Are sex differences in adolescent depression and anxiety driven by adrenarchal hormones? A causal mediation analysis from a prospective cohort study.

BACKGROUND

Incident depression and anxiety rise from early adolescence, when sex differences around these disorders first emerge. We aimed to examine the effects of adrenarchal hormones on depression and anxiety symptoms during early adolescence, and to assess whether sex differences in these outcomes are mediated by these hormones.

METHODS

Data were from the Child to Adult Transition Study, a population-based cohort from Melbourne, Australia that has annually tracked 667 females and 572 males who were recruited in Grade 3. Salivary DHEA, DHEAS, and testosterone were measured at baseline (age 9 years). Depression and anxiety symptoms at wave 5 (age 13 years) were self-reported. Interventional indirect effects (IIEs) for the three hormones were estimated using causal mediation analysis.

RESULTS

Depression (11 % females, 4 % males) and anxiety (10 % females, 3 % males) symptoms were more common in females. In males, the risk ratio (RR) per doubling of DHEA levels was 1.54 for depression (95 % CI 1.04-2.28, p = 0.03) and 1.57 for anxiety (95 % CI 1.09-2.27, p = 0.02). In females, the associations between hormones and outcomes were inconclusive. A hypothetical intervention shifting the joint distribution of DHEA, DHEAS, and testosterone in females to that of males had minimal impact on reducing the risk in females compared with males (depression: IIE RR 1.03 [95 % CI 0.92-1.14], p = 0.64; anxiety: 1.07 [0.96-1.20], p = 0.23).

CONCLUSIONS

Higher DHEA levels were associated with increased risk of depression and anxiety during early adolescence in males. We found no evidence that adrenarchal hormone levels mediated the sex differences in depression and anxiety.