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Psychoneuroimmunology (PNI)
(Mind-Body-Spirit Medicine)
Our internal chemicals, the neuropeptides and their receptors, are the actual biological underpinnings of our awareness, manifesting themselves as our emotions, beliefs and expectations, and profoundly influencing how we respond to and experience our world.
- Deepak Chopra, M.D.[1]
Around 200 AD, the Greek author Galen wrote that melancholic women are more susceptible to breast cancer than sanguine women. He was among the many physicians who have recognized through the years the importance of psychological factors in the prognosis of disease. [2] The fact that the mind can affect the course of illness has generally been accepted as fact by both physician and patient. Proving the mind-body connection scientifically took until the end of the 20th century before the knowledge and technology progressed far enough to conduct the research. Researchers in the fields of medicine, neuroscience, microbiology, psychology and social science are making great progress to prove that the connections between emotions and disease, the brain and the immune system, the mind and the body, are real.

The relatively young science of Psychoneuroimmunology, with slightly more than 20 years of study, is now scientifically establishing the interconnectedness of the mind, nervous, endocrine and immune systems. PNI views the body as a complex integrated circuit. When healthy, the brain, the blood, the glands and the nerves all work cooperatively to guard against disease. They work together through constant communication to mobilize and modulate each other’s power in combating disease and maintaining balance. [3,4] New molecular and pharmacological tools have made it possible for scientists and researchers to identify the components of this intricate network that exists between the various systems and the brain; this network allows the systems to signal each other continuously and rapidly. Chemical signals, Cytokines, produced by immune cells reach the brain, and the brain in turn sends its own chemical signals, neuropeptides to influence the immune system. The nervous, immune, and endocrine systems are in constant biochemical communication via this web of chemical signals. These same chemical signals can also affect behavior and the response to stress. Disruption of this communication network in any way, whether inherited or through drugs, toxic substances or surgery, exacerbates the diseases that these system guard against: infectious, inflammatory, autoimmune and associated mood disorders. [3,5]

The three traditionally separated fields of neuroscience, endocrinology and immunology, with their various organs—the brain, the glands, the spleen, bone morrow, and lymph nodes—are actually joined to each other in a multidirectional network of communication, linked by information carriers known as neuropeptides.
Candice Pert Ph.D. [6]

To understand the term Psychoneuroimmunology one can start by breaking it into and defining the component parts:
    Psyche - the mind component or study of psychology, the cognitive and emotional processes involving mood states.
    Neuro - the neurologic connections e.g. neurotransmitters and neuroendocrine secretions, or study of neurology
    Immunology how the immune system e.g. the cellular and humoral components is impacted, or the study of immunology.
Various Definitions of Psychoneuroimmunology:
The study of the interaction of behavioral, neural, and endocrine factors and the functioning of the immune system. [7]
The study of interactions, bidirectional communication occurring between behavior, brain, the immune and endocrine systems. [8]
The best working definition is the one below:
An interdisciplinary science that studies the interrelationships between psychological, behavioral, neuroendocrine processes and immunology.

Effect of Different Emotional States on the Mind-Body System
A considerable and growing body of evidence is demonstrating that life stress can alter immune function, thus impacting the body's ability to ward off disease and maintain health. Life stressors such as bereavement, marital separation, academic examinations, or caregiving of a spouse with Alzheimer have all been shown to impact the immune function. [9]

Stress, the Immune System and the Impact on Body
Chronic activation of cortisol, the body's response to stress, can produce unhealthy physiological outcomes. Some of these include: [10]

  • Increased blood pressure
  • Diabetes
  • Atherosclerosis
  • Immune Suppression
  • Bone Resorption (Osteoporosis)
  • Muscle Atrophy
Other effects of stress shown in various studies include: [11-13]
  • Chronic increased streptococcal infections.
  • Psychological stress can increase vulnerability to upper respiratory infections.
  • Increased incidence of mononucleosis in military cadets under increased academic pressure.
  • Medical students decline of natural killer cells reduction of lymphocyte proliferation and alterations in the regulation of Interleukin-2 and Interleukin-2 receptors around time of final exams.
  • Diminished antibody and immune cell response in medical students with more anxiety, higher stress and less social support.
  • Loss of few hours of sleep can temporarily depress the immune system.
  • Decreased Natural Killer activity with in those reporting increased loneliness.
Chronic stressors, lasting over periods of one or more years, not only increase the risk for depression but also are likely to alter the immune function. Compared to age-matched controls, family caregivers of Alzheimer patients are more likely to be psychologically distressed. Their bodies manifest this stress with significantly higher antibody titers to EBV and reduced percentages of total T lymphocytes and T helper cells, the body's main immune fighting components. [9]

In general, caregivers who report caregiving strain have higher levels of depression symptoms and have worse health practices than noncaregivers or caregivers who report no strain. Caretakers for spouse or parent with Alzheimer’s disease were more likely to have more severe colds than those without such responsibilities. In addition, following the death of their spouse, strained caregivers had improved health practices and no further increases in depression symptoms, antidepressant medication use or significant weight loss. This indicates that the the death of a spouse among strained caregivers represents a significant reduction in burden, reducing the stress load, rather than further tax the bereaved spouse's ability to cope. [14]

Bereavement, the Immune System and the Impact on the Body
Psychological response to bereavement, not merely the event, appears to contribute to the immune changes in this severe life stress. Individuals undergoing bereavement show alterations of cellular immunity including suppression of lymphocyte responses to mitogenic stimulation, reduction of NK cell activity, and alterations of T-cell subpopulations, generally indicators of reduced immune function. Women who's husbands had died showed increased plasma cortisol levels resulting in immunosuppression. Widowed noncaregivers had increased depression symptoms and antidepressant medication use, significant weight loss, but no change in overall health risk behaviors.[9,11,13]

Ability to Impact the Body with the Mind
Several recent investigations have suggested that psychiatric interventions that reduce psychological distress may have beneficial effects on cancer survival, indicators of the mind's ability to impact the body. Patients with advanced breast cancer who used self-hypnosis for pain control not only improved their quality of life but had a longer life expectancy. Other types of cancer patients demonstrated psychological and immunological by participating in psychosocial group therapy. [4,9]

Candice Pert Ph.D., one of the early researchers in the field of what is now known as psychoneuroimmunology, define "emotions" in scientific terminology to explain the science behind mind-body. She offers the following explanation of the molecules of emotions: [1]

Emotions—the neuropeptides and receptors, the biochemicals of emotion are the messengers that carry information to link the major systems of the body into one unit that we can call the body-mind. Emotions are cellular signals that are involved in the process of translating information into physical reality, literally transforming mind into matter. Emotions are at the nexus between mind and matter, going back and forth between the two and influencing both.
There is growing evidence that emotions of the mind influence the body. Substantial envidence now suggests that chronic hostility, depression and repression along with their acompanying negativity influence physical health and impeed recovery from illness. Sometimes the influence is positive e.g. when the immune system is enhanced to combat diseases, other times the influence is negative e.g. when heart disease (and the immune system) is negatively impacted by the effects of stress. Physiological disturbances such as high levels of cortisol, unhealth behaviors including substance abuse or increased risk-taking can also negatively impact health. Staying depressed, having a negative outlook may depress the immune system, whereas feeling up beat, maintaining a positive attitude may help to strengthen the immune system. These mind-body disturbances interact with environmental factors e.g. high fat diets, low exercise, smoking and hereditary predisposition to certain diseases e.g. cancer, heart, diabetes. Many believe it is not the stress per se, but rather chronic negative emotion combined with poor life-style choices that lead to a disruption of life's harmony which causes disease. [4,9,15,16]

The current research in the field of psychoneuroimmunology makes it difficult for the health care profession to continue ignoring the impact of the mind, the emotions or the spirit on the health or well-being of the body or on the disease and healing processes.

The Mind-Body-Spirit Interconnection
Since the times of the Greeks conventional medicine has traditionally utilized the biomedical model. This model focuses on dualism involving the mind and the body interactions. This model does not include the spirit. The biomedical model treats disease as a pathology that occurs within the person. The doctor's function is to control the pathology, repair the body and restore health. The limitation of this model is that it excludes any psychological, social or ecological factors. [17]

Body  Mind
Traditional Biomedical View

The traditional religious view also involves a dualism, but this one foccuses on the spirit-mind, ignoring the impact that either have on the body.

Spirit  Mind
Traditional Religious View

In contrast, the humanistic model utilizes a pleuralistic approach considering interactions and the interconnectedness between the mind, the body and the spirit when treating "dis-ease" within a person. The psychoneuroimmunology view is a pluralistic one that considers mind, body and spirit. [1,17]

Psychoneuroimmunology, Humanistic View

The current research in the field of psychoneuroimmunology is demonstrating the inter- connections of the mind, the body and the spirit. One is no longer able to focus on the mind as an abstract phenomenon that is separate from the processes of the body and the emotions. The health or well-being of the body can no longer ignore the impact of the mind, the emotions or the spirit on the process. [1,17]

The Impact of the Healer on the Patient

It is more important to know what sort of person has a disease
than to know what sort of disease a person has.


We are entering an era where it is becoming important to restore the "humanism" in medical care, where the focus is on a plurualistic view that includes the body, the mind and the spirit. One way of doing this would be by creating physician-healers, following the saged advice of Hippocrates where the physician gets to know (and has the time to get to know) the person that has the disease, not just concentrating on the disease process. [18]

The impact of the physician or other health care provider on their patients or clients is a central aspect of the therapeutic effectiveness. Simple, basis, humanistic techniques can have very powerful impacts. Some useful techniques include: [19-21]

  • Mere presence, listening to and being present for the patient.
  • Use of Touch.
  • Willingness to cry with the patient.
  • Maintaining continued trust in the physician.
  • Availability over time.
These techniques often rely upon the placebo response as their mechanism of action which relies heavily upon the relationship between the doctor and the patient. The placebo is believed to work because the subjectively pleasurable and meaningful stimuli associated with a healer is based on hope, trust and expectations objectively stimulates the patient's pleasure system, aiding in the healing process. Psychoneuroimmunology can also be used to explain the placebo effect, by understanding the interactions between the mind and the body; this very powerful biological effect can be used judiciously to help the healing process. Dr. Herbet Spiegel reminds us that "medical practice consists not only of diagnosis and treatment, but also of the careful tending of a patient's expectations and the unabashed willingness to comfort." [19-21]

Our biochemical messengers act with intelligence by communication information,
orchestrating a vast complex of conscious and unconscious activities at any one moment.
Deepak Chopra, M.D. [1]

In the last decade the technology in immunology and neuroscience has been developed to prove that the connections between emotions and disease, between the brain and the immune system, the mind and the body, are real, measurable and in some instances quantifiable. The current research in the field of psychoneuroimmunology is demonstrating the interconnections of the mind, the body and the spirit. Knowing how these interactions occur will help treat diseases and lead to development of new treatments for such illnesses based on stimulating various parts of the immune, neuro or endocrine systems to enhance healing. [19,20]

One is no longer able to focus on the mind as an abstract phenomenon that is separate from the processes of the body and the emotions. The health or well-being of the body can no longer ignore the impact of the mind, the emotions or the spirit on the processes of disease or maintaining health.  [1,17]

1.  Pert CB. Molecules of Emotion: The Science Behind Mind-Body Medicine. New York, N.Y.: Touchstone, 1997, p. 9.
2.  Dunn AJ. Interactions Between the Nervous System and the Immune System: Implications for Psychopharmacology. Part of The Fourth Generation of Progress  On-Line Edition. American College of Neuropsychopharmacology, 2000. Available at: .
3.  Weil A. Immunity, 2000. Previously available at:,1412,69,00.html when accessed in July 2001.
4.  Hammerschlag CA. Silverman HD. Healing Ceremonies: Creating Personal Rituals for Spiritual, Emotional, Physical and Mental Health. New York, N.Y.: A Perigee Book: 1997. p. 3. 
5.  Sternberg, EM. Gold, PW. The mind-body interaction in disease. Scientific American, 1997 Special Issue The Mind, Vol. 7 Issue 1, p8, 8p, 8c
6.  Pert CB. Molecules of Emotion: The Science Behind Mind-Body Medicine. New York, N.Y.: Touchstone, 1997, p. 184
7.  The American Heritage Dictionary of the English Language: Fourth Edition. Houghton Mifflin Company: 2000. Available at: .
8.  Maier SF, Watkins LR, Fleshner M. Psychoneuroimmunology: The Interface between behavior, Brain and Immunity. American Psychologist. 1994;49;1004-17.
9. Irwin M. Psychoneuroimmunology of Depression. Part of The Fourth Generation of Progress  On-Line Edition. American College of Neuropsychopharmacology, 2000. Available at: .
10. Sadek N, Nemeroff CB. Update on the Neurobiology of Depression. Medscape: Psychiatry and Mental Health Updates. August 2000.
11. McDaniel JS. Psychoimmunology: Implications for Future Research. Southern Medical Journal 1992;85:388-96.
12. Eichner ER. Calabrese LH. Immunology and Exercise: Physiology, Pathology, and Implications for HIV Infection. Med Clinics of N America 1994;76:377-87.
13. Ballieux RE. The Mind and the Immune System. Theoretical Medicine. 1994;15:387-95.
14. Schulz R, Beach SR, Lind B. Involvement in Caregiving and Adjustment to Death of a Spouse: Findings From the Caregiver Health Effects Study. JAMA. 2001;285:3123-3129. 
15. Friedman HS, VandenBos GR. Disease-Prone and Self-Healing Personalities. Hospital and Community Psychiatry. 1992;43:1177-79.
16. Achterberg J, Dossey B, Kolkmeier L. Rituals of Healing: Using Imagery for Health and Wellness. New York, N.Y.: Bantum Books, 1994, p. 21.
17. Tamm ME. Models of health and disease. British Journal of Medical Psychology. 1993;66:213-228.
18. Novack DM, Epstein RM, Paulsen RH. Toward creating physician-healers: fostering medical students' self-awareness, personal growth, and well-being. Academic Medicine 1999;74:516-520.
19. Lehrman NS. Pleasure Heals: The role of Social Pleasure-Love in its Broadest Sense-in Medical Practice  Arch Intern Med. 1993;153:929-34.
20. Levin JS. Religion and Health: Is there an association, is it valid, and is it causal? Soc Sci Med 1994;38:1475-82.
21. Sternberg, EM. Does Stress Make You Sick and Believing Make You Well? The Science Connecting Body and Mind. Opening Ceremony Talk, March 26, 2000 for Stress et Iimmunite.  Available at: .

This article is based on information originally prepared as part of the syllabus and lecture for the "Somatic Aspects of Loss & Grief," taught in August 2001 at the University of California Berkeley Extension as part of the Professional Program in the Study of Loss and Grief.

Patients carry their own doctor inside. They come to us not knowing that truth.
We are at our best when we give the physician who resides within each patient a chance to go to work.

Albert Schweitzer

This material is © 2002 by Kirsti A. Dyer, MD, MS, Journey of Hearts, All rights reserved.
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Contact Dr. Dyer at for permission to use materials from this website for other ventures.