Biology 202
1999 Second Web Reports
On Serendip

As most of us have experienced in our lives, especially in college, when we are most stressed out we all of a sudden seem to get sick easier and react to pain in more extreme ways. In this case, our psychological state seems to have much control over the functioning of our bodies (and immune system). For another example, consider the case of Mr. Wright as reported by Dr. Bruno Klopfer:

Mr. Wright had a generalized far advanced malignancy involving the lymph nodes, lymphosarcoma. The patient had tried every available form of medicine and his condition had hopelessly deteriorated to the point where he was bedridden and gasping for air. [The doctors] agreed that he had only a few days to live. Then the man heard about an experimental drug called Krebiozen, which was in the process of being tested. He insisted on being included in the experimental trials. His doctors, feeling he had nothing to lose and would soon be dead anyway, out of compassion greed to give him the experimental drug. To their amazement, the man's tumors soon began to shrink dramatically and he was discharged from the hospital. Two months later, the man read news accounts of the research on Krebiozen that reported serious doubts with the drug. Within a matter of days, the man's tumors had returned and were again threatening his life. His doctor cleverly convinced him that a new and more potent shipment had been received and proceeded to give him injections of plain water. His tumors once again began to shrink dramatically. He remained healthy for seven more months until another news report declared 'Nationwide AMA Tests Show Krebiozen to Be Worthless as a Cancer Treatment.' The man died within two days (4).

One can see that the connection between the nervous system and the immune system is quite important, especially in the way that attitudes and emotions are processed by and can at the same time affect physiological or biochemical change. To what extent does our mind, for example, psychological state, control the processes of the body, for example, the immune system or pain processing? What, then, are the implications for natural healing and pain suppression in terms of the mind-body connection?

Psychology of Immunity

It has been documented in many cases that positive attitudes and emotions can affect the biochemistry of the body to enable personal healing. This is, in essence, the nature of the placebo affect, such that "The placebo is the doctor who resides within" (11). The placebo affect has been shown to be a healing factor in hypertension, cardiac pain, headaches (implicating the autonomic nervous system); diabetes, menstrual pain, adrenal gland secretion (implication the endocrine system); colds, fever, asthma, and cancer (implicating the immune system). This demonstrates a corollary interaction between the mind and the body in terms of health and healing.

The study of psychoneuroimmunology^{(Endnote 1)} has allowed us an insight into these interactions between the nervous system and immune and endocrine systems. It is important to note that there are several types of experimental data which have shown the nervous system's influences on the immune system:

1) There is anatomic and chemical evidence for innervation of lymphoid tissue by the CNS, indicating direct neural access to organs of immune system (1),(9),(10);

2) Immune responses change according to stimulation or inhibition of the hypothalamus (and changes in neurotransmitter levels) and vice versa, indicating high degree of intercommunication (1),(9);

3) Lymphocytes have receptors for neurotransmitters of the nervous system (1), (9), (10);

4) Psychological factors such as stress and depression influence the process of disease onset (1), (2), (3), (4), (9), (10).

Two pathways have been found that link the brain and the immune system- the autonomic nervous system and the neuroendocrine outflow through the pituitary (9). In both cases, molecules are released which are capable with interacting with cells of the immune system. Lymphocytes, macrophages, and granulocytes, which are key cells involved in immunity (i.e. white blood cells), all have receptors for neurotransmitters released from nerve fibers which synapse at lymphoid tissues. The hypothalamus seems to be the main transducer of information from the nervous system to the immune system. Not only are neuronal signals of the brain converted to "messenger molecules" to regulate the body, but also the immune system seems to be able to communicate directly with the hypothalamus via molecules called immunotransmitters (11). There are bi-directional circuits between the central nervous system and the immune system, as evidenced by the fact that activation of the immune system results in an increased rate of neuronal firing in the ventromedial nucleus of the hypothalamus at peak production of antibodies (9).

Thus, knowing the anatomical and chemical connection between the nervous system and the immune system, the fact that certain psychological states affect immunity is not a surprise. For example, psychosocial factors such as stress and depression are implicated in initiation and progression of various physiological processes that involve changes in the natural defense mechanism of our body. Of course, stress is not always considered to be harmful, especially for our ancestors who required this "fight-or-flight response" capability. Some physiological signs of the stress response are increased blood pressure, respiratory rate, heart rate, blood flow to muscles, and perspiration (1). In an emergency, these reactions are essential to survival. However, in cases where this response is regularly experienced, especially over long periods of time, these physiological changes can lower resistance to illness. For example, in a study of medical students during exam period as opposed to a control (non-exam) period, there was a measured drop in activity of NK cells^{(Endnote 2)} and a decrease in proportion of helper T cells^{(Endnote 3)}. In addition, students reported a higher incidence of symptoms of illness during the exam times (9).

Depression has also been shown to negatively affect the immune system. Clinical depression is associated with a decrease of NK cells, T and B lymphocytes, and helper T cells (9). Additionally, transient states of depression have also been shown to affect immunoglobulin^{(Endnote 4)} levels. A study on college students was performed to measure effects of emotions on IgA (one type ofimmunoglobulin) levels, where half watched a morbid film on World War II and the other half watched an inspirational film on Mother Theresa. The latter group showed increased IgA concentrations (1), indicating a change in immune responsiveness simply due to emotions evoked by a film.

The implications of these pathways of immune responsiveness and psychological state are very important. The arousal of lymphoid organs and capability of neurotransmitters to interact with cells of the immune system open up a new dimension of possibilities in terms of health and healing. If stressful situations can lead to changes, usually negative, in immune function, can we now consider the possibility that relaxing or pleasurable situations can cause opposite physiological changes? As we see in the case of Mr. Wright at the beginning of the paper, perhaps positive attitudes, relaxation techniques, and other methods of psychological control can lead to positive affects on our health.

Mind/Body Medicine- relaxation, hypnosis, and humor

Thus far we have seen that immune response can be affected by emotional or psychological state. Indeed, it may be a difficult and ridiculous jump to say now that keeping a positive outlook on life will keep you healthy. However, the next logical step, especially for health care professionals and us, as neurobiologists, is to look at the power of behavioral and psychological interventions in treating pain and disease, aiding recovery and rehabilitating disability.

A mirror image to the stress (fight-or-flight) response, a "relaxation response" has been identified which may enhance immunity. Physiological changes include reduced blood pressure, respiratory rate, heart rate, blood flow to muscles, and perspiration (1). There are many techniques that can be used to induce the relaxation response, and thus possibly increase the effectiveness of the body's defenses and self-repair mechanisms. These techniques include meditation, hypnosis, mental imagery, breath therapy, biofeedback, and others.

Hypnosis and meditation involve a state of conscious relaxation where sensory contact with the environmental is continually maintained (8). This focused attention can be either self-induced or aided by a therapist's calm, monotonous, rhythmic tone of voice; ideally, this results in a relaxation response. In medical settings, hypnosis and meditation have been used to control postoperative pain, lower patient anxiety, diminish blood flow to a surgical site and is useful in psychosomatic conditions^{(Endnote 5)} such as allergy, insomnia, and headaches (5). There have even been examples of people undergoing surgery without anesthesia and reporting no sense of pain. Focused concentration in this form is also used in rehabilitation and sports to enhance performance, confidence, and decrease pain and anxiety. The physiological changes associated with meditative techniques, in addition to the relaxation response, are increased brain-wave activity in the form of alpha and theta waves as seen in EEG studies (6).

In a study on subjects recruited from an orthopedic emergency department, the acceleration of tissue healing after bone fracture was examined in relation to hypnotic intervention. One group received hypnotic treatments in the forms of office visits with a psychologist certified in clinical hypnosis as well as take-home audiotapes, while the other group received no additional treatment except for routine examinations, pain assessment, etc... The results showed trends towards increased healing rates for the hypnosis group in addition to improved ankle mobility, functional ability to descend stairs, and lower use of pain medicines (5). Indeed, these results are persuasive examples of the power of the mind, whether they are attributed to a placebo response, a relaxation response, or a hypnotic/ meditative response. Whatever the choice of words, this study demonstrates the potent connection between the nervous system and immune system and the important implications for health and healing.

Another example of the connection between psychological state (i.e. nervous system) and the immune system is in the case of "laughter as the best medicine". This is slightly more confusing, however, because the actual physiological response to laughter is synonymous with a stress response: increased heart rate, chaotic respiratory patterns, increased blood flow to muscles (especially of the face), and even violent bodily reactions such as hiccups. However, studies show that "mirthful laughter increases the spontaneous lymphocycte blastogenesis and the natural killer cell activity" (7). In another study, the concentration of salivary immunoglobulins^{(Endnote 6)} increased after the subjects watched a humorous film (7). Indeed, positive emotions seem to enhance the immune response while negative emotions, such as depression and stress, suppress it.

In conclusion, natural healing responses of the body cannot be ignored, whether in the form of the placebo affect or psychoneuroimmunologic connections exemplified by hypnosis, meditation, and laughter. Knowledge of the actual mind-body communication and healing properties can be very helpful in dealing with any psychological or physiological illness, especially in stress-related conditions and chronic illnesses. Indeed, there is much research that needs to occur in order to gain full understanding as to the mechanism of mind-body connections and "alternative" methods of healing. However, it cannot be denied that the capacity for self-healing in conjunction with medical techniques is quite powerful. "Society has long supported research into chemical and physical agents and treatments; it should now be equally excited by the scientific challenge of harnessing the powerful influence psychological and social variables have on our health" (4).

WWW Sources

2)Mayo Clinic-- Stress

3)Psychosomatic Medicine

4) Center for the Advancement of Health

5) Alternative Therapies

6) Lexis-Nexis search: Kutz, Borysenko, and Benson. "Meditation and Psychotherapy: A Rationale for the Integration of Dynamic Psychotherapy, the Relaxation Response, and Mindfulness Meditation". American Journal of Psychiatry, Jan. 1985; 142:1-8.

7) Physiological Response to Humor

8) Hypnosis

9) Lexis-Nexis search: Ader, Cohen, and Felten. "Psychoneuroimmunology: interactions between the nervous system and the immune system". Lancet, Jan. 14, 1995; 345(8942): 99-103.

10) Lexis-Nexis search: Mahaney, Francis. "Psychoneuroimmunology: Can the Brain and Immune System Communicate?" Journal of the National Cancer Institute, May 2, 1990;82:738-739.

11)Rossi, E.L. "The Psychobiology of Mind-Body Healing". Norton & Co., Inc.: New York, 1986.

Endnotes

2-NK cells are natural killer cells which are important in fighting viruses

3- helper T cells invoke an immune system response to infection

4- secreted immunoglobulins are antibodies which are critical in defense against bacteria and viruses

5- psychosomatic conditions involve both psychological and physiological problems

6- salivary IgA is a first line of defense mechanism against the entry of infectious organisms


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