Sleep disturbances are correlated with decreased morning awakening salivary cortisol
Introduction
Chronic insomnia is a widespread disorder (Hohagen et al., 1993, Leger et al., 2000, Backhaus et al., 2002b) that increases with age, especially beyond the age of 40 years. Around this age the amount of slow wave sleep naturally decreases and wakefulness during bedtime increases, both of which might contribute to insomnia (e.g. Van Cauter et al., 2000). According to DSM-IV criteria (Association AP, 2000), patients with primary insomnia suffer from problems of sleep onset, sleep maintenance, and/or non-refreshing sleep. They experience daytime impairments, such as tiredness, disturbed concentration, or reduced efficiency, as a consequence of the disturbed night sleep. For diagnosis, an insomnia duration of at least 4 weeks is necessary.
Primary insomnia is associated with a disturbance of cortisol secretion, whereby an increase in 24-h urinary cortisol levels has been shown (Vgontzas et al., 1998, Shaver et al., 2002). Vgontzas et al. (2001) found an increase in serum cortisol in the evening and in the first hours of nocturnal sleep in a sample of younger patients with primary insomnia. This result was confirmed by Rodenbeck et al. (2002) on a small sample of patients, while Riemann et al. (2002) could not replicate these findings. The latter study, however, exclusively used the DSM-IV criteria for sample selection, while Vgontzas et al. (2001) only included subjects with a disturbed sleep EEG in addition to the DSM-IV criteria, thus probably sampling patients with a more severe disturbance of sleep.
Studies on serum or plasma cortisol allow for assessments during sleep, but they require use of an intravenous cannula that in itself can be a stressor influencing cortisol secretion and sleep parameters (Jarrett et al., 1984, Vitiello et al., 1996, Prinz et al., 2001). Furthermore, the sampling of blood at short time intervals usually restricts assessment to unnatural laboratory conditions and to a relatively small number of nights that might not reflect the natural variation in nightly sleep. While the sampling of urinary cortisol would allow for assessment across more nights, this method only allows for a more general assessment of cortisol secretion over a longer time period. Salivary cortisol, by contrast, can easily and without stress be collected at home and across a longer time period. Furthermore, it can be collected at specific time points close to the sleep period, thus allowing for some assessment of the consequences of disturbed sleep on the cortisol activity. Like urinary cortisol it is unbound, and thus a measure of the biochemically active component of cortisol (Kirschbaum and Hellhammer, 1989). It has a circadian rhythm and a reactivity to stressors that correlates with serum and plasma cortisol (Kirschbaum and Hellhammer, 1994). The morning awakening cortisol response (over the first 30–45 min) is an especially reliable marker of hypothalamus–pituitary–adrenal axis (HPA) activity (Pruessner et al., 1997) that in turn is dependent on a moderate genetic influence and on stressful events preceding the sample collection (Pruessner et al., 1999, Wust et al., 2000).
Rounding up, the collection of salivary cortisol allows for an assessment of HPA activity while at the same time circumventing some of the methodological problems associated with cortisol assessment in the urine and the blood. It allows cortisol activity to be assessed immediately before and after sleep in the natural home environment and for a longer time period. We therefore used this technique in a controlled design in order to study the cortisol activity immediately before and after sleep in patients meeting the DSM-IV criteria of primary insomnia. Furthermore, we wanted to explore whether the changes in cortisol secretion are related to the typical complaints associated with sleep impairment.
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Subjects
Fourteen patients with primary insomnia and 15 healthy controls between 32 and 62 years of age participated (see Table 1). Patients were recruited from the outpatient sleep disorders clinic of the Department of Psychiatry and Psychotherapy of the University of Luebeck. Controls were recruited using advertisements. All subjects were non-smokers and had a body mass index in the normal range between 19 and 25. They went to bed at a certain time regularly and were not shift workers. None of the
Statistical analysis
The means of the cortisol values of each measurement point were calculated for each participant over the whole week of measurement. The inter-day variations of salivary cortisol were evaluated by correlation analyses. Group differences for the salivary cortisol values were analyzed using ANOVAs with repeated measurements and t-tests wherever the ANOVAs revealed a significant effect. For calculating the average bedtime and time of awakening, time points were converted into decimal figures,
Sample statistics
Patients and controls did not differ with regard to age, sex, body mass index, time of awakening or bedtime (see Table 1).
Salivary cortisol profiles of insomnia patients and controls
The ANOVA for the 1-week salivary cortisol measurement showed a significant sampling time as well as a significant sampling time×group interaction effect (time effect: F=133.1, df=2, p=0.000; interaction effect: F=3.45, df=3, p=0.047). Post-hoc t-tests revealed a significantly decreased cortisol level after awakening (T1) for the primary insomnia patients in comparison with
Discussion
The data from this study show that subjects with a higher frequency of nightly awakenings, a low rating of sleep quality, and with the impression of a lack of recovery after awakening have lower awakening cortisol values. Furthermore, similar correlations of the awakening cortisol value with the PSQI, focusing on sleep-related thoughts, and rumination in bed were found. All these results therefore show that a higher disturbance of sleep is associated with a lower cortisol level directly after
Acknowledgements
This study was supported by a grant from the Deutsche Forschungs Gesellschaft (DFG) to J.B. and K.J. (BA 2022/2). We thank Jolanta Chwalko, Andrea Schlagelambers and Michael Andrew for study assistance as well as Prof. Jan Born, in whose laboratory the salivary cortisol salivettes were analyzed.
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