Human models in acute and chronic stress: Assessing determinants of individual hypothalamus–pituitary–adrenal axis activity and reactivity
Open accessAbstract
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 ( Chrousos and Gold 1992 ), 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 ( Holsboer 1989 ; Chrousos and Gold 1992 ; Tsigos and Chrousos 1994, 2002 ; Stratakis and Chrousos 1995 ; McEwen 1998 ; Heim et al. 2000a ; Raison and Miller 2003 ), 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 ( Mason 1968 ; Hellhammer et al. 2009 ), 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.
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The cortisol-awakening response (CAR) is characterized by elevated cortisol levels in the morning.
“The cortisol-awakening response (CAR) is characterized by elevated cortisol levels in the morning, as noted in Kudielka and W¨ ust (2010).”
From Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency (2026) · cites this paper as Kudielka and Wüst (2010)
In a healthy individual, cortisol levels vary throughout the day in response to the circadian rhythm.
“In a healthy individual, cortisol levels vary throughout the day in response to the circadian rhythm.”
From Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency (2026) · cites this paper as Kudielka and Wüst (2010)
Cites
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · see citing works
Dickerson, S. S., & Kemeny, M. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.3.355 · Cited by 5,881 · see citing works
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
Tsigos, C., & Chrousos, G. P. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00429-4 · Cited by 2,822 · see citing works
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968 · see citing works
Kirschbaum, C., Kudielka, B. M., Gaab, J., Schommer, N. C., & Hellhammer, D. H. (1999) · Psychosomatic Medicine · doi:10.1097/00006842-199903000-00006 · Cited by 1,890 · cited 4× · see citing works
“To evaluate the maximum capacity of the adrenal cortex, a standard ACTH1–24 (250mg) test should be applied (Kirschbaum et al. 1999).”
BackgroundMethodInfluentialSelf-citationDepression and cortisol responses to psychological stress: A meta-analysis
Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.02.010 · Cited by 1,194 · see citing works
Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines
Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H.-M., Follett, H., Kales, A., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031562 · Cited by 1,050 · see citing works
The effects of sex and hormonal status on the physiological response to acute psychosocial stress
Kajantie, E., & Phillips, D. I. W. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.07.002 · Cited by 1,035 · see citing works
Kudielka, B. M., Hellhammer, D. H., & Wüst, S. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.10.004 · Cited by 963 · see citing works
Self-citationThe awakening cortisol response: methodological issues and significance
Clow, A., Thorn, L., Evans, P., & Hucklebridge, F. (2004) · Stress · doi:10.1080/10253890410001667205 · Cited by 856 · see citing works
Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis
Buske-Kirschbaum, A., Jobst, S., Wustmans, A., Kirschbaum, C., Rauh, W., & Hellhammer, D. (1997) · Psychosomatic Medicine · doi:10.1097/00006842-199707000-00012 · Cited by 696 · see citing works
Steptoe, A., Owen, N., Kunz-Ebrecht, S. R., & Brydon, L. (2004) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00086-6 · Cited by 620 · cited 2× · see citing works
“It was reported that the CAR is positively associated with the amount of perceived chronic stress (Schulz et al. 1998; Pruessner et al. 1999; Wüst et al. 2000b; Schlotz et al. 2004; Alderling et al. 2006; Hurwitz Eller et al. 2006) and perceived loneliness (Steptoe et al. 2004b).”
BackgroundHellhammer, J., Fries, E., Schweisthal, O. W., Schlotz, W., Stone, A. A., & Hagemann, D. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.10.005 · Cited by 540 · see citing works
Neuroendocrinology and pathophysiology of the stress system
STRATAKIS, C. A., & CHROUSOS, G. P. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44666.x · Cited by 533 · see citing works
Is the cortisol awakening rise a response to awakening?
Wilhelm, I., Born, J., Kudielka, B. M., Schlotz, W., & Wüst, S. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.01.008 · Cited by 454 · see citing works
Self-citationSchlotz, W., Hellhammer, J., Schulz, P., & Stone, A. A. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000116715.78238.56 · Cited by 418 · see citing works
Rohleder, N., Joksimovic, L., Wolf, J. M., & Kirschbaum, C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.11.018 · Cited by 393 · see citing works
Schmidt-Reinwald, A., Pruessner, J. C., Hellhammer, D. H., Federenko, I., Rohleder, N., Schürmeyer, T. H., & Kirschbaum, C. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00103-4 · Cited by 367 · see citing works
The relationship between smoking status and cortisol secretion.
Badrick, E., Kirschbaum, C., & Kumari, M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2155 · Cited by 284 · see citing works
Roelofs, K., van Peer, J., Berretty, E., Jong, P. D., Spinhoven, P., & Elzinga, B. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.022 · Cited by 236 · see citing works
Circadian regulation of cortisol after hippocampal damage in humans
Buchanan, T. W., Kern, S., Allen, J. S., Tranel, D., & Kirschbaum, C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.014 · Cited by 206 · see citing works
(2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.03.005 · Cited by 200 · cited 2× · see citing works
“In different psychological stress experiments, evidence for com- bined stimulatory effects of caffeine and psychologi- cal stress on HPA axis responses were reported (Lane et al. 1990; al’Absi et al. 1998; Lovallo et al. 2006).”
BackgroundFree cortisol awakening responses are influenced by awakening time
Federenko, I., Wüst, S., Hellhammer, D. H., Dechoux, R., Kumsta, R., & Kirschbaum, C. (2004) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00021-0 · Cited by 173 · cited 6× · see citing works
“higher CAR compared to late awakeners (Edwards et al. 2001b; Kudielka and Kirschbaum 2003; Federenko et al. 2004a; Williams et al. 2005; Kudielka et al. 2007b).”
BackgroundMethodInfluentialSelf-citationDelayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men
von Känel, R., Kudielka, B. M., Preckel, D., Hanebuth, D., & Fischer, J. E. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.03.013 · Cited by 158 · see citing works
Self-citationBehavioral problems in dementia patients and salivary cortisol patterns in caregivers
de Vugt, M. E., Nicolson, N. A., Aalten, P., Lousberg, R., Jolle, J., & Verhey, F. R. J. (2005) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.17.2.201 · Cited by 136 · see citing works
Kudielka, B. M., Schmidt-Reinwald, A. K., Hellhammer, D. H., & Kirschbaum, C. (1999) · Neuroendocrinology · doi:10.1159/000054504 · Cited by 135 · cited 2× · see citing works
“With respect to age, we did not observe any age effects in salivary cortisol responses to the TSST in healthy younger compared to older women (Kudielka et al. 1999).”
BackgroundSelf-citationBrody, S., Preut, R., Schommer, K., & Schürmeyer, T. H. (2002) · Psychopharmacology · doi:10.1007/s00213-001-0929-6 · Cited by 127 · see citing works
Cortisol responses to psychological stress and correlations with personality traits
Kirschbaum, C., Bartussek, D., & Strasburger, C. J. (1992) · Personality and Individual Differences · doi:10.1016/0191-8869(92)90181-n · Cited by 115 · see citing works
Mommersteeg, P. M. C., Heijnen, C. J., Verbraak, M. J. P. M., & van Doornen, L. J. P. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.07.003 · Cited by 111 · see citing works
Wiesli, P., Schmid, C., Kerwer, O., Nigg-Koch, C., Klaghofer, R., Seifert, B., Spinas, G. A., & Schwegler, K. (2005) · Diabetes Care · doi:10.2337/diacare.28.8.1910 · Cited by 88 · see citing works
Edwards, S., Hucklebridge, F., Clow, A., & Evans, P. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000033123.70631.8e · Cited by 79 · see citing works
Effects of nutrition on neuro-endocrine stress responses
Rohleder, N., & Kirschbaum, C. (2007) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3281e38808 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biological and psychological markers of stress in humans: Focus on the Trier Social Stress Test
Allen, A. P., Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.005 · Cited by 734 · see citing works
Investigation of Cortisol Dynamics in Human Sweat Using a Graphene-Based Wireless mHealth System
Torrente-Rodríguez, R. M., Tu, J., Yang, Y., Min, J., Wang, M., Song, Y., Yu, Y., Xu, C., Ye, C., IsHak, W. W., et al. (2020) · Matter · doi:10.1016/j.matt.2020.01.021 · Cited by 479 · see citing works
The psychoneuroimmunological effects of music: A systematic review and a new model
Fancourt, D., Ockelford, A., & Belai, A. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.10.014 · Cited by 316 · see citing works
Pruessner, M., Cullen, A. E., Aas, M., & Walker, E. F. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.013 · Cited by 315 · see citing works
Yan, J., Pan, Y., Cai, W., Cheng, Q., Dong, W., & An, T. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s77710 · Cited by 254 · see citing works
Olafsdottir, G., Cloke, P., Schulz, A., van Dyck, Z., Eysteinsson, T., Thorleifsdottir, B., & Vögele, C. (2020) · Environment and Behavior · doi:10.1177/0013916518800798 · Cited by 193 · see citing works
Genetic determinants of aggression and impulsivity in humans
Pavlov, K. A., Chistiakov, D. A., & Chekhonin, V. P. (2012) · Journal of Applied Genetics · doi:10.1007/s13353-011-0069-6 · Cited by 184 · see citing works
The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms
Waltes, R., Chiocchetti, A. G., & Freitag, C. M. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32388 · Cited by 182 · see citing works
Bosch, N. M., Riese, H., Reijneveld, S. A., Bakker, M. P., Verhulst, F. C., Ormel, J., & Oldehinkel, A. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.013 · Cited by 163 · see citing works
Oxytocin, cortisol, and triadic family interactions
Gordon, I., Zagoory-Sharon, O., Leckman, J. F., & Feldman, R. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.08.008 · Cited by 158 · see citing works
Emotional reactivity and internalizing symptoms: Moderating role of emotion regulation
Shapero, B. G., Abramson, L. Y., & Alloy, L. B. (2016) · Cognitive Therapy and Research · doi:10.1007/s10608-015-9722-4 · Cited by 114 · see citing works
The relationship between cortisol responses to laboratory stress and cortisol profiles in daily life
Kidd, T., Carvalho, L. A., & Steptoe, A. (2014) · Biological Psychology · doi:10.1016/j.biopsycho.2014.02.010 · Cited by 88 · see citing works
Huffziger, S., Ebner-Priemer, U., Zamoscik, V., Reinhard, I., Kirsch, P., & Kuehner, C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.04.014 · Cited by 79 · see citing works
Ulmer-Yaniv, A., Avitsur, R., Kanat-Maymon, Y., Schneiderman, I., Zagoory-Sharon, O., & Feldman, R. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.02.017 · Cited by 68 · see citing works
Fischer, S., Duncko, R., Hatch, S. L., Papadopoulos, A., Goodwin, L., Frissa, S., Hotopf, M., & Cleare, A. J. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.11.011 · Cited by 66 · see citing works
Markovic, V. M., Cupic, Z., Vukojevic, V., & Kolar-Anic, L. (2011) · Endocrine Journal · doi:10.1507/endocrj.ej11-0037 · Cited by 54 · see citing works
Duchesne, A., Tessera, E., Dedovic, K., Engert, V., & Pruessner, J. C. (2012) · Biological Psychology · doi:10.1016/j.biopsycho.2011.09.009 · Cited by 56 · see citing works
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Lattova, Z., Keckeis, M., Maurovich-Horvat, E., Wetter, T. C., Wilde-Frenz, J., Schuld, A., & Pollmächer, T. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.03.013 · Cited by 54 · see citing works
Haller, J. (2014) · Current topics in behavioral neurosciences · doi:10.1007/7854_2014_284 · Cited by 47 · see citing works
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Herane-Vives, A., Fischer, S., de Angel, V., Wise, T., Cheung, E., Chua, K.-C., Arnone, D., Young, A. H., & Cleare, A. J. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.10.026 · Cited by 46 · see citing works
Fingernail cortisol – State of research and future directions
Fischer, S., Schumacher, S., Skoluda, N., & Strahler, J. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100855 · Cited by 40 · see citing works
McIntosh, R. C., Ironson, G., Antoni, M., Kumar, M., Fletcher, M. A., & Schneiderman, N. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.10.024 · Cited by 37 · see citing works
al'Absi, M., & Allen, A. M. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.687106 · Cited by 34 · see citing works
Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment
Czamanski-Cohen, J., Sarid, O., Cwikel, J., Douvdevani, A., Levitas, E., Lunenfeld, E., & Har-Vardi, I. (2015) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-015-0581-4 · Cited by 19 · see citing works
Park, S.-H., Sim, Y.-B., Kim, S.-S., Lee, J.-R., Sharma, N., & Suh, H.-W. (2016) · Animal Cells and Systems · doi:10.1080/19768354.2016.1221854 · Cited by 1 · see citing works
Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency
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“The cortisol-awakening response (CAR) is characterized by elevated cortisol levels in the morning, as noted in Kudielka and W¨ust (2010).”
- Authors
- Kudielka, B. M., & Wüst, S.
- Affiliations
- Constructor University (DE)
- Central Institute of Mental Health (DE)
- Corresponding author
- Kudielka, Brigitte M.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2010-01
- Volume
- 13
- Issue
- 1
- Pages
- 1-14
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- OpenAlex
- W2084038751
- Cited by
- 424
- References
- 32
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 20 · 2023: 22 · 2022: 15 · 2021: 31 · 2020: 40 · 2019: 30 · 2018: 22 · 2017: 23 · 2016: 24 · 2015: 29 · 2014: 20 · 2013: 36 · 2012: 36
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GRH 1389/1, WU 324/ 3-, 1389/1)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- hypothalamic-pituitary-adrenal axis, HPA axis reactivity, cortisol awakening response, Trier Social Stress Test, acute stress, chronic stress, psychosocial stress, individual differences, stress biomarkers
- MeSH terms
- Acute Disease, Chronic Disease, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Social Behavior, Stress, Physiological, Stress, Psychological
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