Elsevier

Psychoneuroendocrinology

Volume 101, March 2019, Pages 35-41
Psychoneuroendocrinology

Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate

https://doi.org/10.1016/j.psyneuen.2018.10.015Get rights and content

Highlights

  • Healthy men completed either the Trier Social Stress Test or a Placebo-TSST.

  • High discrimination between two groups was shown in salivary cortisone.

  • Salivary cortisone was associated with state anxiety level and heart rate.

  • Discriminatory power of stress markers was dependent on the time from stress onset.

Abstract

Background

Stress activates the central nervous, the autonomic nervous, and the endocrine system. This study aimed to (1) test the usability of salivary cortisone in a standardized psychosocial stressor, (2) create a comprehensive profile of hormonal responses to determine laboratory parameters with high discriminatory power, and (3) analyze their association with psychometric and autonomic stress measures.

Methods

Healthy young men (18–35 years) completed either the Trier Social Stress Test (TSST) (n = 33) or a Placebo-TSST (n = 34). Blood and saliva were collected at 14 time points along with state-anxiety (STAI) and heart rate. Serum steroids (cortisol*, cortisone*, dehydroepiandrosterone-sulfate, androstenedione*, progesterone*, 17-hydroxyprogesterone*, testosterone, estradiol*, aldosterone*), salivary cortisol* and cortisone*, copeptin*, adrenocorticoptropic hormone*, corticosteroid-binding globulin, and salivary alpha-amylase* were analyzed. We used mixed-design ANOVAs to test group differences, receiver operator characteristic (ROC) curve analyses to assess the discriminatory power of each measure, and Spearman correlation analyses to probe the association between measures.

Results

The largest area under the ROC curve was observed in salivary cortisone at 20 min after the end of the TSST (AUC = 0.909 ± 0.044, p < 0.0001). Significant time-by-group interactions were found in the parameters marked with * above, indicating stress-induced increases. The peak response of salivary cortisone was significantly associated with those of STAI (rho = 0.477, p = 0.016) and heart rate (rho = 0.699, p < 0.0001) in the TSST group.

Conclusion

Our study found salivary cortisone to be a stress biomarker with high discriminatory power and significant correlations with subjective and autonomic stress measures. Our results can inform future stress studies of sampling time for different laboratory parameters.

Introduction

An adaptive response to a stressor (i.e., a demand or threat) comprises activation in the central nervous system, the autonomic nervous system (ANS), and the endocrine system (Chrousos and Gold, 1992). The brain orchestrates the stress response and is central for the adaptation to current and future stressors (Ulrich-Lai and Herman, 2009). ANS stimulation is marked by a rapid increase of heart rate (Allen et al., 2014), the release of plasma catecholamines and salivary alpha-amylase (Granger et al., 2007; Rohleder and Nater, 2009). The response of the hypothalamus-pituitary-adrenal (HPA)-axis, key element of the endocrine stress response, consists of a cascade of hormone releases (Spanakis et al., 2016): corticotropin-releasing hormone (CRH) and copeptin from the hypothalamus (Katan et al., 2008; Urwyler et al., 2015), adrenocorticotropic hormone (ACTH) from the pituitary, and – the primary stress hormone – cortisol from the adrenal glands. More than 90% of the cortisol in circulation is bound to proteins (Lewis et al., 2005). The unbound fraction of cortisol is biologically active and can diffuse into the saliva (Hellhammer et al., 2009). Therefore, salivary cortisol has been used as a surrogate marker of serum free cortisol with its advantage of non-invasive sample collection. However, salivary cortisol is converted to cortisone rapidly and irreversibly, as the salivary glands exhibit high levels of 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) (Blair et al., 2017). In consequence, the concentration of cortisone in saliva is 2–6 times higher than that of cortisol in saliva (Bae et al., 2016). Recently, salivary cortisone was found to be a better surrogate marker of serum free cortisol than salivary cortisol, particularly when serum cortisol levels are low, or when hydrocortisone was administered as a therapeutic or experimental intervention (Blair et al., 2017; Debono et al., 2016; Perogamvros et al., 2010). Therefore, the first aim of our study was to investigate the usability of saliva cortisone as an endocrine stress marker in a standardized psychophysiological stress experiment, the Trier Social Stress Test (TSST) (Kirschbaum et al., 1993).

The second aim of our study was based on the observation that previous stress studies show a high degree of heterogeneity in terms of sampling time points and laboratory parameters. This makes their comparison difficult and can only insufficiently inform future stress studies. We, therefore, wanted to create a comprehensive response profile of laboratory parameters for a standardized psychosocial stressor, the TSST, in healthy young men(Kirschbaum et al., 1993) and a closely matching control task (Het et al., 2009). With a relatively high sampling frequency, we aimed to assess the time courses of measures from different stress axes before, during, and after the intervention and to determine the laboratory parameters which discriminate between the stress and the control group. In addition to the main stress axes (i.e., ANS and the HPA-axis), we investigated how stress affects the level of sex steroid hormones, considering that both chronic stress and the alteration of sex steroid hormones are related to a variety of medical conditions (Byun et al., 2013; Corona and Maggi, 2010; Toufexis et al., 2014).

After identifying laboratory parameters with high discriminatory power, we also assessed their association with other stress measures; specifically, self-reported subjective negative affect (using the state-trait anxiety inventory, STAI (Spielberger et al., 1983)) and heart rate as autonomic stress marker.

Section snippets

Participants

Male participants (n = 67, age range: 18–35 years) were recruited at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany. Exclusion criteria were: smoking, drug or excessive alcohol consumption, university degree in psychology or currently studying psychology, regular medication intake including steroid use, history of cardiovascular or neurological diseases, or a BMI higher than 27. Since magnetic resonance imaging (MRI) was used to acquire brain data for a

Results

There was no significant difference between the stress group (n = 25) and the control group (n = 25) in age or in BMI (Table 1).

Discussion

We find that salivary cortisone can serve as a stress marker in experimental studies. It exhibits high discriminatory power and correlates significantly with subjective and autonomic stress markers such as state anxiety and heart rate. Furthermore, we have identified the time courses and the discriminatory power of a comprehensive set of laboratory parameters, which may inform future studies about when and which laboratory parameter to collect.

Salivary cortisone has recently emerged as a

Conflicts of interest

None.

Acknowledgments

We thank Kathleen Fell and Annette Drechsler for their contribution in the facilitation of the biochemical analyses. Special thanks to Dr. Michael Wakileh for his advice and English proof-reading.

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