Chapter 11. Mind and Medicine
1. Immune system as the body's brain: Francisco Varela at the Third Mind and Life meeting, Dharamsala, India (Dec. 1990).
2. Chemical messengers between brain and immune system: see Robert Ader et al., Psychoneuroimmunology, 2nd edition (San Diego: Academic Press, 1990).
3. Contact between nerves and immune cells: David Felten et al., "Noradrenergic Sympathetic Innervation of Lymphoid Tissue," Journal of Immunology 135 (1985).
4. Hormones and immune function: B. S. Rabin et al., "Bidirectional Interaction Between the Central Nervous System and the Immune System," Critical Reviews in Immunology 9 (4), (1989), pp. 279-312.
5. Connections between brain and immune system: see, for example, Steven B. Maier et al., "Psychoneuroimmunology," American Psychologist (Dec. 1994).
6. Toxic emotions: Howard Friedman and S. Boothby-Kewley, "The Disease-Prone Personality: A Meta-Analytic View," American Psychologist 42 (1987). This broad analysis of studies used "meta-analysis," in which results from many smaller studies can be combined statistically into one immense study. This allows effects that might not show up in any given study to be detected more easily because of the much larger total number of people being studied.
7. Skeptics argue that the emotional picture linked to higher rates of disease is the profile of the quintessential neurotic—an anxious, depressed, and angry emotional wreck—and that the higher rates of disease they report are due not so much to a medical fact as to a propensity to whine and complain about health problems, exaggerating their seriousness. But Friedman and others argue that the weight of evidence for the emotion-disease link is borne by research in which it is physicians' evaluations of observable signs of illness and medical tests, not patients' complaints, that determine the level of sickness—a more objective basis. Of course, there is the possibility that increased distress is the result of a medical condition, as well as precipitating it; for that reason the most convincing data come from prospective studies in which emotional states are evaluated prior to the onset of disease.
8. Gail Ironson et al., "Effects of Anger on Left Ventricular Ejection Fraction in Coronary Artery Disease," The American Journal of Cardiology 10 1992. Pumping efficiency, sometimes referred to as the "ejection fraction," quantifies the heart's ability to pump blood out of the left ventricle into the arteries; it measures the percentage of blood pumped out of the ventricles with each beat of the heart. In heart disease the drop in pumping efficiency means a weakening of the heart muscle.
9. Of the dozen or so studies of hostility and death from heart disease, some have failed to find a link. But that failure may be due to differences in method, such as using a poor measure of hostility, and to the relative subdety of the effect. For instance, the greatest number of deaths from the hostility effect seem to occur in midlife. If a study fails to track down the causes of death for people during this period, it misses the effect.
10. Hostility and heart disease: Redford Williams, The Trusting Heart (New York: Times Books/Random House, 1989).
11. Peter Kaufman: I interviewed Dr. Kaufman in The New York Times (Sept. 1, 1992).
12. Stanford study of anger and second heart attacks: Carl Thoreson, presented at the International Congress of Behavioral Medicine, Uppsala, Sweden (July 1990).
13. Lynda H. Powell, Emotional Arousal as a Predictor of Long-Term Mortality and Morbidity in Post M.I. Men," Circulation, vol. 82, no. 4, Supplement III, Oct. 1990.
14. Murray A. Mittleman, "Triggering of Myocardial Infarction Onset by Episodes of Anger," Circulation, vol. 89, no. 2 (1994).
15. Suppressing anger raises blood pressure: Robert Levenson, "Can We Control Our Emotions, and How Does Such Control Change an Emotional Episode?" in Richard Davidson and Paul Ekman, eds., Fundamental Questions About Emotions (New York: Oxford University Press, 1995).
16. The angry personal style: I wrote about Redford Williams's research on anger and the heart in The New York Times Good Health Magazine (Kpx. 16, 1989).
17. A 44 percent reduction in second heart attacks: Thoreson, op. cit.
18. Dr. Williams's program for anger controclass="underline" Williams, The Trusting Heart.
19. The worried woman: Timothy Brown et al., "Generalized Anxiety Disorder," in David H. Barlow, ed., Clinical Handbook of Psychological Disorders (New York: Guilford Press, 1993).
20. Stress and metastasis: Bruce McEwen and Eliot Stellar, "Stress and the Individuaclass="underline" Mechanisms Leading to Disease," Archives of Internal Medicine 153 (Sept. 27,1993). The study they are describing is M. Robertson and J. Ritz, "Biology and Clinical Relevance of Human Natural Killer Cells," Blood 76 (1990).
21. There may be multiple reasons why people under stress are more vulnerable to sickness, apart from biological pathways. One might be that the ways people try to soothe their anxiety—for example, smoking, drinking, or bingeing on fatty foods—are in themselves unhealthy. Still another is that constant worry and anxiety can make people lose sleep or forget to comply with medical regimens—such as taking medications—and so prolong illnesses they already have. Most likely, all of these work in tandem to link stress and disease.
22. Stress weakens the immune system: For instance, in the study of medical students facing exam stress, the students had not only a lowered immune control of the herpes virus, but also a decline in the ability of their white blood cells to kill infected cells, as well as an increase in levels of a chemical associated with suppression of immune abilities in lymphocytes, the white blood cells central to the immune response. See Ronald Glaser and Janice Kiecolt-Glaser, "Stress-Associated Depression in Cellular Immunity," Brain, Behavior, and Immunity 1 (1987). But in most such studies showing a weakening of immune defenses with stress, it has not been clear that these levels were low enough to lead to medical risk.
23. Stress and colds: Sheldon Cohen et al, "Psychological Stress and Susceptibility to the Common Cold," New England Journal of Medicine 325 (1991).
24. Daily upsets and infection: Arthur Stone et al., "Secretory IgA as a Measure of Immunocompetence," Journal of Human Stress 13 (1987). In another study, 246 husbands, wives, and children kept daily logs of stresses in their family's life over the course of the flu season. Those who had the most family crises also had the highest rate of flu, as measured both by days with fever and flu antibody levels. See R. D. Clover et al., "Family Functioning and Stress as Predictors of Influenza B Infection," Journal of Family Practice 28 (May 1989).
25. Herpes virus flare-up and stress: a series of studies by Ronald Glaser and Janice Kiecolt-Glaser—e.g., "Psychological Influences on Immunity," American Psychologist A3 (1988). The relationship between stress and herpes activity is so strong that it has been demonstrated in a study of only ten patients, using the actual breaking-out of herpes sores as a measure; the more anxiety, hassles, and stress reported by the patients, the more likely they were to have herpes outbreaks in the following weeks; placid periods in their lives led to dormancy of the herpes. See H. E. Schmidt et al., "Stress as a Precipitating Factor in Subjects With Recurrent Herpes Labialis,"Journal " of Family Practice, 20 (1985).
26. Anxiety in women and heart disease: Carl Thoreson, presented at the International Congress of Behavioral Medicine, Uppsala, Sweden (July 1990). Anxiety may also play a role in making some men more vulnerable to heart disease. In a study at the University of Alabama medical school, 1,123 men and women between the ages of forty-five and seventy-seven were assessed on their emotional profiles. Those men most prone to anxiety and worry in middle age were far more likely than others to have hypertension when tracked down twenty years later. See Abraham Markowitz et al., Journal of the American Medical Association (Nov. 14, 1993).