Emotion and Immunology

NEARLY a century after some leading physicians first recognized the powerful role of the mind in health and healing, scientists have begun to decipher exactly how stress and other emotional states can influence the onset and course of disease.

Aided by new biochemical techniques and a vastly expanded understanding of immunology and neurochemistry, their studies show that emotions, acting through the brain, can affect nervous system function, hormone levels and immunological responses, thereby changing a person's susceptibility to a host of organic ills.

Depending on the circumstances, animal and human studies have revealed that emotional reactions can suppress or stimulate diseasefighting whiteblood cells and trigger the release of adrenal gland hormones and neurotransmitters, including endorphins, that in turn affect dozens of body processes.

The fast-growing field of research has even been given a new name - psychoneuroimmunology - and is finally beginning to win the respect of the modern medical establishment, which despite physicians like Dr. Osler had scorned or ignored previous suggestions of a strong mind-body link. Many of the studies are now being supported by various branches of the National Institutes of Health. More and more, as Dr. Osler recognized, the emotions are being considered necessary components of the cause as well as the treatment of most illness.

Although the influence of mind on body was well known to ancient healers and has dominated folklore to the present day, "scientific" medicine has until recently focused almost exclusively on physical causes for bodily illness. Only a few so-called psychosomatic diseases, such as asthma and ulcers, were said to have an emotional basis.

The new studies strongly indicate, however, that virtually every ill that can befall the body - from the common cold to cancer and heart disease - can be influenced, positively or negatively, by a person's mental state. By unveiling the mechanisms behind these effects, the studies point to new ways to prevent and treat some of the nation's leading killing and crippling diseases. They strongly suggest that psychotherapy and behavioral techniques should be an integral part of preventive and therapeutic medicine.

These are among the possibilities:

- Among people considered at a high risk for developing lung cancer or heart disease, behavioral therapy to diminish their response to stressful life events may be partly protective.

- Mental images might be used to help cancer patients wage a more effective immunological war against their disease. Dr. Carl Simonton of the Cancer Counseling and Research Center in Fort Worth has been using such a method, though his work is highly controversial and has been criticized for making cancer patients think they caused their disease.

- By "conditioning" someone to respond to an inert substance as if it were an active drug, it may be possible to treat an illness without experiencing the severe side effects associated with potent medication.

- Patients with autoimmune diseases, in which the body attacks itself as if it were a foreign tissue, might be trained to suppress their own destructive immune reactions. Similar techniques may be used in treating allergies, in which the immune system overreacts to an innocent substance.

- By testing people's reactions to stress, it may be possible to identify biochemical or immunological "markers" that can predict who is most likely to develop certain diseases. Physicians at the University of Nebraska, for example, are trying to identify people at high risk for heart attack or sudden death by examining the cardiovascular responses to stress triggered by catecholamines, a class of neurotransmitters.

According to Dr. George F. Solomon, a University of California psychiatrist who first suggested a link between immunity and emotions two decades ago, the new findings dispute the longstanding notion of classical immunology that the immune system functions independently of the brain. And, Dr. Solomon added, they finally put to rest the Cartesian dichotomy that has separated body and mind since the 17th century.

Brain's Physiological Role

"Mind and body are inseparable," he said. "The brain influences all sorts of physiological processes that were once thought not to be centrally regulated."

The studies also show that the traditional concept of "stress" as a demanding life event is too imprecise to use as a measurement of how stress affects health. What is distressing to one person may be stimulating to another. Rather, the researchers are finding, it is how a person responds to life events, not the events themselves, that influences susceptibility to disease. The studies indicate that failure to cope well with stress can impair a person's ability to fight off illness, whereas adequate coping with a high-stress life may reflect "psychological hardiness" that is actually protective.

For example, in preliminary results from a five-year study of heavy smokers, Dr. Margaret Linn and her colleagues at the Veterans Administration in Miami found that those who developed lung cancer experienced a similar number of emotional life events (such as marriage, divorce, family illness and job loss) as did smokers who thus far are free of cancer. But the cancer patients perceived these events to be more stressful and regarded themselves as more responsible for bad happenings.

Furthermore, Dr. Linn said, in the cancer patients with a high level of perceived stress, immunological reponses were significantly reduced even before the cancer developed. In another study at the Miami center, similar emotional factors were found among diabetics whose blood sugar frequently went out of control.

At Beth Israel Hospital in Boston, Dr. Steven Locke, director of the psychoimmunology research project there, has studied healthy undergraduate students. Like Dr. Linn, he found that those who reported high levels of psychological symptoms in response to stressful life events had only one-third the level of "natural killer cell activity" as did students with the same number of life events but little psychological reaction to them. Natural killer cells are a type of white blood cell that can instantly recognize foreign cells without having been previously exposed to them.

Dr. Steven Schliefer, working with Dr. Marvin Stein and Dr. Steven Keller at the Mount Sinai Medical Center in New York, has studied the effects of bereavement on immune functions. Among husbands whose wives ultimately died of breast cancer, the researchers showed a decided decline in white blood cell function within two months of the death.

The new studies, which examine people before they become ill, are scientifically far more impressive than previous research, in which patients with certain diseases were questioned about psychological symptoms and recent stressful happenings. In the old studies it was impossible to tell whether the emotions caused the disease or the disease caused the emotional reactions.

Even more impressive, however, are recent animal studies that have begun to clarify seemingly contradictory findings of previous research. The new findings show that immunological responses to stress are not simple and straightforward but rather vary according to laboratory conditions, time of day, species, duration and frequency of the stress, whether the animals are able to do something about the stress, and even which kind of stress is applied.

Rotation-induced stress (whirling an animal on a turntable), which researchers at the Pacific Northwest Research Foundation in Seattle report to be highly stressful to laboratory mice, is of little or no consequence to monkeys, who apparently enjoy being whirled about.

Furthermore, Dr. Vernon Riley, who until his death last year had headed the foundation's department of microbiology, showed that how the animals are housed can distort the experimental results. When he designed "low-stress" housing for his research animals, results were far more reliable. He and his colleagues showed that stressed mice experience a dramatic increase in the blood levels of an adrenal gland hormone, corticosterone, which can impair immune responses. The stressed animals suffered a decline in disease-fighting white blood cells and a loss of tissue from the thymus gland, an important immunological organ.

Cancers also grew faster and killed sooner in the stressed animals, as did an injected cancer-causing virus. By contrast, animals partly protected from environmental stress in the special housing units developed many fewer spontaneous breast tumors than did conventionally housed mice.

As for timing, when the animals were subjected to stress before the injection of tumor virus, tumor growth was inhibited, while stress applied after exposure to the virus speeded up the cancer. However, when stress was prolonged, the tumors remained smaller and the animals died no sooner than did mice not subjected to any stress. Dr. Riley said his studies indicate that if no underlying disease is present, stress will have no effect on infections or cancers.

Dr. Darrel Spackman, who took over Dr. Riley's studies, is now looking into the possibility of protecting animals against the harmful effects of stress. One prospect is a natural steroid hormone called DHEA (for dehydroepiandrosterone), secreted by the adrenal gland.

"If we can find protective, nontoxic compounds, perhaps we could give them to people at known stressful times, such as before surgery or during cancer treatment," Dr. Spackman said.

Another avenue of study has demonstrated the brain's involvement in the immune response and suggested a possible nontoxic route to controlling autoimmune diseases and administering "drug" therapy. Dr. Robert Ader, a University of Rochester psychologist, and Dr. Nicholas Cohen, an immunologist, succeeded in "conditioning" animals to suppress their immune systems when given an immunologically inert substance like saccharin.

Involvement in Conditioning

"It's hard to get conditioning without the involvement of the brain," remarked Dr. Ader, who edited the signature volume of the field, "Psychoneuroimmunology" (Academic Press, 1981).

In the experiment, sponsored by the National Institute of Neurological and Communicative Disorders and Stroke, mice with an autoimmune disease that mimics human systemic lupus erythematosus (SLE) were initially given saccharin along with an immunosuppressant drug; later, their immune systems became suppressed when they were given saccharin alone, and the saccharin-conditioned animals had less active diseases and lower death rates.

This approach may make it possible to manipulate the immune system using a minimum of toxic drugs, Dr. Ader suggested. Another possibility would be to use a conditioned response to alternate an innocuous placebo with a real drug, thereby minimizing hazardous side effects without sacrificing therapeutic potential.

Studies at Mount Sinai Medical Center in New York have also shown a a direct connection between the brain and immune responses. Dr. Marvin Stein and his colleagues were able to suppress immunological reactivity in guinea pigs by placing lesions on the hypothalamus, a master regulator in the brain. The animals with lesions were less likely to succumb to severe allergic attacks.