Mind And Body: What's The Connection?

IT ALL CONNECTS: Ohio State's Janice Kiekolt-Glaser believes that the more mind-body medicine is used in general medicine, the better. Research into the effects of molecular pathways on brain and body functions is reviving old questions Backed by solid research in molecular biology and fueled by consumer interest, the role of the mind in bodily health is entering the arena of serious scientific consideration. Evidence of communication between the central nervous system (CNS) and the immune sy

By | March 2, 1998

Janice Kiekolt-Glaser

Backed by solid research in molecular biology and fueled by consumer interest, the role of the mind in bodily health is entering the arena of serious scientific consideration. Evidence of communication between the central nervous system (CNS) and the immune system at the molecular level is gaining acceptance in the research community, as work with animal models continues to explore how these pathways function. A next step is to determine if an individual's state of mind or emotions alter this network to affect human health. Meanwhile, managed-care organizations and hospitals across the United States already are responding to patient demand by offering many types of "mind-body" medical treatment.

This field focuses on "the interactions between mind and body and the powerful ways in which emotional, mental, social, and spiritual factors can directly affect health," according to the Web site literature of one of its most high-profile proponents, the nonprofit, educational Center for Mind-Body Medicine in Washington, D.C. The center lists self-awareness, relaxation, meditation, exercise, diet, biofeedback, visual imagery, acupuncture, herbalism, massage, musculoskeletal manipulation, self-hypnosis, group support, and prayer among its techniques.

Despite its funding of studies into the molecular bases of mind-body connections, the National Institute of Mental Health (NIMH) and its parent, the National Institutes of Health, have been criticized in Congress for bias against the emergent field (M. Wadman, Nature, 390:108, 1997).

"There's a very interesting history of not only ignoring but downright rejecting this field in terms of 'hard-core science,' which tends to focus inward, through the molecular level, rather than outward, toward psychological and social factors," notes Esther Sternberg, chief of the section on neuroendocrine immunology and behavior in the clinical neuroendocrinology branch at NIMH. "These disciplines have put on blinders against the other physiological, psychological, and social factors that could tend to modify those molecular effects.

KNOWLEDGE IS KEY: The traditional split between the art and the science of medicine should not prevent learning more about one or the other side, notes NIMH's Esther Sternberg.
"I think there's always been a split between clinical medicine or the art of medicine, which doesn't necessarily require knowing how a system works, and the science of medicine, which does require knowing how it works," adds Sternberg. "But understanding more about one or the other side shouldn't be mutually exclusive.

"Within the last few years, there's been a great deal more acceptance and coming together of both sides," she believes. "As more and more research shows the molecular and neuroanatomical connections that modify, exacerbate, or correct diseases, the field has become more and more credible, particularly among neurobiologists and immunologists."

She thinks endocrinologists have been relatively easy to convince, because hormonal factors have always been "real" to them. Noting an upsurge of recent research into cytokines-molecules secreted by the immune system that mediate communication with the CNS-she says, "If cytokines had been discovered by endocrinologists, they would have been called hormones."

Virtually all known cytokines or their receptors have been found in many CNS cells, including neurons. Moreover, an important difference between the roles of cytokines expressed within the brain and of cytokines that occur in peripheral parts of the immune system has been determined.

Neuronal cytokines play important roles in the death and survival of neurons, although the precise mechanisms of those roles are still being investigated. Overexpression of cytokines has been found in the brains of patients with AIDS, Alzheimer's disease, multiple sclerosis, vascular diseases, infectious illnesses, and nerve trauma. Despite the widely differing nature of these disorders, there is evidence that, in each case, neurodegeneration could be due to the toxic effects of cytokines released from inflammatory cells.

Peripheral cytokines act like hormones. Sparked by antigens or inflammatory stimuli, they can activate neuronal pathways that regulate the immune system. And they can stimulate such characteristic stress responses as anxiety or the lethargy of "sickness behavior" that is associated with illness.

Stress responses also can be activated by such external stimuli as a scare or a threat, triggering the "fight or flight" response through neuronal pathways, particularly the hypothalamic-pituitary-adrenal (HPA) axis. The resultant release of glucocorticoids, a group of steroids that prepare the body for action, also can downregulate the immune system to prevent it from overreacting and harming healthy cells. That can leave the body insufficiently protected against infections or malignancies. Conversely, some stimuli, such as inflammations, can blunt the HPA axis activity. This leaves the individual susceptible to excess immune activity and syndromes such as allergies, fatigue states, certain forms of depression, and inflammatory/autoimmune disease (E.M. Sternberg, Journal of Clinical Investigation, 100:2641-7, 1997; E.M. Sternberg, Nature Medicine, 3:264-7, 1997).

EMOTIONAL TRIGGER: Emotions are central to information exchange within an organism, Georgetown's Candace Pert believes.
According to the medical definition of "stress", when demands upon an organism exceed a critical level, an array of complex neuroendocrine responses is elicited that may have harmful effects on the body. Candace Pert, a research professor in the department of physiology and biophysics at Georgetown University Medical Center, suggests a new definition: "Stress is created when there are circumstances that place an individual in two competing, altered states of consciousness." She adds, "We all have many altered states, not just asleep or awake."

Her discover in 1972 of the receptor for opium (C.B, Pert, S.H.Synder, Science 179:1011-4, 1973) sparked a search for a naturally occuring or endogenous substance that would bind to the opiate receptor, affecting mood or temperament as the drug does. Such substances were soon identified as the enkephalin peptides and endorphin proteins. Nowadays, she's adamant that bridges must be built between the traditional, mechanistic view of biomedicine and a wider view that embraces the effect on health of emotions and spirituality, about which she says electical engineers and quantum physicists are starting to make formulations.

"Both perspectives must exist simultaneously," she declares. A good example of this necessary synergy, she says, is the relationship between stress and homeostasis, because without stress, the system wouldn't need information feedback. Homeostasis is about information flow and the challenge is to integrate that information. Molecules are obviously the vehicle of the information flow, but they are not the information itself.

"The thing about emotions that makes them facinating is that they're in the material and the immaterial realm. They're a transition element. In that way, ther're a key to information itself. Emotions are the trigger that moves an organism from one state of consciousness to another," she says. "I believe each of us creates health and disease on some level, by deciding which state of consciousness to pay attention to."

In recent years, Per's ideas have become increasingly solicited by the lay public. She lectures widely and recently published a book, Molecules of Emotion (New York, Simon & Schuster Inc., 1977).

Laying the groundwork for clinical trials, researchers have put much effort into animal models that demonstrate the role of chronic stress in affecting the immune system. Ohio State University microbiology professor Bruce Zwilling inoculates mice with a small dose of bovine tuberculosis (TB) mycobacterium, resulting in a latent infection. He then uses either of two types of chronic stress-restraint or social conflict-to activate the HPA axis in the mice, causing a recurrence of TB bacilli growth. Restraint typically involves placing the animals in conical centrifuge tubes for long periods, resting them, then returning them to the tubes. Social conflict pairs a sexually experienced male against an inexperienced male, resulting in aggressive behavior over an extended period. At specific times during the experiments, animals are killed and the growth of the microorganisms is isolated and plotted. The work of Zwilling and colleagues indicates that activation by stress of the HPA axis results in reactivation of the bacilli growth in mice (D.H. Brown et al., Infection and Immunity, 63:2243-7, 1995).

"People either have active or latent tuberculosis, and you can't measure any transition," Zwilling says in explaining the advantages of animal models. "I think the aggressive approach to treating TB is the right one, and that's using antibiotics. So, by controlling the HPA-mediated suppression of the immune system [in humans], you might get a decreased incidence of reactivation of the disease after latency."

At Ohio State University College of Medicine, a married couple have been collaborating since 1982 on clinical studies concerning the relevance of stress and immunity to human health. Janice Kiekolt-Glaser is a chools in the United States. He found approximately 50 that offered courses in alternative medicine. Of these, his personal determination was that only five taught a scientifically critical approach to the subject. Among the five was a course he started at Stanford in 1979. Other leading medical schools with such programs (none of which Sampson names as providing a "scientific approach") include those at Harvard University, Johns Hopkins University, Columbia University, and the University of California, San Francisco.

"Puffery" is how Sampson describes the surge of academic and consumer interest in mind-body medicine. "The finding of receptors and a few peculiarities in an in vitro system don't add up to a paradigm change or a breakthrough," he says. "If it weren't for the puffery going on, we would be teaching, as we are in some schools, that psychosomatic medicine is not as important as we once thought it was."

LEGAL WORRIES? A backlash against mind-body medicine could occur if patients begin to file malpractice lawsuits, suggests Penn's Paul Root Wolpe.
In the Center for Bioethics at the University of Pennsylvania, medical sociologist Paul Root Wolpe estimates that more than 35 U.S. medical schools now include courses in alternative or complementary medicine. "It's certainly true that interest in mind-body medicine has been exploding recently," he says, "and there are good reasons. It's low-tech, it's not expensive, it's a crowd-pleaser, and it's tied into a market that cares about the doctor-patient relationship.

"For a long time, medicine has been chastised for its hubris and for denying the validity of treatments that it now incorporates," he adds. "I think it's fascinating how quickly they've jumped onto this bandwagon."

Wolpe points out that many managed-care organizations across the U.S. also are rushing to offer mind-body medicine and other new modalities. He foresees a potential backlash if patients begin to file malpractice suits alleging they were directed into alternative therapies on the basis of lower costs than more traditional approaches, resulting in adverse effects on their health.

He traces the flurry of commercial interest in alternative medicine to a landmark 1990 survey of Americans using "unconventional" medical therapies. Extrapolating the survey's findings, the resultant academic paper estimated that Americans spent $13.7 billion in 1990 on such modalities (D.M. Eisenberg et al., New England Journal of Medicine, 328:246-52, 1993).

David M. Eisenberg, the Harvard internist who authored the paper with five other researchers, now directs the Center for Alternative Medicine Research, established in 1995 at Beth Israel Deaconess Medical Center, Harvard Medical School. The center's stated goal is to evaluate the safety, efficacy and cost-effectiveness of alternative medical therapies. Many of its projects receive funding from managed care organizations that offer their members alternative care modalities.

"That happens all the time in orthodox science," Wolpe notes. "As long as the science is good, it doesn't matter to me whether the people doing it are advocates or nonadvocates. It's not the managed-care people who are doing the research, it's the scientists."


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