Abstract

Abstract Introduction The Cortisol Awakening Response (CAR) is a rapid increase in cortisol levels at awakening that lasts for about 1 hour. This secretory phenomenon has been proposed to be independent of circadian cortisol regulation. However, the contribution of the circadian system to the CAR remains unclear. The aim of this study is to assess the circadian variation of the CAR. Methods A total of eleven healthy participants (1 woman; 22.6 ± 3.4 years old) were enrolled. Following an 8-h baseline sleep period aligned to their habitual sleep times, participants underwent a 72-h ultradian sleep-wake cycle procedure (USW) consisting of 60-min wake periods in dim light (<10 lux) alternating with 60-min nap opportunities in total darkness. Participants remained in a semi-recumbent posture during the procedure. Salivary cortisol samples were collected at 0, 15, 30, and 50 minutes after waking up from each nap. Linear mixed-effects regression analyses were performed on log-transformed cortisol data from wake periods corresponding to the habitual bedtime (biological night) and habitual wake-time (biological morning). These served as proxies of circadian phases characterised by lowest and maximal cortisol secretory activity, respectively. Total cortisol secretion and CAR magnitude during these periods were computed, respectively, as the Area Under the Curve with respect to ground (AUCg) and to increase (AUCi) and compared with paired-samples t-tests. Results Significant main effects of wake period (p<.001) and sample time (p=.023) were found, with no interaction (p=.167). Cortisol levels were higher in the biological morning compared to the biological night and increased with elapsed time awake. The total amount of cortisol secreted (AUCg) after waking in the biological morning was significantly greater than during the biological night (p<.001). No significant differences between circadian phases were found in the AUCi (p=.223). Conclusion Our study suggests that some features of the CAR may at least partially be under circadian control. These findings are relevant for the understanding of the physiological mechanisms underlying circadian misalignment in shift workers and patients with severe sleep disorders. Support (if any) Project funded by the Canadian Institutes of Health Research. I.R.B received a Barrie Foundation Fellowship. A.K. received a Fonds de Recherche en Santé du Québec postdoctoral fellowship.

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