Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day
Introduction
It is well-known that HPA axis activity follows a pronounced circadian rhythm with highest hormone levels in the early morning hours and continuously decreasing levels over the course of the day under unstressed conditions. The frequency and amplitude of ultradian secretory cortisol bursts change as a function of time of day (Weitzman et al., 1971, Veldhuis et al., 1989, Van Cauter et al., 1996; see also overviews by Kirschbaum and Hellhammer, 1989, Kirschbaum and Hellhammer, 1994, Van Cauter, 1995). Therefore, if a stress stimulus is applied in the morning, pre-stress cortisol levels are usually higher compared to an afternoon or evening session. Based on the assumption that the subsequent endocrine response after stimulation depends on the preexisting baseline levels, it would be expected that the subsequent endocrine response is smaller in the morning when ACTH and cortisol levels are relatively high. One might expect that a ceiling value could be reached in case of high endocrine baseline levels, flattening the extent of the superimposed stress response, for example by providing less “space” for a stress effect.
Over the last decades numerous studies have investigated the effect of time of day on HPA axis responses applying different pharmacological provocation tests. Most studies triggered ACTH and cortisol responses by the injection of CRF (oCRF/hCRF), the exogenous administration of synthetic vasopressin (CRA-41) and ACTH (Synacthen1–24), or insulin. Most CRF studies reported that the maximum cortisol increase after CRF administration was higher in the afternoon or evening than in the morning, although ACTH responses to CRF did not differ as a function of time of day (Copinschi et al., 1983, DeCherney et al., 1985, Schulte et al., 1985). However, two studies could not observe a difference in the responses of the HPA axis to CRF in the morning and in the evening although basal hormonal concentrations were higher in the morning (Tsukada et al., 1983, Watabe et al., 1985). Stimulation with ACTH or insulin led to greater maximum cortisol increases in the afternoon or evening compared to the morning (Takebe et al., 1969, Ichikawa et al., 1971, Nathan et al., 1979, Dickstein et al., 1991). Concerning vasopressin administration the picture is inconsistent (Clayton et al., 1963, Salata et al., 1988).
Beside the activation of the HPA axis by chemical agents, more recent studies investigated diurnal effects in physical exercise or meal intake. A standardized meal affected the HPA axis differently according to time of day, surprisingly showing an attenuated (Follenius et al., 1982) or even absent (Quigley and Yen, 1979) response in the evening. Relative to the observed baselines HPA axis responses after physical exercise appeared not to show a significant effect of time of day (Thuma et al., 1995, Galliven et al., 1997, Kanaley et al., 2001, Dimitriou et al., 2002). However, Scheen et al. (1998) could only evoke a significant cortisol response in the afternoon but not early in the morning (0500 h) using moderate-intensity exercise. Kanaley and coworkers found that a cortisol increase over control days were greatest at midnight, intermediate at 0700 h and smallest at 1900 h after high intensity treadmill exercise.
To the best of our knowledge there is no published report about the impact of time of day on physiological stress responses after psychosocial stress, investigating the question whether these stress responses can be assessed with equal reliability in the morning and afternoon hours, respectively. This is surprising facing the broad literature on HPA axis, cardiovascular and subjective stress responses after laboratory psychological stress in humans which has significantly accumulated over the last years. Therefore, the present reanalysis aims to investigate the impact of time of day on acute HPA axis stress responses, heart rate, and mood ratings before and after the Trier Social Stress Test, a widely-used standardized laboratory stress protocol which can reliably induce psychosocial stress in humans.
Section snippets
Subjects
The present reanalysis is based on data from five independent studies conducted in the same laboratory by Kirschbaum et al. (1999, young women and men tested in the afternoon); Kudielka et al. (1998, elderly men and women tested in the morning; Kudielka et al., 1999, Kudielka et al., 2000 elderly women, respectively men, tested in the afternoon), and Schommer et al. (2003, young women and men tested in the morning). The accepted age range for young adults was 18–32 years, for the older subjects
Pre-stress baselines
As expected, basal salivary free and plasma total cortisol levels were significantly higher during the morning compared to the afternoon session (free cortisol: morning 10.1 ± 0.5 nmol/l versus afternoon 7.1 ± 0.4 nmol/l, t(172) = −4.35; p < 0.0001, total sample 95%-CI 8.26–9.65 nmol/l, Std.Dev. 4.67; total cortisol: morning 283.5 ± 10.8 nmol/l versus afternoon 236.1 ± 11.3 nmol/l, t(165) = −2.84; p = 0.005, total sample 95%-CI 250.3–282.6 nmol/l, Std.Dev. 105.7). Neither pre-stress ACTH levels
Discussion
The present reanalysis is the first report on the impact of time of day on HPA axis responses, heart rate, and mood changes after acute psychosocial stress in humans. However, it has to be acknowledged that the present data set is based on five independent studies. Although each of the five cohorts was exposed to the highly standardized TSST stress procedure in the same laboratory, there are some (in most parts inevitable) differences between the studies (e.g., personnel involved in the
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