Cortisol awakening response in pregnant women with depressive disorders: a potential marker of recovery status from pregnancy to postpartum

Introduction: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to peripartum depression, potentially contributing to symptom persistence. This study examines the relationship between the cortisol awakening response (CAR) during pregnancy and depressive symptom reduction postpartum. Methods: Pregnant women with a current depressive episode were included in this study, part of a larger RCT on bright light therapy. At baseline (12-32 weeks of pregnancy), participants provided saliva samples at awakening, +30, and +60 min post-awakening. The CAR was assessed using three measures: area under the curve relative to ground (AUCg), area under the curve relative to increase (AUCi), and peak reactivity (difference between awakening and +30 min cortisol levels). Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D) at baseline and two months postpartum. Linear regression models assessed associations between CAR measures and depressive symptom change, adjusting for relevant covariates. Results: The study included 55 pregnant women (mean age: 32.3 years, SD 4.8; mean gestational age: 19.7 weeks). Mean HAM-D scores decreased from 16.7 (SD 5.3) at baseline to 5.7 (SD 5.6) postpartum. Higher AUCi during pregnancy was associated with less symptom reduction postpartum (unadjusted β = 0.36, p = .02; adjusted β = 0.36, p = .02), as was peak cortisol reactivity (unadjusted β = 0.33, p = .03; adjusted β = 0.32, p = .03), while AUCg showed no significant association with symptom change (unadjusted p = .19; adjusted p = .28). Conclusion: Higher AUCi and peak cortisol reactivity of the cortisol awakening response during pregnancy were linked to persistence of depressive symptoms postpartum, suggesting that heightened cortisol reactivity to awakening may indicate persistent stress vulnerability in peripartum depression. Total cortisol output (AUCg) was not predictive of recovery. These findings underscore the potential relevance of stress reactivity over basal cortisol levels in peripartum depression and highlight the need for further research in larger samples to elucidate the usefulness in clinical practice.