• Definition:

    • Environmental conditions that require behavioral adjustment.

    • Defined by Hans Selye in 1936 as “the nonspecific response of the body to any demand.”

  • Stress is not new in terms of human evolution, but we have many "psychological stressors" now that primitive men and women did not have, such as stock market crashes, unemployment, terrorism, urbanization, and the changing roles of men and women in society.

  • The American Institute of Stress in Yonkers, New York estimates that stress-related complaints may be responsible for up to 75% of symptom-prompted visits to primary care physicians.

  • It has been estimated that 85% of all illnesses are caused or aggravated by stress (Lewis HR, Martha E. Psychosomatics. 1972).

  • Many best sellers have been written about stress, especially the psychology of stress.

  • Physiologically, stress triggers an involuntary response labeled the fight-or-flight response, characterized by increased respiratory rate, blood pressure, pulse, and increased blood flow to the muscles.

  • The same response is triggered whether the stress is real and physical (an animal attack) or imagined and psychological (dread or fear about the future).

  • From an evolutionary perspective, the fight-or-flight response was adaptive, but we are now victims of our past, in that chronic stress which is so common in this era leads to chronic increases in epinephrine and cortisol levels in the bloodstream, with resultant chronic hypertension and adrenal and immune system suppression as well as loss of muscle mass and deposition of visceral fat, which produces even more cortisol (Selye H. A Syndrome Produced by Diverse Nocuous Agents. Nature. 1936).

  • History

    • The word ‘stress’ was first used in 1926 by Walter Cannon, a Harvard professor – he used this word to describe adverse events that reduced homeostasis. Cannon published The Wisdom of the Body in 1932.

    • Hans Selye – identified the HPA axis as the mediating stress, and formulated General Adaptation Syndrome – the 3 stages of stress

      • Arousal – rapid increase in catecholamines, slower increases in cortisol levels.

      • Adaptation – sustained increase in catecholamines and cortisol levels, which is associated with insulin resistance, hypertension, and alterations of thyroid hormone and sex hormone metabolism.

      • Exhaustion – low levels of catecholamines and cortisol, associated with degenerative diseases of aging.

    • Research (Hess, 1940's) using electrical stimulation studies in cats, has shown that a certain part of the hypothalamus in the brain controls the fight-or-flight response.

Stress (chronic) and hormones

  • Stress causes a rise in cortisol and a loss of the circadian release of cortisol. Cortisol makes us less sensitive to leptin, a satiety hormone.

  • Stress causes a rise in epinephrine and norepinephrine levels.

  • Stress causes a decrease in testosterone, estrogen, and progesterone.

  • Stress is associated with lower levels of thyroid hormone.

  • Stress is associated with lower levels of growth hormone.

  • Prolonged stress may lead to insulin resistance.

Stress and the immune system

  • Stress causes impairment of immune system functioning – specifically decreases in secretory IgA, decreases in NK activity, and decreases in IL-2.

  • Stress may enhance humoral immunity at the same time it causes impairment in cell mediated immunity (Ann N Y Acad Sci. 2002. 966. 290-303).

Stress - men versus women (Self Healing. May, 2004. Page 8) 

  • Surveys show that women across all social and economic categories perceive their lives as more stressful than men.

  • Surveys show that sources of stress differ - work is the primary source of stress for men whereas conflict in marriage or problems with other relationships are the primary sources of stress in women.

  • In women there is data that the fight-or-flight response to stress is tempered by the tend-and-befriend response, leading women who are more stressed to be more attentive to their children and to seek out conversations with friends, whereas men who are more stressed tend to isolate themselves. There is an evolutionary basis to this model.

  • The hormonal basis of different stress responses in men versus women may be the release of more oxytocin by women who are stressed, compared with men. Furthermore, testosterone minimizes the effect of oxytocin on social bonding, whereas estrogen enhances this effect.

  • The effect of stress on health often differs - women are more likely to suffer from anxiety, depression, post-traumatic stress disorder, eating disorders, tension headaches, irritable bowel syndrome, and autoimmune disorders, whereas men are more likely to suffer from alcohol abuse, hypertension, or heart disease.

Stress and disease

  • Science has established that people under chronic stress have weak immune systems and have an increased risk of cardiovascular disease.

  • A study in 58 women aged 20-50, with 39 experiencing chronic stress as caregivers of chronically ill children and 19 healthy showed that the women reporting the highest stress levels had changes in blood mononuclear cells (shorter telomeres, less telomerase, higher levels of free radicals) associated with premature aging (Proceedings of the National Academy of Sciences. 2004).

Relaxation Response (Herbert Benson, MD) 

  • The relaxation response is defined physiologically as a state characterized by decreased oxygen consumption, decreased metabolic rate, alpha waves on EEG brainwave tracings, decreased blood lactate levels, decreased respiratory rate, decreased heart rate and decreased blood pressure in those people with hypertension.

  • Hess, in the 1940's, using his electrical stimulation studies in cats, showed that the state which Benson labels as the Relaxation Response is mediated by a specific part of the hypothalamus in the brain. This is an involuntary response with physiology opposite to that of the fight-or-flight response.

  • Meditation is the term that is used for the practice which invokes the relaxation response.

  • Meditation may be defined broadly as any activity that keeps attention pleasantly anchored in the present moment (i.e. intentional self-regulation of present awareness).

  • Meditation allows us through training to activate an involuntary response (i.e. the relaxation response).

  • Two major classes of meditation:

    • Concentration meditation - Focus attention to a single aspect such as breathing, a visual object, or a sound. TM is an example. TM is derived from a Hindu-influenced practice of meditation.

    • Mindfulness meditation - emphasizes detached observation of oneself engaged in a practice such as breathing. Uses a detached observational state to experience all physical and mental events as they occur. Developed as a contemporary system by Jon Kabat-Zinn, PhD. Mindfulness is defined as moment to moment nonjudgemental awareness. Mindfulness meditation is derived from a form of Buddhist meditation known as Vipassana.

  • Contemporary analysis of ancient religious practices such as dovening in Orthodox Jews and chanting in Buddhism shows that these practices elicit the Relaxation Response.

    • We now understand scientifically what our ancestors understood intuitively (i.e. we can learn to activate an "involuntary response" through the practice of a specific technique which is generally labeled as meditation).

    • This is consistent with the finding of Skinner that we can control behavior by altering the environment, and the finding of Miller that we can control involuntary processes through biofeedback - meditation allows us to skip the biofeedback and control involuntary processes through breath awareness.

    • Note that breathing is unique in that it is an involuntary process which can also be easily controlled voluntarily.

  • Four basic elements are necessary in order for one to elicit the Relaxation Response - they are a quiet environment, a mental device such as a sound or a word, a passive attitude, and a comfortable position

  • Meditation allows one to develop the ability to become aware of the Inner Self, which in terms of psychological constructs used to explain the mind, is beyond the ego, and is connected to a larger wholeness

  • Meditation is very safe - the only risks to be aware of include a correlation between prolonged meditation and hallucinations, and a conflict between the passive attitude required to meditate and the free association method used when an individual is undergoing psychoanalysis.

  • Outcomes of meditation:

    • Reduces physiological arousal and psychological anxiety.

    • Cognitive changes – reduction in habitual responses (Altern Ther Health Med. 2005. 11. 42-58).

    • Brain effects- long-term meditators self-induce high-amplitude gamma-band synchrony on EEG tracings (Proc Natl Acad Sci U S A. 2004. 10. 16369-16373).


  • Activation of the sympathetic nervous system via the fight-or-flight response is only one aspect of the effect of stress on our bodies; another is tightening of muscles and resultant muscle tension.

  • Yoga stretches help to alleviate the muscle tension, and also prepare one mentally for meditation.

  • There is some evidence that yoga lowers blood pressure and offers protection from cardiovascular disease (Alt Med Alert. 2005. 8. 92-95).

  • Styles of yoga:

    • Ashtanga – fast-paced series of postures done in a continual flow, similar to tai chi.

    • Bikram – vigorous series of 26 poses that are performed in a room heated to 85 to 100 degrees Fahrenheit.

    • Hatha – uses body postures or poses (asanas) and mindful breathing to develop muscular control, relaxation, and a feeling of wellness.

    • Integral – control of breath, sound vibration, and meditation are emphasized along with the postures; used as a lifestyle intervention by Dean Ornish.

    • Iyengar – uses props to help less flexible students attain the postures and properly flex the spine.

    • Laughter - developed in 1994; combines real and simulated laughter and often results in yogic breathing

    • Viniyoga – flows from pose to pose like ashtanga but is performed at a slower pace.

Behavioral Medicine 

  • Use of cognitive behavioral interventions such as biofeedback, meditation, progressive relaxation techniques, and education on stress management in order to treat conditions such as hypertension and insomnia.

  • Outcomes research is required to determine whether techniques known to alter physiology acutely in highly trained individuals in a laboratory study can in fact induce chronic physiologic changes in selected patient groups.

  • For hypertension, an article published by David Eisenberg, et al. in 1993 in the Annals of Internal Medicine, based upon a review of existing literature, found no significant evidence for benefit of cognitive interventions beyond that of sham techniques or self-monitoring of blood pressure alone.

  • On the other hand, in 1995 a NIH panel concluded based upon a review of published studies that hypnosis and biofeedback are effective in alleviating chronic pain associated with certain cancers, as well as tension headaches, and that relaxation techniques are effective in treating insomnia. Many also consider biofeedback useful in the treatment of Raynaud's, asthma, and stress urinary incontinence.

Placebo Effect (Self-Healing Effect) - belief alone elicits healing. 

  • The placebo effect is based upon the mind affecting the body (in a positive way).

  • Much of the history of medicine is the history of the placebo effect.

  • Rather than simply regarding the placebo effect as a nuisance which interferes with and confounds modern scientific study, practitioners should use the placebo effect as a therapeutic ally (Dr. Andrew Weil). This is part of the art of medicine.

  • Scientific study of the role of faith and belief in healing requires researchers to bridge the gap between the social sciences and the natural sciences.

  • Norman Cousins reminds us that the placebo effect begins with patient confidence in the practitioner, and that the belief of the practitioner is an important factor. When a trusted physician enthusiastically offers a patient a new treatment, the placebo rate may be as high as 70%.


  • Robert Ader, a University of Rochester psychologist, showed in 1974 that the immune system of rats can be classically conditioned. He paired saccharin with cyclophosphamide (an immune depressant drug) and showed that eventually the mere provision of saccharin flavored drinking water to rats led to measurably diminished functioning of the immune system.

  • Researchers at the Ontario Cancer Institute showed that mice conditioned with camphor and an immune stimulant drug called polyinosinicpolycystidilic acid showed increased activity of killer cells, the cells responsible for immune surveillance, in response to mere exposure to camphor.

  • Other researchers in the 1980's demonstrated anatomic evidence of connections between the brain and the immune system, showing that nerve fibers go to the spleen, thymus, lymph nodes, and bone marrow.


  • The hypothalamus in the brain governs the pituitary gland, the master endocrine gland in the body, which is located at the base of the brain, via various neurochemicals.

  • The endocrine system can in turn affect the immune system via endocrine hormones which bind to receptors on the surface of the immune system cells.


  • Defined as the study of the interactions between beliefs, behavioral states, the nervous system, and the immune system.

  • Superimmunity can be defined as the capacity to think and feel in ways that can protect us from disease, heal us, and allow us to attain wellness.

  • We now know that feelings, thoughts, and beliefs can lead to increased or decreased disease susceptibility.


  • In a prospective cohort study of 644 patients with a first acute myocardial infarction (heart attack), higher levels of optimism during the hospitalization were associated with a reduced mortality over 2-decades of follow-up (Am J Cardiol. 2017. 92. 49-56).

  • Post hoc analysis of data in 2389 patients in the RIVER-PCI RCT showed that “in patients with angina, those with more self-reported optimism had better health status outcomes” (Am J Cardiol. 2019. 123. 1399-1405).


  • Simulated laughter can boost mood and sense of psychological well being (Psychol Rep. 2002. 90. 184).

  • Mirthful laughter is associated with immune system benefits (Altern Ther Health Med. 2003. 9[2]. 38-45).

  • Laughter can reduce BP by increasing vascular blood flow (J Womens Health. 2004. 13. 474-479).

  • Laughter can decrease anxiety to a greater extent than exercise (Humor. 2005. 18. 235-246).

  • In a study in 41 rheumatoid arthritis patients and 23 controls, laughter (mirthful laughter) is associated beneficial changes in pro-inflammatory cytokine levels in those with rheumatoid arthritis (Rheumatology. 2006. 45. 182-186).

  • As per a review article with 192 references, current empirical data for the psychological benefits associated with laughter is greater than the data for physiological benefits. The human brain does not distinguish between real and simulated laughter (Altern Ther Health Med. 2010. 16 [6]. 56-64).

  • Mirthful laughter, induced by watching 30 minutes of a comedy was associated with changes in arterial compliance, whereas arterial compliance did not change after watching a documentary for 30 minutes, in a crossover trial design in 17 apparently healthy adults (Am J Cardiol. 2010. 106. 856-859).

  • Sustained laughter in association with the emotion which arises when watching a funny movie or hearing a funny joke has been shown to improve blood flow, lower cortisol levels, and boost immune system function (Time. 9/13/10).

  • Laughter yoga is associated with improvement in symptoms of depression in elderly women, in a RCT (Int J Geriatr Psychiatry. 2011. 26. 322-327).

  • Laughter and humor therapy are beneficial in dialysis patients (Semin Dial. 2014.27. 488-493).

Intriguing Examples of Mind-Body Interactions 

  • Mind creates brain matter - intellectual activity increases dendrite formation in neurons, which may offset loss of neurons with aging.

  • Research subjects trained to smile showed increased levels of endorphins.

  • Students watching a film showing sexual love have increased salivary IgA levels.

  • Exam stress impairs the function of natural killer cells in humans.

  • The lymphocyte response to mitogens becomes sluggish in a person who has lost a spouse, and the death rate for widows and widowers in the first year is ten times that of matched controls.

  • A Harvard Alumni Study has shown that mental health is the most important determinant of physical health.

  • The speed of healing of surgical wounds in the immediate post-operative period is much more rapid in patients who showed faith, trust, and confidence in their doctors, their nurses, and themselves.

  • Patients who are more assertive in the hospital heal faster.

  • Patients recover more quickly in hospital rooms with a view of trees and bushes.

  • Hypnotic suggestion can obliterate the vascular manifestation (induration and erythema) of a positive Manteaux test for tuberculosis, which is a function of cell-mediated immunity. (Hypnosis is an altered state of consciousness characterized by an increased receptiveness to suggestion.)

  • Research shows that determination to overcome illness correlates with greater tolerance to severe pain (Pain is initiated by a physical stimulus and is a protective mechanism; ones emotional response to pain determines how intensively the pain is experienced.).

  • Belly laughter provided increased analgesia for Norman Cousins, a writer stricken with ankylosing spondylitis.

  • DHEA levels rose 100% in 28 people who practiced "Cut Thru" (recognize insecurity, then consciously choose a more hopeful perspective) for 1 month.

  • In a small study (14 couples), amongst those who went through a two session program to learn about stress management and relaxation techniques, 28% conceived in their first attempt at in vitro fertilization, compared to a 6% rate in "historic controls."

  • In Roseto, Pa, the only explanation that could be found for the unusually low heart disease death rate was the strong sense of community.

  • Men with low testosterone levels show a 30% increase following crying. It is fascinating that while tears induced by onions contain only salt and water, tears induced by watching a sad movie contain leftover chemicals secreted when we are under stress. Thus, like our urine and sweat, tears are another "limb" of our excretory system.

  • Five published studies of women desiring larger breasts indicate that imagining larger breasts results in an average increase in circumference over a 12 week period of 1 1/4 inches, and 80% of the increase persists for an additional 12 weeks.

  • Feelings of joy and exhilaration are associated with production of interleukin-2, which costs up to $40,000 per treatment course when used to treat cancer.

  • In a study of 498 older men who completed the MMPI, there was a linear, dose-response relationship between negative emotions and the risk of ischemic heart disease (Am J Card. 2003. 92. 901-906).

Personality Type (trait) and Disease 

  • Some personality types (traits) are associated with physiologic states which predispose to certain disease.

  • Friedman and Rosenman, in the 1950's, found that Type A behavior, characterized by the fierce struggle to do more things in less time against keen competition, is associated with increased risk of heart disease.

  • An analysis of trait anger and trait forgiveness in 308 healthy young female volunteers found “divergent cardiovascular effects of anger and forgiveness, such that anger is associated with a more cardiotoxic and hemodynamic profile, whereas TF (trait forgiveness) is associated with a more cardioprotective profile (Am J Cardiol. 2014. 114. 47-52).

  • In the 1960's, Andrew Weil, MD, writes that the entire medical community acknowledged asthma, rheumatoid arthritis, peptic ulcer disease, and ulcerative colitis to be psychosomatic diseases, but that there has been a shift away from this way of thinking, at least in conventional medical circles.

  • Whether there is a cancer personality remains debatable.

Mind-Body Interactions Which Alter Disease Outcome 

  • Adherence to placebo and health outcomes - in several large placebo controlled studies, in which adherence to placebo was measured, those subjects with a high adherence to taking placebo had better outcomes than those non-adherent with placebo.

    • In the Coronary Drug Project (CDP), a multicenter trial of the cholesterol lowering drugs niacin and clofibrate, clofibrate was no better than placebo with regard to cardiovascular mortality rate; subgroup analysis of those administered clofibrate showed that those who took 80% or more of their pills had only half the death rate of those who did not take their pills.

    • In the BHAT study in 1990, adherence to treatment was associated with a lower mortality rate.

    • In the CHARM study looking at candesartan (Atacand) for CHF, placebo adherence was therapeutically more valuable than the overall statistical treatment difference between placebo and active drug (Lancet. 2005. 366. 2005-2011). The accompanying editorial noted that “high adherence to placebo had a 3.5 times greater effect on reducing mortality than the overall treatment effect of candesartan” (Lancet. 2005. 366. 1989-1991).

  • Support groups and health outcomes

    • In a randomized study involving 86 women with metastatic breast cancer, Dr. David Spiegel, a Stanford psychiatrist, showed that those who participated in weekly discussion groups in which they shared their feelings and learned simple techniques to reduce stress not only had a better quality of life, but nearly doubled their survival to a mean survival of 37 months (Spiegel D, Bloom, JR, Kraemer HC, et al. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet. 1989. 2. 888-891). If new chemotherapy had performed this well, it would have been big news. However, a larger study designed to test the same hypothesis showed only improvements in quality of life, not mortality. This study included 235 patients with metastatic breast cancer and fifty-two 90 minute group sessions of emotional expression, coping, and psychological support. At 6 years, survival in the treatment group was 17.9 months, survival in the control group was 17.6 months (N Engl J Med. 2001. 345. 1719-1726).

    • A study in patients following surgical removal of a malignant melanoma showed that after 5 years, there were only 7 recurrences and 3 deaths in those in a 6 week support group, whereas there were 13 recurrences and 10 deaths in the control group (Arch Gen Psychiat. 1993. 50. 681-689).

  • Learning to increase the capacity for emotional expression, especially anger, may slow the progress of cancer.

  • Interventions that reduce the sense of helplessness/hopelessness may extend life in people with cancer.

  • The Simonton’s have found better outcomes in cancer patients who are able to visualize a strong immune system overcoming weaker cancer.

Clinical Application of Mind-Body Therapies (biofeedback, meditation, relaxation, stress management)

  • There is strong evidence of efficacy for mind-body therapies in the areas of chronic low back pain, headache disorders, insomnia, cardiac rehabilitation, management and treatment of disease-related symptoms in cancer, osteoarthritis, rheumatoid arthritis, and postsurgical outcomes, with moderate evidence of efficacy in the treatment of hypertension (Astin JA et al. Mind-body medicine: state of the science, implications for practice. J Am Board Fam Pract. 2003. 16. 131-147).

  • A study in which four focus groups were conducted, two with medical students and residents, one with primary care doctors, and one with specialists found that barriers to integration of mind-body medicine in clinical practice include inadequate attention to these modalities in medical training, lack of time, inadequate monetary incentives, and a cultural ethos which favors a “quick fix” (Explore. 2005. 1. 278-283).


  • Harvard Mind/Body Institute www.mbmi.org or 1-866-509-0732. Founded in 1988, currently under the direction of Herbert Benson.

  • Heartmath Institute www.heartmath.com Software to display heart rate variability (and demonstrate improvements associated with meditation)

  • Laughter clubs www.laughterclubs.com or 1-800-669-5233

  • Mindfulness Based Stress Reduction Program www.umassmed.edu/cfm/srp or 508-856-2656. Established in 1979, currently under the direction of Jon Kabat-Zinn

  • The Relaxation and Stress Reduction Workbook, 6th Edition. Davis M et al.


  • Benson, Herbert. The Relaxation Response. 1975

  • Benson, Herbert. Beyond the Relaxation Response. 1984

  • Borysenko, Joan. Minding the Body, Mending the Mind. 1987

  • Lipton, Bruce. The Biology of Belief. 2005

  • Pearsall, Paul. Superimmunity. 1987


  • MindBody Medicine. Consumer Reports Books. Edited by Daniel Goleman and Joel Gurin. 1993.


  • Brody H and Miller FG. Commentary: Lessons from Recent Research about the Placebo Effect – From Art to Science. JAMA. 2011; 306 [23]:2612-1613.

  • Ludwig DS and Kabat-Zinn J. Mindfulness in Medicine. JAMA. 2008; 300 [11]:1350-1352.

Updated May 2, 2019