The longitudinal association of sleep and 24-hour activity rhythms with cortisol response to a very low dose of dexamethasone.

Objectives: Poor sleep is common in the general population, with hyperarousal and stress often suggested as causal factors. Conversely, sleep might also affect the stress response, in which the hypothalamic-pituitary-adrenal (HPA) axis plays a key role. We assessed the longitudinal association of sleep and 24-hour activity rhythms with functioning of the negative feedback loop of the HPA axis, as indicated by the cortisol response to a very low dose of dexamethasone.

Design: Longitudinal cohort.

Setting: Population-based.

Participants: This study included 410 participants (mean age: 56.1 ± 5.5 years, 59% women) from the Rotterdam Study. For 217 participants, the cortisol response to dexamethasone was assessed again after a median follow-up of 5.7 years (IQR = 5.5-5.8).

Measurements: Between 2004 and 2007, sleep and 24-hour activity rhythms were estimated with actigraphy (mean duration: 146 ± 19.6 hours) and sleep quality with the Pittsburgh Sleep Quality Index. To assess the negative feedback loop of the HPA axis we measured cortisol before and after the intake of a very low-dose of dexamethasone (0.25 mg).

Results: Unstable (B = 1.64, 95% CI = 0.78; 2.50) and fragmented (B = -1.31, 95% CI = -2.17; -0.45) 24-hour activity rhythms, and a poor self-rated sleep quality (B = -0.02, 95% CI = -0.04; 0.00) were associated with an enhanced cortisol response to dexamethasone over time, also in those without clinically relevant depressive symptoms and those not using psychoactive medication.

Conclusions: This study demonstrates a longitudinal association of disturbed 24-hour activity rhythms and poor self-rated sleep quality with an enhanced cortisol response to dexamethasone, in other words stronger suppression of cortisol.

Statement Of Significance: This study shows that disturbed 24-hour activity rhythms and a poor self-rated sleep quality are associated with functioning of the negative feedback loop over a period of years.