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Science / Medicine : SENSITIVE ARMOR : Multidisciplinary Effort Persues Link Between Mental State and The Body’s Succeptibility to Disease

<i> Harry Nelson is a former Times Medical Writer, now retired and freelancing in Woodland Hills</i>

More than 2,000 years ago, the Greek physician Galen noted that mentally depressed women seemed unusually prone to developing cancer. Since then, countless clinicians have made similar observations linking stress, emotions and attitude with susceptibility to disease and with the ability to recover from illness.

While anecdotal evidence for the link is abundant, those who are convinced that a link exists have lacked the kind of scientific evidence needed to explain how psychological states are translated into physical effects.

By what mechanism might a depressed feeling trigger illness or, contrarily, a happy disposition help to ward it off?

Answers to those questions are beginning to emerge from a new area of scientific investigation that is barely a decade old. Called psychoneuroimmunology (PNI), this multidisciplinary effort concentrates on the interaction between the central nervous system--the brain or “mind"--and the immune system, which is the body’s principal defense against cancer, infectious diseases and invasion by foreign substances.

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The aim of the neuroscientists, immunologists, psychologists, psychiatrists and others engaged in this investigation is to understand the nature of the “mind-body” link so that perhaps methods can be developed to use it in beneficial ways. Laboratory scientists at major centers around the country are exploring on a microscopic level the physical pathways by which this communication may take place.

The immune system consists of a vast array of cells that include lymphocytes, T-cells, B-cells, macrophages and plasma cells, as well as a number of chemicals which are toxic to foreign invaders.

A number of findings within the last few years point to the possibility that a surprising amount of communication takes place between the nervous system and the immune system. A basic finding was the discovery of a mesh of nerve fibers that infiltrate the spleen and other places in the body that are rich in a variety of immune cells.

At first it was believed that these nerve fibers were there to control blood vessels. But now it seems clear that part of their function is to become involved with T-cells and macrophages.

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David L. Felten of the University of Rochester School of Medicine and others have reported that the tips of the nerves are in direct contact with T-cells. The nerve fibers release a chemical neurotransmitter, norepinephrine, which Felten proposes may transmit messages from the nerve to the T-cell.

It has also been established that the surface of T-cells bears the proper kind of receptors needed to make contact with norepinephrine. Furthermore, there is reason to believe that cells in the immune system have other receptors that allow them to react to other brain chemicals, including a class called peptides. Experiments indicate that some peptides cause the immune cells to proliferate; others inhibit those cells.

Still more supportive of the belief in the mind-body link have been studies showing that the communication between brain and immune system is in both directions.

For example, experiments have shown that the electrical activity of neurons in the hypothalamus, a brain region involved in a range of activities including sleep, appetite regulation and sex hormone production, is altered by the immune system chemicals.

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According to Dr. Lewis J. Judd, director of the National Institute of Mental Health, these findings have gained new importance because of the AIDS epidemic and the possibility of finding ways to ease the illness through use of the mind-body connection.

One possible application of any knowledge gained could be in the treatment or prevention of depression, which affects not only AIDS patients but many others as well.

The researchers suspect that depression may have a negative effect on the immune system’s ability to function normally. For example, Judd said, it is not clear why some AIDS patients move from infection by the AIDS virus quickly into full-blown disease, while others take years to develop symptoms.

Although no proof yet exists that psychosocial factors influence disease susceptibility, studies aimed at exploring the issue are under way. With Institute of Mental Health funding, Dr. Jack Gorman of the New York State Psychiatric Institute and Columbia University heads a study aimed at learning the role of depression in hastening the progression of AIDS. The study, which began in March, will follow 500 antibody-positive patients and an antibody-negative control group for five years by giving them extensive psychological, medical and neurological workups every six months.

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Gorman’s hypothesis is that depression and stress will be predictors of rapid decline. If the hypothesis is confirmed, he and others believe that it may be possible to work out therapy programs to reduce the destructive effects of depression on the immune system.

At the University of Pittsburgh and Yale University, researchers are winding up another study aimed at testing whether counseling depressed patients with colon cancer or melanoma improves their survival rate.

Sandra M. Levy, a University of Pittsburgh psychologist, said counseling “clearly” reduced the depression and pessimism. Those patients whose depression had been reduced, she said, had normal levels of the immune cells that attack cancer. But because the final analysis has not yet been completed, she was unable to give details on survival.

Other studies are looking into various aspects of the brain-immunity relationship. At UCLA, Dr. John Fahey, an immunologist, and psychologist Margaret Kemeny are checking the rate of decrease in the number of “helper” cells in AIDS patients and are attempting to correlate the steepness of the decline with various psychosocial factors in their lives.

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At the Sepulveda Veterans Administration Hospital in Los Angeles, Dr. George Solomon, a pioneer psychoneuroimmunology researcher, is looking for psychological traits that appear to be associated with survival. He has reported that AIDS patients who are long survivors tend to be able to say no when asked to do a favor. Solomon says this indicates that assertiveness, ability to say no and the ability not to become over-burdened or self-sacrificing are beneficial traits.

The interaction between the nervous and immune systems may have significance for diseases other than AIDS and cancer. Among them are multiple sclerosis and myasthenia gravis--both crippling neurological diseases--and asthma and arthritis. In each of these afflictions there is a breakdown in the normal functioning of the immune system.

Some studies suggest that peptides released by the nervous system into the respiratory tract in the case of asthma, and into joints for arthritis, worsened the symptoms caused by the abnormally functioning immune system. Certain intestinal ailments such as inflammatory bowel disease may also be worsened by brain chemicals released under emotional stress.

What all of this seems to mean is that a kind of “hard wiring” system exists which appears capable of passing messages between the nervous system and the immune system that can be either beneficial or destructive to the patient’s welfare, and that mental processes may influence to some degree which effect occurs.

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“People have assumed that communication between the brain and the immune system doesn’t occur, but communications are taking place,” says Robert Ader of the University of Rochester, a psychologist whose work in the 1970s helped stimulate interest in psychoneuroimmunology.

In his study, Ronald Glazer of Ohio State University showed that the stress of taking a medical school exam can activate a latent herpes virus infection.

As a further indication that mood can make a difference, Glazer reported that the immune system suppression was even greater in students who were lonely. Similar indications of immune suppression have been reported in family members who care for victims of Alzheimer’s disease.

Like many of his colleagues, Carmine Clemente, professor of anatomy at UCLA and former director of its Brain Research Institute, is guardedly hopeful that better understanding of the brain-immune system connection will prove useful to medicine.

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“In the early days (of brain research), many challenged the belief that the brain secretes chemicals. Now we know the brain secretes at least 30 or 40 different ones,” Clemente said. “Today we are in the earliest stages of trying to identify substances that relate the brain to the immune system.”

THE IMMUNE SYSTEM

When bacteria, viruses or other foreign particles enter the body, a complex of cells rush to fight off the invaders. The body’s artillery consists of lymphocytes, T-cells, B-cells, macrophages and plasma cells that produce antibodies and chemicals that destroy foreign substances.

THE LYMPHATIC SYSTEM

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The lymphatic system is a network of small vessels that carries excess fruid from the body tissues back into the blood circulation. During an infection, lymph nodes drain the infected tissue, filtering out harmfull particles.

THE SPLEEN

The spleen is a mass of two kinds of lymphoid tissue; white pulp produces lymphocytes; microphages in red pulp filter out old or damaged cells, debris and bacteria. The spleen is also a store of iron and an aid in the development of immunity.

THE HYPOTHALAMUS

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The brain region involved in a range of activites and proven sensitive to immune system chemicals.


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