Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

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Protective and Damaging Effects of Stress Mediators

Over the last several decades, epidemiological studies have been enormously
successful in identifying risk factors for major diseases However, most of this
research has focused attention on risk factors that are relatively proximal causes of
disease such as diet, cholesterol level, exercise and the like We question the
emphasis on such individually-based risk factors and argue that greater attention
must be paid to basic social conditions if health reform is to have its maximum
effect in the time ahead There are two reasons for this claim First we argue that
individually-based risk factors must be contextualized, by examining what puts
people at risk of risks, if we are to craft effective interventions and improve the
nation's health Second, we argue that social factors such as socioeconomic status
and social support are likely 'fundamental causes" of disease that, because they
embody access to important resources, affect multiple disease outcomes throughmultiple mechanisms, and consequently maintain an association with disease even when intervening mechanisms change Without careful attention to these
possibilities, we run the risk of imposing individually-based intervention strategies
that are ineffective and of missing opportunities to adopt broad-based societal
interventions that could produce substantial health benefits for our citizens

Social Conditions as Fundamental Causes of Disease

Objective: This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses. Data Sources: Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE. Data Extraction: Independent extraction and cross-referencing by us. Data Synthesis: Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis . In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. Conclusions: This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed. (Arch Intern Med. 1993;153:2093-2101)

https://jamanetwork.com/journals/INTEMED/articlepdf/617820/archinte_153_18_004.pdf

Stress and the Individual: Mechanisms Leading to Disease

Socioeconomic status (SES) is consistently associated with health outcomes, yet little is known about the psychosocial and behavioral mechanisms that might explain this association. Researchers usually control for SES rather than examine it. When it is studied, only effects of lower, poverty-level SES are generally examined. However, there is evidence of a graded association with health at all levels of SES, an observation that requires new thought about domains through which SES may exert its health effects. Variables are highlighted that show a graded relationship with both SES and health to provide examples of possible pathways between SES and health end points. Examples are also given of new analytic approaches that can better illuminate the complexities of the SES-health gradient.

Socioeconomic status and health: The challenge of the gradient.

Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses

Background. It is not known whether psychological stress suppresses host resistance to infection. To investigate this issue, we prospectively studied the relation between psychological stress and the frequency of documented clinical colds among subjects intentionally exposed to respiratory viruses. Methods. After completing questionnaires assessing degrees of psychological stress, 394 healthy subjects were given nasal drops containing one of five respiratory viruses (rhinovirus type 2, 9, or 14, respiratory syncytial virus, or coronavirus type 229E), and an additional 26 were given saline nasal drops. The subjects were then quarantined and monitored for the development of evidence of infection and symptoms. Clinical colds were defined as clinical symptoms in the presence of an infection verified by the isolation of virus or by an increase in the virus-specific antibody titer. Results. The rates of both respiratory infection (P<0.005) and clinical colds (P<0.02) increased in a dose-response manner...

https://www.nejm.org/doi/pdf/10.1056/NEJM199108293250903

Psychological Stress and Susceptibility to the Common Cold

After completing questionnaires assessing stressful life events, perceived stress, and negative affect, 394 healthy Ss were intentionally exposed to a common cold virus, quarantined, and monitored for the development of biologically verified++ clinical illness. Consistent with the hypothesis that psychological stress increases susceptibility to infectious agents, higher scores on each of the 3 stress scales were associated with greater risk of developing a cold. However, the relation between stressful life events and illness was mediated by a different biologic process than were relations between perceived stress and illness and negative affect and illness. That these scales have independently relations with illness and that these relations are mediated by different processes challenges the assumption that perceptions of stress and negative affect are necessary for stressful life events to influence disease risk.

Negative life events, perceived stress, negative affect, and susceptibility to the common cold

OBJECTIVES. This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS. The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS. Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness follo...

Smoking, alcohol consumption, and susceptibility to the common cold.

The patterns of disease caused by five common viruses which infect the respiratory tract are described. The viruses were strains of rhinovirus types 2, 9, and 14, a strain of coronavirus type 229E and of respiratory syncytial virus. Volunteers were given nasal drops containing a low infectious dose of one of the viruses, quarantined from 2 days before to 5 days after inoculation, and examined daily by a clinician using a standard checklist of respiratory signs and symptoms. Only subjects who developed clinical illness accompanied by viral shedding and/or specific antibody production were analysed [n = 116]. The results confirm indication from earlier studies that the main difference between colds induced by different viruses is in duration of the incubation period. Patterns of symptom development were not substantially different with different viruses. Analyses of signs and symptoms in different categories, e.g. nasal symptoms v. coughing, justify treatment with different drugs either successively or simultaneously.

Signs and symptoms in common colds.

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50). At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months). In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275). Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue.

D. A. J. Tyrrell

Papers

Psychological Stress and Susceptibility to the Common Cold

Negative life events, perceived stress, negative affect, and susceptibility to the common cold

Smoking, alcohol consumption, and susceptibility to the common cold.

Signs and symptoms in common colds.

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue.