Does Stress Cause Disease? It Doesn't Help, Reviewers Say

PITTSBURGH, Oct. 10 -- There is strong evidence suggesting -- but not proving -- the existence of a causal link between psychological stress and chronic conditions such as depression, cardiovascular disease, and HIV/AIDS, asserted researchers here.

"Other areas in which evidence for the role of stress is beginning to emerge include upper respiratory tract infections, asthma, herpes viral infections, autoimmune diseases, and wound healing," wrote Sheldon Cohen, Ph.D., of Carnegie-Mellon University, in today's issue of the Journal of the American Medical Association.

In their review article, based on a paper commissioned by the Institute of Medicine, the authors examined evidence linking stress to chronic diseases by two essential pathways: the hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic-adrenal-medullary system.

"Cortisol, the primary effector of HPA activation in humans, regulates a broad range of physiological processes, including anti-inflammatory responses; metabolism of carbohydrates, fats, and proteins; and gluconeogenesis," they wrote.

"Similarly," they said, "catecholamines, which are released in response to sympathetic-adrenal-medullary activation, work in concert with the autonomic nervous system to exert regulatory effects on the cardiovascular, pulmonary, hepatic, skeletal muscle, and immune systems."

Chronic or repeated activation of these systems through stress could lead to increased risk for both mental and physical disorders by interfering with the ability of those systems to control other physiological processes, the authors wrote.

They noted that stress can increase the risk for cardiovascular disease by impairing vagal tone, and that it can effect the regulation of immune and inflammatory processes, with a potential for contributing to depression, infectious diseases, autoimmune conditions, coronary artery disease, and some cancers, such as those that are virally mediated (cervical cancer, for example).

"Psychological stress might alter immune function through direct innervation of lymphatic tissue, through release of HPA and sympathetic-adrenal-medullary hormones that bind to and alter the functions of immunologically active cells, or through stress-induced behavioral changes such as increased smoking," they suggested.

But the question of whether stress actually causes diseases is a trickier one to answer, they suggest, noting that it would be unethical to subject human volunteers to stress to see whether it could cause serious disease.

Yet real-life evidence from studies looking at associations between stressful life events and disease reveal intriguing clues, the authors wrote.

For example, in some studies of major depressive disorder, 50% to 80% of patients reported a stressful event such as the death of a spouse in the months prior to the diagnosis.

"Although most investigations have focused on life events as triggers of depression onset, increased stress also predicts the clinical course of major depression, including features such as longer duration, symptom exacerbation, and relapse," they wrote. "Evidence also suggests that events that occur concurrently with treatment reduce positive response."

Similarly, work with animal models and observation of healthy adults and cardiac disease patients point to an association between stress and myocardial ischemia, and activation of both inflammatory and coagulatory mechanisms, they wrote.

In addition, prospective studies have found strong associations between psychological stress and cardiovascular disease morbidity and mortality.

The evidence for a link between stress and HIV/AIDs comes from studies detecting a link between stress from cumulative negative life events and HIV progression, they noted.

"For example, among HIV-positive men, each additional moderately severe event increased the risk of progressing to AIDS by 50% and of developing an AIDS-related clinical condition by 2.5-fold," the authors wrote. "Moreover, stress has been found to influence the course of virally initiated illnesses to which persons with HIV are especially susceptible. These studies are supported by experimental research with animals wherein exposure to social stressors results in decreased survival."

The evidence for the effect of stress on cancer in its earlier stages is shakier however, although tumors with a viral influence, such as cervical adenocarcinomas or hepatocarcinomas, may be exacerbated by the immune-dampening effects of stress, the authors suggested.

"Evidence derived from prospective observational studies provides support for stress as an important factor in certain diseases but cannot establish a causal relationship," the authors wrote.

"However," they noted, "the results of these studies are consistent with those of natural experiments regarding the effects of real-life stressor exposure on disease risk; with those of laboratory experiments showing that stress modifies disease-relevant biological processes in humans; and with those of animal studies investigating stress as a causative factor in disease onset and progression. This consistency of research findings strongly supports the hypothesis of a causal link."

The Institute of Medicine Committee on Psychosocial Services to Cancer Patients and Families in Community Settings commissioned the paper on which the article is based.