Cited by 1,481Stress Responses and CortisolAdrenal Hormones and DisordersMedicinal Plants and Bioactive Compounds

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Stress and the General Adaptation Syndrome

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Selye, H.·1950·BMJ

DOI 10.1136/bmj.1.4667.1383PMC PMC2038162

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Abstract

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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Background
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Durieux, L., Herbeaux, K., Borcuk, C., Hildenbrand, C., Andry, V., Goumon, Y., Barbelivien, A., Mathis, C., Bataglia, D., Majchrzak, M. J., et al. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15803 · Cited by 15
“The engagement of the Ins_C makes perfect sense as the autonomic response facing stress is crucial to allow efficient coping (de Kloet et al., 1998; Selye, 1950).”
BackgroundInfluential
Under pressure: the interaction between high-stakes contexts and individual differences in decision-making in humans and non-human species
Sosnowski, M. J., & Brosnan, S. F. (2023) · Animal Cognition · doi:10.1007/s10071-023-01768-z · Cited by 24
“One key hormone in the HPA response is cortisol, a metabolic steroid hormone that has been widely studied in the context of stress in both human subjects and other animals (Selye 1950; Sapolsky 1988; Sapolsky et al. 2000).”
BackgroundInfluential
The Influence of Stress on Student Performance during Simulation-Based Learning: A Pilot Randomized Trial
Cavaleri, R., Withington, A., Chalmers, J., & Blackstock, F. C. (2023) · ATS Scholar · doi:10.34197/ats-scholar.2022-0042oc · Cited by 16
“The processes out-lined by the general adaptation syndrome may explain the relationship between complexity of the SBE and the level of anxiety experienced (24).”
Background
Occupational Stress and Burnout
Jacobs, C. M. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.1003104 · Cited by 16
Validity of mental and physical stress models
Hendry, E., McCallister, B., Elman, D. J., Freeman, R. L., Borsook, D., & Elman, I. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105566 · Cited by 18
Role and Status of Biomarkers in Technostress Research: A Systematic Review
Mishra, P. K., & Rašticová, M. (2024) · Psychology Research and Behavior Management · doi:10.2147/prbm.s446782 · Cited by 16
Selective Rapid Eye Movement Sleep Deprivation Affects Cell Size and Number in Kitten Locus Coeruleus
Shaffery, J., Allard, J. S., Manaye, K., & Roffwarg, H. (2012) · Front. Neur. · doi:10.3389/fneur.2012.00069 · Cited by 16
“Single factor ANOVA (p 0.05) determined group differences in final body weight and in the weights of the individual organs across the groups (Selye, 1936, 1950).”
MethodInfluential
Reliability and Validity of the Work and Well-Being Inventory (WBI) for Employees
Vendrig, A. A., & Schaafsma, F. G. (2017) · Journal of Occupational Rehabilitation · doi:10.1007/s10926-017-9729-7 · Cited by 18
“Main theory: general adaption syndrome (GAS) [42]”
Single oral administration of flavan 3-ols induces stress responses monitored with stress hormone elevations in the plasma and paraventricular nucleus
Fujii, Y., Suzuki, K., Hasegawa, Y., Nanba, F., Toda, T., Adachi, T., Taira, S., & Osakabe, N. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.06.015 · Cited by 16
Neuroendocrinological treatment targets for posttraumatic stress disorder
Yoon, S., & Kim, Y. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.11.021 · Cited by 19
“Following exposure to stress, a physiologic response arises to improve the chances for achieving homeostasis and survival (Goldstein and Kopin, 2007; Selye, 1950).”
Neurobiology of Aggressive Behavior—Role of Autoantibodies Reactive With Stress-Related Peptide Hormones
Værøy, H., Schneider, F., & Fetissov, S. O. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00872 · Cited by 16
“In his theory of the general adaptation syndrome, Hans Selye emphasized the role of the immune system following the response to stress (6).”
Background
Heat adaptation in humans: the significance of controlled and regulated variables for experimental design and interpretation
Taylor, N. A. S., Notley, S. R., & Lindinger, M. I. (2020) · European Journal of Applied Physiology · doi:10.1007/s00421-020-04489-0 · Cited by 16
“All of those variables must interact with the genetic, phenotypic and situational status of each individual (Selye 1950; Adolph 1956, 1964).”
Background
Massagem e Reiki para redução de estresse e melhoria de qualidade de vida: ensaio clínico randomizado
Kurebayashi, L. F. S., Gnatta, J. R., Kuba, G., Giaponesi, A. L. L., de Souza, T. P. B., & Turrini, R. N. T. (2020) · Revista da Escola de Enfermagem da USP · doi:10.1590/s1980-220x2018059103612 · Cited by 16
Cognitive reserve and coping strategies predict the level of perceived stress during COVID-19 pandemic: A cross-sectional study
Panico, F., Luciano, S. M., Sagliano, L., Santangelo, G., & Trojano, L. (2022) · Personality and Individual Differences · doi:10.1016/j.paid.2022.111703 · Cited by 17
“In future studies it would be worth investigating how coping strategies and CR modulate perceived stress after prolonged stressful events such as the post-traumatic stress disorder, which might lie in what Selye (1950) described as an ‘exhaustion stage’.”
Influential
Deployment Stressors : A Review of the Literature and Implications for Members of the Canadian Armed Forces
Watkins, K. (2014) · Cited by 16
Proposal for a Four-Phase Stress Model
Lipp, M. E. N., & Lipp, L. M. N. (2019) · Psychology · doi:10.4236/psych.2019.1011094 · Cited by 16
“The idea that the stress process consists of four phases instead of the three proposed by Selye (1950), was again evaluated in a recent study, in which a database comprising 37,454 participants was used.”
BackgroundInfluential
Energy metabolism in largemouth bass (Micropterus floridanus salmowes) from stressed and non-stressed environments: Adaptations in the secondary stress response
Dehn, P. F., & Schirf, V. R. (1986) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(86)90360-9 · Cited by 16
Acute Myelogenous Leukemia: Current Status of Therapy in Adults
Foon, K. A., & Gale, R. P. (1984) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-82249-0_9 · Cited by 16
Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition
Petitjeans, F., Géloën, A., Pichot, C., Leroy, S., GHIGNONE, M., & Quintin, L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194569 · Cited by 17
Dynamic Measures of Team Adaptation
Gorman, J. C., Grimm, D., Robinson, F. E., Winner, J. L., Wiese, C. W., & Roudebush, C. (2025) · Human Factors The Journal of the Human Factors and Ergonomics Society · doi:10.1177/00187208251314262 · Cited by 17
“Reorganization is akin to biological systems in which component systems (e.g., nervous; cardiovascular; and digestive) continuously alter their joint behavior in coordinated ways allowing organisms to adapt to and survive internal and external stressors (Selye, 1950).”
Possible association between phantom vibration syndrome and occupational burnout
Lin, Chen, C.-P., Wu, C.-C., & Chang, L. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s73038 · Cited by 16
Airman and Family Resilience: Lessons from the Scientific Literature
Meadows, S. O., Miller, L. L., & Robson, S. M. (2016) · Rand health quarterly · doi:10.7249/rhq-05-03-10 · Cited by 15
Nutraceuticals as Adaptogens
Gulati, K., Anand, R., & Ray, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802147-7.00016-4 · Cited by 19
Correlates of psychological distress in epileptic patients during the COVID-19 outbreak
Giordano, A., Siciliano, M., Micco, R. D., Sant’Elia, V., Russo, A., Tedeschi, G., & Tessitore, A. (2020) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2020.107632 · Cited by 15
Evaluating the Challenges and Reproducibility of Studies Investigating DNA Methylation Signatures of Psychological Stress
Zhang, Y., & Liu, C. (2022) · Epigenomics · doi:10.2217/epi-2021-0190 · Cited by 20
Hepatitis B Virus-Associated Hepatocellular Carcinoma and Chronic Stress
Noverati, N., Hamidu, R. B., Halegoua-DeMarzio, D. L., & HANN, H.-W. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073917 · Cited by 15

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
DOI: 10.1136/bmj.1.4667.1383
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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Stress and the General Adaptation Syndrome

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