Human models in acute and chronic stress: Assessing determinants of individual hypothalamus–pituitary–adrenal axis activity and reactivity

Stress is one of the most significant health problems in modern societies and the 21st century. This explains a pressing need for investigations into the biological pathways linking stress and health. Besides the locus coeruleus–noradrenaline/autonomic (sympathetic) nervous system (), the hypothalamus–pituitary–adrenal (HPA) axis is the major physiological stress response system in the body. Since alterations in HPA axis regulation under basal conditions and in response to acute stress appear to be a close correlate or even a determining factor of the onset of different diseases or disease progression (; ; ; ; ; ; ), the characterization of an individual's HPA axis activity as well as reactivity pattern to psychosocial stress appears to be of major interest. It is obvious that such a research agenda substantially depends on the availability of appropriate measures. However, since the HPA axis is a highly adaptive system which is characterized by marked inter- and intraindividual variability (; ), the development of such markers of HPA axis regulation in humans was—and still is—a rather challenging task. In this brief review, we focus on findings on two HPA axis measures, namely the cortisol-awakening response (CAR) to assess HPA axis basal activity and the Trier social stress test (TSST) to investigate HPA axis stress reactivity.