Evolution of the stress concept : Past and Future

1. Evolution of the stress concept : Past and Future

2. The Greeks-“Harmony” “Balance” “Equilibrium” : “steady state” - When threatening forces = counteracting forces put forth to neutralize • Heracleites(540-480 BC),Empedocles(500-430 BC), Hippocrates (460-375 BC) : Health = harmony ; disease = dysharmony. “Nature is the healer of disease”. • Epicarus (341-270 BC) : Coping with emotional events improves the quality of life : “ataraxia”, impermeability of mind. • Buddha (563-483 BC) : India, eastern Asia, Confucius (551-479 BC) : China, philosophers and teachers. • From the Romans to Renaissance :In line with Hippocrates : Vis Medicatrix Naturae.

3. Claude BERNARD (1813-1878) 1. “Constancy of the internal environment is the condition that life should be free and independent”. Leçons sur les phénomènes de la vie communs aux animaux et aux végétaux, 1878. J.B. Baillère et fils, Paris (p.564). “No more pregnant sentence was ever framed by a physiologist”. The Scottish physiologist Haldane (Respiration, Yale Univ. Press,1922, p.427). “The organism maintains with the environment a precise and informed relation… in such a way that an equilibrium results from delicate and sustained compensations as it is with a very sensitive balance”. 3. “Physiology and pathology correspond each other and directly in such a way that healing corresponds to the recovery of a normal physiological state”. 4. Internal environment = fluids ; stability

4. Walter CANNON (1871-1945) Homeostasis “homeoios “ : like, similar “stasis” : stagnation, immobile, fixed = steady state Fight or Flight 1. In line with Bernard’s concept. • Homeostasis : «the stable state of fluid matrix, protected from change» • «All our living parts, both the gross and the minute, are intimately in contact with fluids, as if immersed in it». 2. The sympatho-adrenal system assure a «homeostatic condition of internal environment» ; adrenaline in blood stream : to all the internal organs. 3. The CNS is concerned : through its receptors (external environment) and via the ANS, through the internal environment. 4. Maintenance of homeostasis involves servo-mechanisms and setpoints at local levels. • When homeostatic adjustments fail : pathology.

5. Homeostasis as a biological necessity “It is chiefly freedom for the activity of the higher levels of the nervous system and the muscles which they govern. The alternative will be submission to the disturbances of any constants of the fluid matrix would impose upon us”. Cannon, 1939

6. Walter CANNON (1871-1945) • Organization for physiological homeostasis. Physiol. Rev., 1929, 9, 399. • Stresses and strains of homeostasis. Amer. J. Med. Sci., 1935, 189, 1. • The wisdom of the body, 1932, Norton and Co, NY. During the same period :  Cushing (Harvard, 1932) and his syndrome.  Marshall (Cambridge, 1936) reviews in detail the way in which endocrine activity was affected by external factors.

7. Hans SELYE (1907-1982)The “General Adaptation Syndrome (GAS)… A syndrome produced by diverse noxious agents”. Nature, 1936, 138, 32. • “The defects observed in different organs are constant and unvariable signs of damage to a body facing a demand or meeting the attack of any disease”. • GAS or “biologic stress syndrome” • Alarm reaction • Then, if continues : adaptive stage of resistance • Increase of granules secretion in adrenal cortex • Hemodilution, hyperchloremia, anabolism • Then, if continues : stage of exhaustion • “The concept of non-specificity in bodily reactions contrasts with the concept of specificity in medicine introduced by Pasteur”. • “Even mere emotional stimuli produce a severe alarm reaction ; the anterior pituitary receiving virtually no significant neural input, appeared nonetheless to be influenced by the central nervous system”. • Cannon : “I do not think these glands could help resistance and adaptation in general”. • Not physiology but disease.

9. Hans SELYE (1907-1982)« The stress of life » 1956 McGraw-Hill, NY “I should have called my phenomenon the «strain reaction» and that which causes it “stress”, which would parallel the use of these terms in physics. Hence, I was forced to create a neologism and introduce the word “stressor” for the causative agent, retaining stress for the resulting condition. Stress and strain in physics correspond to stressor and stress in biology and medicine”. The stress of life, 1956, pp. 50-51. “Stress is the non-specific result of any demand upon the body, be the effect mental or somatic”. “The exact nature of the stressor becomes largely irrelevant”.

10. 1940-1970 : Profound changes in medicine. ———— The Concept : “… More should be learned about the influence a social system has on the health of its members”. ———— - Donnison : Civilisation and Disease, 1938. - Halliday : Psychosocial Medicine : a Study of the Sick Society, 1948. • Wolff : Stress and Disease, 1952 (cf Engel). • Dohrenwend : Stressful Life Events : their Nature and Effects, 1974 (cf Hinkle). • Insel and Moos : Health and the Social Environment, 1974. • Kurstin : Theoretical Principles of Psychosomatic medicine, 1976. • Weiner : Psychobiology of Human Disease, 1977. • Henry and Stephens : Stress, Health, and the Social Environment, 1977.

11. 1948 : Cortisone P.S. Hench (and E. Kendall) 1949 : First report for a medical role of “substance E” (cortisone) in rheumatoid arthritis 1950 : Nobel Prize 1954 : More than 200 diseases treated by the hormone

12. A. Angelucci, Europ. J. Pharmacol., 2000, 405, 139-147 A. Munck et al, Endoc. Rev., 1984, 5, 25-44

13. A move from hypophysis to cortexA cognitive – motivational – relational theoryLazarus R. : Psychological stress and the coping process, 1966, McGraw-Hill, NY. • Stressors are external events or conditions that affect the organism : they impinge on an organism that has specific characteristics . • Lazarus R. “Adaptational equation” : Two central elements • cognitive appraisal : Plays a major role in the transaction between the person and the potentially stressful environment. Individual differences, of most relevance in human research, have to do with the cognitive appraisal of stressors. • Coping : After appraising the stressor, the organism will use one or more coping strategies in an attempt to adjust to the situation. Individual differences and predispositions play a key role either for successful coping (stress management, strategies, skills) or for maladjustement. “The explosion of interest in the various emotions is a very important and desirable change of fashion in the social and biological sciences, from an emphasis on a valuable but limited concept, stress, to a broad, richer and clinically more useful concept, emotion”.

18. John W. Mason A re-evaluation of the concept of “non specificity” in stress theory. J. Psychiat. Res., 1971, 8, 323-333 • Selye’s concept stands largely in the position of having been neither refuted nor confirmed experimentally. • There is an apparent incompatibility of the GAS with the concept of homeostasis ; the three phases have not been re-evaluated in terms of associated levels of pituitary-adrenal cortical activity. • A noteworthy aspect of Selye’s observation was that the anterior pituitary, while receiving virtually no significant neural input, appeared nonetheles to be influenced by the CNS. • The well established implication of psychoendocrine research for endocrine regulation seemed not to be appreciated.

19. Mason’s Principles - Psychological influences are among the most potent natural stimuli known to affect the pituitary-adrenal cortical activity, in particular novelty, uncertainty, unpredictability. - There are marked individual differences in the response to any particular situation. The response depends on how that individual interprets this particular situation, what are his goals, and what are his expectancies and defence mechanisms. • The measurement of pituitary-adrenal activity offers a particularly interesting, sensitive, and objective index of the psychological or emotional state of the individual.  “To all of us that have been involved in this type of research the Mason’s principles are amazingly representative of what we believe to be consensus”. A. Ursin, 1998.

20. Weiss J.M., 1972

21. J.W. HENNESY and S. LEVINE (1979)Stress, Arousal and the Pituitary System : a Psychoendocrine Hypothesis. Prog. Psychobiol. Physiol. Psychol., 1979, 8, 133-178. • Both stress and arousal are abstractions or hypothetical constructs that clarify independent/dependent variable relationships ; they are analogous concepts. • The pituitary-adrenal system is a part of the arousal system and is an extremely reliable and sensitive measure of arousal as well as stress. • The construction of a psychoendocrine model should begin with an identification and description of the cognitive mechanisms involved. • The major stimulations of arousal are novelty, uncertainty, and conflict. The cognitive operation common to all these independent variables is one of comparison and appraisal.

22. Adapted from A.R. Kagan and L. Levi, 1974

24. Corticosteroid receptors in the brain • 2 types : • Mineralocorticoid (MRs) Bind corticosterone-cortisol with high affinity • Glucocorticoid (GRs) : 1/10 the affinity of MRS • Hippocampus : both ; most other regions : GRs. • At rest : MRs already occupied when corticosteroid levels are low (GRs partially occupied). • Stress : GRs fully activated. • Activation of MRs : guarantee a stable background of neuronal firing, contributes to its « proactive » role in maintaining homeostasis. • Activation of GRs (+MRs) : enhanced calcium influx, stronger spike-frequency accomodation and marked responses to biogenic amines (in final, a reactive mode of recovery). • Reul JMHM, de Kloet ER. Endocrinology, 1985, 117, 2505-25011. • Joels M, de Kloet ER. Science, 1989, 245, 1502-1565. • De Kloet ER. Front. Neuroendocrinol., 1991, 12, 95-164.

29. From homeostasis to pathology

30. 1990-2000PROFOUND CHANGES IN AMERICAN MEDICINE : DELETERIOUS SOCIETIES AND HEALTH———— • A. Sen : Inequality reexamined, 1992. • S. Wolf, J.G. Bruhn : The Power of Clan, 1998. • N. Adler, M. Marmot, B.S. Mc Ewen, J. Stewart : Socio-economic Status and Health in Industrial Nations. Social, Psychological and Biological Pathways, 1999. • M. D. Glantz, J. L. Johnson : Resilience and Development : Positive Life Adaptations, 1999. • M. Marmot, R.G. Wilkinson : Social determinants of Health, 1999. • R. Wilkinson : Unhealthy Societies, The afflictions of inequalities, 1999. • D.G. Myers : The American Paradox, 2000. • R.D. Putman : Bowling alone, 2000. • Institute of Medecine : Health and Behavior. The Interplay of Biological, Behavioral, and Societal Influences, 2001. • I. Kawachi, B.P. Kennedy : The Health of Nations : Why inequality is Harmful to your Health, 2002. • I. Kawachi, L.F. Berkman : Neighborhoods and health, 2003. • M. Marmot, R.G. Wilkinson : Social determinants of Health: The solid facts, 2003. • M. Marmot : Status syndrome : How your social standing directly affects your health and life expectancy, 2004.

31. Social capital Social capital refers to aspects of social relationships, levels of trust among citizens norms of reciprocity and mutual aids, which act as moral resources for individuals and facilitate collective action for mutual benefit. It represents the resources available to individuals through their social affiliations and membership in community organizations. It inheres in the structure and quality of social relationships among individuals, norms and sanctions concerning the way that people behave toward one another. From : M. Marmot, 2004

32. Social rejection and social exclusion “Social exclusion and social rejection decreases pro-social behavior, interfere with emotional responses, impairs the capacity for empathic understanding of others”. “The social and physical pains share common physiological mechanisms. Moreover rejected people have impaired self-regulation abilities”. J.M. Twenge et al, J. Person. Social Psychol., 2007, 92, 56-66 G. Mac Donald, M.R. Leary, Psychol. Bull., 2005, 131, 202-223 R.F. Beaumeister et al, J. Person. Social Psychol., 2005, 88, 589-604

33. Social pathologies Low socio-economic environments, poor subjective social status and position on the social ladder, social inequalities, are associated with increased stress processes which, in turn, predict an increased frequency of diseases, behavioral pathologies and psychopathological conditions. Earlier the deleterious environments appear during infancy, more profound are the development of personality traits such as hostility and hopelessness. Epigenetic alterations of gene expression in selected brain regions are produced (prefrontal cortex, amygdala, hippocampus) that regulate cognitive-emotional responses to stress. These effects define an increased vulnerability for poor health, and psychopathology over the life span. Adapted from N.M. Cameron et al, “The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care ”, Neurosci. Biobehav. Rev., 2005, 29, 843-865

34. BIOBEHAVIORAL DISORDERS ... drug use and various addiction … impulse control disorders ... eating disorders ... violence and personality disorders ... disordered affective states and chronic anxiety … suicide … child psychopathology and behavioral disturbances ... hyperactivity and attentional deficits ... obsessive-compulsive states … chronic fatigue … sleep problems … muscular-skeletal pains etc... etc...

35. Deleterious (or protective) Perinatal Environments Genetic Background Development Epigenetic Mechanisms Life events Trauma Unhealthy society Coping Social support Resilience Vulnerable Phenotype Allostatic state Biobehavioral Disorders Drug abuse Psychopathology Systemic Diseases State / Trait Long-term Maladaptation

36. After the completion of my last effort to define stress (Levine and Ursin, 1991), I made myself the promise that I would never again engage in what I consider a futile exercise. S. Levine 2005, p. 3 (Handbook of stress and the brain, T. Steckler et al, ed.)

38. Robin Hood Index : the proportion of aggregate income that must be redistributed from rich to poor households in order to attain perfect equality of incomes across households From Kawachi and Kennedy The Health of Nations. 2002

39. From Kawachi and Kennedy The Health of Nations. 2002

40. From Kawachi and Kennedy The Health of Nations. 2002

41. From Kaplan et al, Brit. Med. Jl. 1996

43. “We define stress as state of disharmony, or threatened homeostasis. The adaptive response can be specific or can be generalized and more specific”. Chrousos G.P. and Gold P.W., JAMA, 1992, 267, 1244-1252

44. “Stress may be defined as a real or interpreted threat to the physiological or psychological integrity of an individual that results in physiological and/or behavioral responses. In biomedicine, stress often refers to situations in which adrenal glucocorticoids and catecholamines are elevated because of an experience”. in disturbance of homeostasis and reinstatement of the balance B. Mc Ewen, 2000, pp. 588-649, (Encyclopedia of stress, Fink G. ed.)

45. “The major problem with the concept of stress is that we are confronted with a composite, multidimensional concept. All existing definitions include some components. We can identify three main subclasses. These subclasses can be identify as the input (stress stimuli), the processing systems, including the subjective experience of stress and the output (stress responses). One basic difficulty is that these subclasses interact, as a complex system with feedback and control loops, no less but no more complicated than any other of the body’s self-regulated systems. This system affects many other biological processes and may function as a common alarm and drive system, whenever there is a real or apparent challenge to the self-regulating systems of the organism”. S. Levine and H. Ursin, 1991, p. 3-21, (Stress Neurobiology and Neuroendocrine M.R. Brown and G.F. Koob eds.)