The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder patients-A replication study

Front Neurosci. 2022 Oct 12:16:952903. doi: 10.3389/fnins.2022.952903. eCollection 2022.

Abstract

The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = -0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = -0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context.

Keywords: HPA axis; biomarker; cortisol awakening response; depression; follow-up; replication study.