Exhaustion is associated with reduced habituation of free cortisol responses to repeated acute psychosocial stress

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Abstract

We investigated the association between exhaustion and the habituation of free cortisol responses to repeated stress exposure. The study comprised 25 healthy male subjects (38–59 years) who were confronted three times with the Trier Social Stress Test. Mean cortisol responses showed the well-known general habituation effect. A two-way interaction day by exhaustion (p < 0.05) indicated that mean cortisol responses vary across stress sessions depending on the extent of exhaustion. Linear regression revealed a negative dose–response relationship between exhaustion and the degree of habituation (p < 0.02). We identified 19 individuals showing a response habituation (negative slope) and 6 individuals showing a response sensitization over the three sessions (positive slope) with the latter reporting higher exhaustion scores. It might be hypothesized that impaired habituation to repeated exposure to the same stressor could reflect a state of increased vulnerability for allostatic load. Absence of normal habituation might be one potential mechanism how exhaustion relates to increased disease vulnerability.

Introduction

Accumulating evidence from animal (Brodish and Odio, 1989, Akana et al., 1992, Pecoraro et al., 2004) and human data (McEwen and Stellar, 1993, Chrousos, 1995) show that chronic stress can modulate the functioning of the hypothalamus–pituitary–adrenal (HPA) axis. Furthermore, dysregulation of the HPA axis have been associated with onset and course of several psychosomatic and psychiatric disorders (Holsboer, 1989, Chrousos and Gold, 1992, Tsigos and Chrousos, 1994, Björntorp and Rosmond, 1999, Heim et al., 2000, Raison and Miller, 2003). A psychological state that is viewed as a potential consequence of long-term, chronic stress is vital exhaustion (VE). VE is characterized by unusual fatigue, loss of mental and physical energy, increased irritability, and a feeling of demoralization (Appels et al., 1987, Appels and Mulder, 1988). In epidemiological studies, VE has been established as an independent risk factor for coronary artery disease (CAD; Appels et al., 1993, Kop et al., 1994, Koertge et al., 2002). To date, only few studies investigated whether exhaustion affects the responsiveness of the HPA axis to stressful situations. Previous research points to altered HPA axis functioning in exhaustion. Nicolson and van Diest (2000) observed a pattern of lower basal salivary cortisol levels throughout the day, with significant differences in the evening in vitally exhausted subjects versus healthy controls. However, a single exposure to a laboratory speech task did not reveal any differences in cortisol stress responses between groups (Nicolson and van Diest, 2000). Kristenson et al., 1998, Kristenson et al., 2001 compared Lithuanian versus Swedish men in a cross-cultural comparison and found that low peak cortisol responses to a standardized laboratory stress battery were significantly related to vital exhaustion and high baseline cortisol levels. Recently, Dahlgren et al. (2004) reported on higher workload, fatigue, and exhaustion levels in a group of white-collar workers with lowered cortisol levels in a high stress condition.

A hallmark of the adaptive propensity of the human HPA axis stress response is the rapid habituation to repeated exposure to the same stimulus (Levine, 1978, Gunnar et al., 1989, Deinzer et al., 1997, Pruessner et al., 1999, Gerra et al., 2001). An insufficient ability to adjust or habituate to repeated exposure to the same stressor is considered as one of four different scenarios that leads to allostatic load (namely repeated “hits”, lack of adaptation, prolonged response, or inadequate response; McEwen, 1998, McEwen and Seeman, 1999). Allostasis means ‘maintaining stability through change’ (Sterling and Eyer, 1988) and allostatic load is the cumulative long-term effect of the physiological systems’ attempts to adapt to life's demands (McEwen and Stellar, 1993, McEwen, 1998). The proposed allostatic load index consists of at least 10 biological parameters including cortisol (Seeman et al., 1997, Seeman et al., 2001, Schnorpfeil et al., 2003). Failing to habituate – or the loss of allostasis, might lead to a higher susceptibility to disease or declines in physical and cognitive functioning (Seeman et al., 2001, Karlamangla et al., 2002). We hypothesized that exhaustion might impair an individuals’ ability to show habituation. In this analysis, we, therefore, investigated the association between exhaustion as measured by the Maastricht-Vital-Exhaustion-Questionnaire and repeated exposure to acute psychosocial stress using the Trier Social Stress Test (TSST). The TSST is a standardized and validated stress protocol for laboratory settings, which reliably elicits endocrine stress responses in the majority of individuals (Kirschbaum et al., 1993, Dickerson and Kemeny, 2004, Kudielka et al., 2004a). A general habituation effect has been consistently reported for a variety of stress paradigms including the Trier Social Stress Test (Pruessner et al., 1999, Schommer et al., 2003, Federenko et al., 2004, Wüst et al., 2005). In sum, the aim of the present study was to elucidate whether exhaustion attenuates the endocrine stress response habituation to psychosocial stress in healthy adults.

Section snippets

Study design and recruitment of participants

The study protocol was formally approved by the ethics committee of the Federal Institute of Technology (ETH), Zurich, Switzerland. All participants gave written consent.

As part of a large survey on “Work and Health”, the permanent non-faculty employees of the Federal Institute of Technology, older than 35 years were invited to participate in a written health assessment. The questionnaire inquired about the personal and family medical history. It assessed a range of data including demographic

Sample characteristics

As summarized in Table 1, the present study sample held middle to high socioeconomic status and showed favorable health behaviors. Due to the chosen recruitment procedure, all subjects were employees of the ETH aged 38–59 years. VE scores ranged between 0 and 17 with a mean of 6.0 ± 4.5 (S.D.). The majority of the sample (56%) showed mild to moderate exhaustion, while 32% did not report any exhaustion. Three subjects (12%) had exhaustion scores above 10.

Cortisol stress responses, habituation and exhaustion

GLM with repeated measures resulted in: (a)

Discussion

The present study addresses for the first time the question whether exhaustion, a common sequela of chronic distress, affects the habituation of the HPA axis response to repeated acute psychosocial stress. Vital exhaustion was assessed by the Maastricht-Vital-Exhaustion-Questionnaire. VE is characterized by unusual fatigue, loss of energy, sleep disturbance, and irritability and has prospectively been linked to cardiovascular disease (Appels et al., 1993, Kop et al., 1994, Koertge et al., 2002

Acknowledgements

This work was supported by Grant 32-68277 from the Swiss National Science Foundation (SNF) and by the Federal Institute of Technology (ETH), Zurich, Switzerland. Since October 2004, BMK is supported by grants from the German Research Foundation (DFG grant KU1404/4-1).

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