Abstract Free cortisol as measured in saliva increases markedly following awakening. It is not clear, however, whether this is truly a stress-neuroendocrine response to awakening or a manifestation of the hypothalamic-pituitary-adrenal (HPA) circadian cycle. We investigated whether the awakening cortisol response can be generated in the middle of nocturnal sleep, when secretory activity in the HPA axis is low. In a within subject design, salivary cortisol response was measured under three different awakening conditions: (1) awakening at the normal morning awakening time; (2) awakening four hours prior to normal awakening time, and (3) awakening the following morning after interrupted sleep. The overall main effect was a linear increase in free cortisol following awakening with no significant interaction with awakening condition. Cortisol levels, as determined by area under the cortisol curve calculated with reference to zero, did differ by awakening condition. The two morning awakening conditions were comparable but values were lower for night awakening. Area under the curve change (calculated with reference to the first awakening cortisol base value), however, did not distinguish the three awakening conditions. We conclude from these data that there is a clear free cortisol response to awakening for both nocturnal and morning awakening although the absolute levels produced are lower for nocturnal awakening when basal cortisol is low. Nocturnal interruption of sleep did not affect the subsequent morning response.
