Cortisol and changes in depressive symptoms: The moderating role of DHEA

Psychoneuroendocrinology. 2024 Mar:161:106941. doi: 10.1016/j.psyneuen.2023.106941. Epub 2023 Dec 19.

Abstract

Stress is associated with activation of the hypothalamus-adrenal-axis (HPA). Cortisol, a product of the HPA, is thought to predict depression. However, to date, the majority of studies investigating the cortisol-depression relationship have been cross-sectional and results have been mixed. One possible reason for these mixed findings, may be that many studies fail to consider the moderating role of dehydroepiandosterone (DHEA), which is released alongside cortisol and is thought to serve opposing functions. Therefore, the present study investigated the main and interactive effects of cortisol and DHEA on depressive symptoms. Salivary cortisol and DHEA were measured from saliva throughout the Trier Social Stress task for N = 417 participants at baseline. Participants reported on their depressive symptoms using the Beck Depression Inventory - II at both baseline and follow up (ranging from 1-20 months post baseline; M = 11.60, SD = 5.80) as well as general demographics. The lavaan package in R (version 0.6.11; Rosseel, 2012) was used to conduct multiple regression analyses with FIML to explore the relationships between these variables. Results demonstrated no main effect of cortisol or DHEA, but did show a significant interaction with DHEA. The relations between cortisol and depressive symptoms depended on levels of DHEA such that the relationship was positive at low and negative at high levels of DHEA, with the overall interaction significant (β = -.22, p < .001, 95% CI = [-.333, -.115]). DHEA can act as a protective factor against depression when cortisol levels are high. This presents opportunities for future research on how to improve DHEA levels to potentially reduce depression.

Keywords: Cortisol; DHEA; Depression.

MeSH terms

  • Cross-Sectional Studies
  • Dehydroepiandrosterone* / analysis
  • Depression*
  • Humans
  • Hydrocortisone / analysis
  • Hypothalamo-Hypophyseal System / chemistry
  • Pituitary-Adrenal System / chemistry
  • Saliva / chemistry

Substances

  • Dehydroepiandrosterone
  • Hydrocortisone