Review
Human hypothalamus–pituitary–adrenal axis responses to acute psychosocial stress in laboratory settings

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Abstract

Cumulative acute psychosocial stress is thought to promote the development of a range of disorders which suggests that biomarkers for the physiological response may become valuable tools for biomedical research and development. The search for these biomarkers has been aided by the development of a standardised protocol for inducing psychosocial stress that combines social-evaluative threat and uncontrollability, i.e., the Trier Social Stress Test (TSST). Among other biological markers of acute stress, this test induces significant changes of the hypothalamus–pituitary–adrenal axis (HPAA), which is thought to play a pivotal role in the generation of stress-associated pathologies. The HPAA responses show differences between patients and healthy subjects as well as between pathologies. Moreover, gender, age, personality traits, social environment, and genotype can also shape the individual's acute stress response triggered by the TSST. Characterization of the roles and interactions of these factors in generating a dysregulation of the neuroendocrine responses to acute psychosocial stress await longitudinal studies.

Introduction

Biomarkers of psychosocial stress include components and substrates of the physiological systems that transduce stress. Psychosocial stress and the allostatic load compensating the stressful stimuli have been implicated in psychopathologies such as depression (Parker et al., 2003), the metabolic syndrome (Chrousos, 2000), and systemic hypertension (Esler et al., 2008). As the most important putative biomarkers of psychosocial stress, response parameters of the hypothalamus–pituitary–adrenal axis (HPAA) and the sympathetic nervous system (SNS) are of focal importance to link the individual stress response to health and disease (Chrousos, 2009, McEwen, 1998; Fig. 1).

In search of reliable biomarkers of psychosocial stress and individual factors modulating the stress response magnitude or kinetic, numerous laboratory tasks have been devised for studies under controlled conditions. Among those protocols, the cold pressure test, the Stroop test, public speaking, and other tasks have been employed with varying and sometimes disappointing results. With the introduction of the “Trier Social Stress Test” (TSST, Kirschbaum et al., 1993), a laboratory protocol has become available for a reliable stimulation of biomarkers of psychosocial stress (Dickerson and Kemeny, 2004). The TSST has been widely used to demonstrate both individual differences in the response to psychosocial stress and the dysregulation of that response in several diseases (Hellhammer et al., 2009). Due to limited space, we will focus on studies that have employed the TSST for stimulation of HPAA and discuss the role of various mediators of the acute stress response to psychosocial stress in the present review.

Section snippets

The Trier Social Stress Test (TSST)

The TSST is a standardised motivated performance task protocol that combines high levels of social-evaluative threat and uncontrollability (Dickerson and Kemeny, 2004). The TSST is a task consisting of a brief preparation period followed by a test period in which the subject is required to deliver a free speech concerning their suitability for employment in a mock job interview and to perform mental arithmetic in front of an audience that is trained to withhold verbal and non-verbal feedback (

Cortisol responses to acute psychosocial stress—sources of variation

The best characterized HPAA marker for the response to acute psychosocial stress is the release of cortisol. Measured in blood or saliva, cortisol levels gradually increase within a few minutes (usually less than 10 min) after stimulation onset and reach peak concentrations 10–30 min after stress cessation. Although reliably detected in groups of healthy individuals and patients alike, the cortisol response to acute psychosocial stress shows considerable variation between individuals. These

Habituation—changing the cortisol response pattern with experience

Prior experience of psychosocial stress modulates subsequent HPAA responses to the TSST. Normally the salivary cortisol response to the TSST habituates over repeated exposures (Pruessner et al., 1997) while in subjects suffering from chronic exhaustion the response increases, suggesting an enhanced vulnerability to psychosocial stress (Kudielka et al., 2006). Obese women with a high waist to hip ratio showed an amplified cortisol response to psychosocial stress in the TSST while lean women with

Concluding remarks

The biological response to acute psychosocial stress has been best characterized using changes in cortisol levels as a marker of distressing challenge. Several demographic, physiological, and biological variables have been found to moderate the magnitude of the individual cortisol stress response. These factors explain to a great extent the variability observed between individual responses to acute stress documented over the past 25 years.

Unfortunately, however, there is still a significant

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