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Stress and the General Adaptation Syndrome
Open accessAbstract
With the concept of the general adaptation syndrome we have attempted to integrate a number of seemingly quite unrelated observations into a single unified biologic system.I would draw attention briefly to the work of Claude Bernard, who showed how important it is to maintain the constancy of the "milieu interieur" ; Cannon's concept of " homoeostasis "; Frank Hartmann's " general tissue hor- mone" theory of the corticoids; Dustin's observations on the " caryoclastic poisons," the " post-operative disease," the curative action of fever, foreign proteins, and of other " non-specific therapeutic agents "; the " nephrotoxic sera " of Masugi; and to the " Goldblatt clamp" for the production of experimental renal hypertension.At first sight it would seem that all these observations have little in common and that there is no reason to attempt their integration into a unified system of physio- logical and pathological events.Yet most of my research work has been devoted to the construction of bridges between these and many additional facts, since they were thought to be interconnected in nature.Through the com- prehension of their unity we hoped to learn how to use them better for the understanding of life and the treatment of disease.The keynote of this unification was the tenet that all living organisms can respond to stress as such, and thiat in this respect the basic reaction pattern is always the same, irrespective of the agent used to produce stress.We called this response the general adaptation syndrome, and its derailments the diseases of adaptation.Anything that causes stress endangers life, unless it is met by adequate adaptive responses; conversely, anything that endangers life causes stress and adaptive responses.Adaptability and resistance to stress are fundamental pre- requisites for life, and every vital organ and function par- ticipates in them.In order to present a well-proportioned outline of the general adaptation syndrome it was necessary, therefore, to peruse every branch of physiology, biochemis- try, pathological anatomy, and clinical medicine in search of the "stress factor" in all aspects of normal and abnormal life.It will take many years, indeed many generations, before the details of the general adaptation syndrome are satis- *The first part of the Heberden Oration, given on June 2, 1950.
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“An updated version [10] of the classic general adaptation syndrome [152] and the foundational stress response theory of Horowitz [72], may provide a potential conceptual framework by postulating that stress reactions proceed through four hierarchical phases: freeze, flight, fight, and faint (or tonic immobility).”
From Complex PTSD and borderline personality disorder (2021) · cites this paper as [152]
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Influence of Physical Activity and Nutrition on Obesity‐Related Immune Function
Huang, C., Zourdos, M. C., Jo, E., & Ormsbee, M. J. (2013) · The Scientific World JOURNAL · doi:10.1155/2013/752071 · Cited by 60
“This initial fatigue in response to a new stimulus is described in Hans Seyle’s landmark work, the general adaptations syndrome (GAS) [74], as the “alarm reaction stage.”
BackgroundInfluentialFactors promoting vulnerability to dysregulated stress reactivity and stress‐related disease
Russell, A. L., Tasker, J. G., Lucion, A. B., Fiedler, J. L., Munhoz, C. D., Wu, T. J., & Deak, T. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12641 · Cited by 66
Spiro, H. M. (1983) · New England Journal of Medicine · doi:10.1056/nejm198307073090110 · Cited by 59
Cellular Stress and General Pathological Processes
Gusev, E. Y., & Zotova, N. V. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190319114641 · Cited by 64
Beta Activities in EEG Associated with Emotional Stress
Hayashi, T., Okamoto, E., Nishimura, H., Mizuno‐Matsumoto, Y., Ishii, R., & Ukai, S. (2009) · International Journal of Intelligent Computing in Medical Sciences & Image Processing · doi:10.1080/1931308x.2009.10644171 · Cited by 58
Effects of acute heat stress at different ambient temperature on hepatic redox status in broilers
Miao, Q., Si, X., Xie, Y., Chen, L., Liu, Z., Liu, L., Tang, X., & Zhang, H. (2020) · Poultry Science · doi:10.1016/j.psj.2020.05.019 · Cited by 61
“receive environmental stimulation: alarm, resistance, and exhaustion (Selye, 1950; Mcewen, 2005).”
BackgroundHosseini‐Kamkar, N., Lowe, C. J., & Morton, J. B. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.04.006 · Cited by 62
Daskalakis, N. P., Meijer, O. C., & de Kloet, E. R. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100455 · Cited by 64
“pothesis’ by which the action of antagonistic adaptive hormones (proinflammatory mineralocorticoids and anti-inflammatory glucocorticoids) can set disease susceptibility at different levels (Selye, 1950).”
The discovery and early use of cortisone
Glyn, J. H. (1998) · Journal of the Royal Society of Medicine · doi:10.1177/014107689809101004 · Cited by 57
Stressing the obvious? An allostatic look at critical illness
Brame, A., & Singer, M. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181f23e92 · Cited by 56
“He later showed that any acute nonspecific noxious insult, such as exposure to cold, surgical injury, spinal shock by cord transection, excessive muscular exercise, and administration of various pharmacologic agents could reproduce this syndrome (23).”
BackgroundEsmaeili, N., Kenari, A. A., & Rombenso, A. (2017) · Comparative Clinical Pathology · doi:10.1007/s00580-017-2457-8 · Cited by 57
“When the active uptake of ions is disorganized, hyperchloremia in fish is known to occur (Larsson et al. 1985; Selye 1950).”
BackgroundTen questions concerning the impact of environmental stress on office workers
Awada, M., Becerik-Gerber, B., Liu, R., Seyedrezaei, M., Lu, Z., Xenakis, M., Lucas, G., Roll, S. C., & Narayanan, S. S. (2022) · Building and Environment · doi:10.1016/j.buildenv.2022.109964 · Cited by 60
“The GAS model explains how the human body reacts and adapts to stressors [19].”
BackgroundDivergent regulation of distinct glucocorticoid systems in alcohol dependence
Edwards, S., Little, H. J., Richardson, H. N., & Vendruscolo, L. F. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.04.004 · Cited by 56
“However, even Selye observed what he termed a “general adaptive syndrome” and “diseases of adaptation” (Selye, 1950).”
Management of stress in inflammatory bowel disease: a therapeutic option?
Goodhand, J., Wahed, M., & Rampton, D. S. (2009) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.09.55 · Cited by 58
Cooperativity and complementarity: Synergies in non-classical and classical glucocorticoid signaling
Samarasinghe, R. A., Witchell, S. F., & DeFranco, D. B. (2012) · Cell Cycle · doi:10.4161/cc.21018 · Cited by 54
Metadata
- Authors
- Selye, H.
- Affiliations
- Université de Montréal (CA)
- Corresponding author
- Selye, H.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 1950-06-17
- Volume
- 1
- Issue
- 4667
- Pages
- 1383-1392
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC2038162
- OpenAlex
- W1991680271
- Cited by
- 1,481
- References
- 0
- Citations by year
- 2026: 59 · 2025: 98 · 2024: 79 · 2023: 111 · 2022: 117 · 2021: 96 · 2020: 102 · 2019: 90 · 2018: 80 · 2017: 64 · 2016: 64 · 2015: 47 · 2014: 54 · 2013: 51 · 2012: 52
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Bioactive Compounds
- Keywords
- general adaptation syndrome, stress, stress response, homeostasis, milieu intérieur, corticosteroids, tissue hormones, fever, nonspecific therapy, experimental renal hypertension, adaptability
- MeSH terms
- Acclimatization, Adaptation, Physiological, Adrenal Cortex, Adrenocorticotropic Hormone, General Adaptation Syndrome, Stress, Physiological, Tissue Extracts
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