Polysomnography-estimated sleep and the negative feedback loop of the hypothalamic-pituitary-adrenal (HPA) axis

Background:Sleep and stress are highly interrelated. To improve our understanding of the role of sleep in functioning of the negative feedback loop of the stress system, we assessed the association between sleep and functioning of the hypothalamic-pituitary-adrenal (HPA) axis in a population-based sample. Methods:This study included 403 participants (mean age: 62.4 +/- 5.0 years, 55% women) of the population-based Rotterdam Study. Between 2012 and 2014, sleep was assessed with polysomnography. Functioning of the negative feedback loop of the HPA axis was estimated by measuring cortisol levels before and after the intake of a very low dose of dexamethasone (0.25 mg) on average 0.9 +/- 37.8 days after the polysomnography. We used linear regression analyses adjusted for multiple confounders and performed sensitivity analyses in a sample excluding those with clinically relevant depressive symptoms and using psychoactive medicine, and a sample excluding non-suppressors. Results:Short N2 sleep (adjusted difference = 0.005, 95%CI = 0.002;0.009), long N3 sleep (adjusted difference = -0.007, 95%CI = -0.010;-0.003), and short sleep onset latency (adjusted difference = 0.006, 95%CI = 0.001;0.011) were associated with an enhanced response to dexamethasone, but the association of sleep onset latency did not survive multiple testing correction. Associations remained similar after excluding those with clinically relevant depressive symptoms and those using psychoactive medicine or exclusion of non-suppressors. Conclusions: This study suggests that more slow wave sleep is particularly associated with a stronger suppression of cortisol within the negative feedback loop of the HPA axis. These findings provide further support that slow wave sleep is important for health.