariate coupling models tested directional hormonal influences, and the final model evaluated whether testosterone and pubertal development changes predicted internalizing symptoms, controlling for estradiol, age, and assay covariates. Testosterone increased gradually across early adolescence, whereas DHEA showed accelerating, nonlinear growth. Increases in testosterone predicted higher internalizing symptoms between ages 10 and 12 (b = 0.041, 95% CI [0.007, 0.076]; b = 0.075, 95% CI [0.009, 0.142]). Observable pubertal development was negatively associated with internalizing symptoms at one assessment. Estradiol predicted subsequent pubertal development and showed concurrent associations with internalizing symptoms at two assessments but did not explain the testosterone-internalizing link. Increases in testosterone predicted internalizing symptoms after accounting for observable maturation and estradiol, identifying a specific vulnerability window between ages 10-12 with implications for early identification and timing of preventive interventions.