Please find below existing research papers related to the influence of stress and traumatic life events and the development of cancer and other diseases:
Stressful life events may contribute to breast cancer risk
Psychological stress and the risk of breast cancer: a case–control study
Men's Health More Vulnerable To Stressful Life Events
Do Life Events Precede The Onset Of Heart Attacks?
The association between stressful life events and breast cancer risk: a meta-analysis.
Psychological stress and cancer
Psychological stress linked to cancer
Stressful Life Events and Survival After Breast Cancer
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
Stress and Breast Cancer - research paper - American Cancer Society (PDF)
Stress and Carcinogenesis -research paper (PDF)
Psychological Stress and Cancer Development
Study Finds Link Between Stress, Immune System in Cancer Patients
Adjunctive Psychological Therapy for Cancer
Cortisol, Stress, and Health
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Stressful life events may contribute to breast cancer risk
Life events such as divorce, job loss, relocation, or death in the family are associated with an increased risk of breast cancer, according to a report in the March 1st issue of the American Journal of Epidemiology.
Dr. Kirsi Lillberg, of the University of Helsinki, Finland, and colleagues prospectively examined the association between stressful life events and breast cancer risk in 10,808 women in the Finnish Twin Cohort. The subjects completed self-administered questionnaires on life events and breast cancer risk factors in 1991.
The researchers report that 180 incident cases of breast cancer were identified over 15 years of follow-up. "The multivariable adjusted hazard ratio for breast cancer per one-event increase in the total number of life events was 1.07," they report. When only major life events were considered, the risk estimate rose to 1.35.
Divorce/separation was independently associated with an increased breast cancer risk (hazard ratio = 2.26). An independent association was also observed for death of a husband (hazard ratio = 2.00) and death of a close relative or friend (hazard ratio = 1.36).
"Our data suggest that life events increase breast cancer risk independently of body mass index, weight change, alcohol use, smoking, and physical activity and that their effect is not mediated or modified by self-perceptions of daily stress, adverse personality, or suboptimal mood," Dr. Lillberg and colleagues conclude.
Having adjusted for psychosocial reactions to stress, such as alcohol use, smoking or weight change, the investigators surmise that changes in immunologic function or hormone balance might account for the increase in breast cancer risk.
Am J Epidemiol 2003;157:415-423.
http://www.oncolink.upenn.edu/resources/article.cfm?c=3&s=8&ss=23&
Year=2003&Month=03&id=9448
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Psychological stress and the risk of breast cancer: a case–control study
Objective: To determine whether psychological stress, in the form of past life events and stress at work, was associated with the development of breast cancer.
Methods: The study was based on a case–control study of 257 women with breast cancer operated during 1993–1998 in Szczecin (Poland) hospitals and 565 controls, free of any cancer diagnosis. The subjects were sent a detailed questionnaire including questions on sociodemographic data; lifestyle (lifetime recreational and sport activities, occupational physical activity, diet); reproductive history; experience of psychological stress. The subjects reported major stressful life events, stress of daily activity and experience of stress at work. Logistic regression analyses were used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs).
Results: After adjustment for age and other potential confounders, we found that women with major life events, stress of daily activity, and depression had 3.7 times higher risk for breast cancer, compared to those which did not experience such stress (OR = 3.70; 95% CI, 2.61– 5.26). Women who reported experience of stress at work had a nonsignificant 16% higher risk for breast cancer compared with those who reported no stress (OR = 1.16; 95% CI, 0.82–1.64). A higher proportion of cases (89.1%) than controls (71.1%) reported that their job was stressful, very fretful or very responsible or experienced a major life event (OR = 4.29; 95% CI, 2.66–6.92).
Conclusion: These findings suggest an association between major life events and breast cancer.
Published in Cancer Detection and Prevention 2004; 28(6):399.
Joanna Kruka; Hassan Y. Aboul-Eneinb aInstitute of Physical Education, Faculty of Natural Sciences, University of Szczecin, Al. Piasto´w 40b/6, 71-065 Szczecin, Poland; bPhamaceutical Analysis and Drug Development Laboratory, Biological and Medical Research Department MBC 03-65, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia
http://www.cancerprev.org/Journal/Issues/28/6/4906
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Men's Health More Vulnerable To Stressful Life Events
Although stressful life events may affect the health of both men and women, men are more vulnerable, according to a recent study of nearly 3,000 people in Finland.
The study, published in the September/October issue of Psychosomatic Medicine, looked at whether psychological problems (such as anxiety and mental distress) and health-risk behaviors (such as smoking and alcohol use) underpin the health effects of life events.
Four major life events were studied: the death or serious illness of a family member; being a victim of physical, psychological or sexual violence; severe interpersonal conflict such as divorce; and severe financial difficulties caused by job loss, for example.
"A large body of research suggests that there is a link between stressful life events and later health problems," says the study's lead author, Mika Kivimäki, Ph.D., of the Department of Psychology at the University of Helsinki in Finland. "We found that all the event categories studied were associated with increased psychological problems and impaired health. The death and serious illness of family members … were rated the most severe events."
The study included 2,991 full-time municipal employees who participated in the larger Finnish "8-Town Study," a longitudinal study exploring links between psychosocial factors and health. Twenty-seven percent of the study participants were male and 73 percent were female.
When they entered the study, all of the participants were deemed healthy because they had not taken any sick days from work during 1995. In November 1997, each person was asked about stressful life events, psychological factors and health-risk factors during the previous 12 months. The number of sick days taken from work in 1998 was then used to gauge changes in health. Maternity leave and work absences to care for a sick child were not included in the sick days.
The study results support other research findings suggesting that major life events are associated with increased psychological problems and impaired health.
The results also reinforce previous findings that men are more affected by major life events than women. Among men, as measured by sick days, life events were associated with psychological problems and increased alcohol abuse and smoking, as well subsequent health problems. Among women, however, life events were associated with psychological problems and smoking but not sickness absence.
"Analyses of those who had a stressful event showed smaller social support networks for men than women," the authors write. "Social support might help in coping with life events and thus provide a partial explanation for men's higher vulnerability.
(Center for the Advancement of Health)
http://www.intelihealth.com/IH/ihtIH/WSIHW000/333/342/355756.html
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Do Life Events Precede The Onset Of Heart Attacks?
A group of researchers of the University of Bologna, Italy, (headed by Dr Chiara Rafanelli) has verified in a controlled study whether heart attacks are preceded by stressful life circumstances. The study has been published in the May-June issue of Psychotherapy and Psychosomatics. While the effect of psychological stress and depression on the course of heart disease is commonly recognized, the relationship between recent life events, major depression, depressive symptomatology and the onset of acute coronary heart disease (CHD) has been less considered.
The aim of this study was to investigate the presence of stressful life events, major and minor depression, recurrent depression and demoralization in the year preceding the occurrence of a first acute myocardial infarction (AMI) and/or a first episode of instable angina and to compare stressful life events, also related with mood disorders, in patients and healthy controls. 97 consecutive patients with a first episode of CHD (91 with AMI and 6 with instable angina) and 97 healthy subjects matched for sociodemographic variables were included. All patients were interviewed with Paykel's Interview for Recent Life Events, a semistructured interview for determining the psychiatric diagnosis of mood disorders (DSM-IV), a semistructured interview for demoralization (DCPR).
Patients were assessed while on remission from the acute phase. The time period considered was the year preceding the first episode of CHD and the year before the interview for controls. Patients with acute CHD reported significantly more life events than control subjects (p < 0.001). All categories of events (except entrance events) were significantly more frequent. 30% of patients were identified as suffering from a major depressive disorder; 9% of patients were suffering from minor depression, 20% from demoralization.
Even though there was an overlap between major depression and demoralization (12%), 17% of patients with major depression were not classified as demoralized and 7% of patients with demoralization did not satisfy the criteria for major depression. Independently of mood disorders, patients had a higher (p < 0.001) mean number of life events than controls. With regard to life events, the same significant difference (p < 0.001) compared to controls applied to patients with and without mood disorders.
Our findings emphasize, by means of reliable methodology, the relationship between life events and AMI. These data, together with those regarding traditional cardiac risk factors, may have clinical and prognostic implications to be verified in longitudinal studies.
http://www.karger.com, http://www.alphagalileo.org
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The association between stressful life events and breast cancer risk: a meta-analysis.
Breast cancer is the most prevalent cancer in women in Western societies. Studies examining the relationship between stressful life events and breast cancer risk have produced conflicting results. The purpose of this meta-analysis was to identify studies on this relationship, between 1966 and December 2002, to summarize and quantify the association and to explain the inconsistency in previous results. Summary odds ratios and standard errors were calculated, using random effect meta-regression analyses, for the following categories: stressful life events, death of spouse, death of relative or friend, personal health difficulties, nonpersonal health difficulties, change in marital status, change in financial status and change in environmental status. The presence of publication bias has been explored, and sensitivity analyses were performed to identify heterogeneity, using calculation of the percentage of variability due to heterogeneity, meta-regression analyses and stratification. Only the categories stressful life events (OR = 1.77, 95% CI 1.31-2.40), death of spouse (OR = 1.37, 95% CI 1.10-1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09-1.68) showed a statistically significant effect. Publication bias was identified in both stressful life events (p = 0.00) and death of relative or friend (p = 0.02). Sensitivity analyses resulted in the identification of heterogeneity in all categories, except death of spouse.
The results of this meta-analysis do not support an overall association between stressful life events and breast cancer risk. Only a modest association could be identified between death of spouse and breast cancer risk.
Int J Cancer. 2003; 107(6):1023-9 (ISSN: 0020-7136)
Duijts SF; Zeegers MP; Borne BV, Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
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Psychological Stress and Cancer
The complex relationship between physical and psychological health is not well understood. Scientists know that many types of stress activate the body's endocrine (hormone) system, which in turn can cause changes in the immune system, the body's defense against infection and disease (including cancer). However, the immune system is a highly specialized network whose activity is affected not only by stress but by a number of other factors. It has not been shown that stress-induced changes in the immune system directly cause cancer.
Some studies have indicated an increased incidence of early death, including cancer death, among people who have experienced the recent loss of a spouse or other loved one. However, most cancers have been developing for many years and are diagnosed only after they have been growing in the body for a long time (from 2 to 30 years). This fact argues against an association between the death of a loved one and the triggering of cancer.
The relationship between breast cancer and stress has received particular attention. Some studies of women with breast cancer have shown significantly higher rates of this disease among those women who experienced traumatic life events and losses within several years before their diagnosis. Although studies have shown that stress factors (such as death of a spouse, social isolation, and medical school examinations) alter the way the immune system functions, they have not provided scientific evidence of a direct cause-and-effect relationship between these immune system changes and the development of cancer. One NCI-sponsored study suggests that there is no important association between stressful life events, such as the death of a loved one or divorce, and breast cancer risk.* However, more research to find if there is a relationship between psychological stress and the transformation of normal cells into cancerous cells is needed.
One area that is currently being studied is the effect of stress on women already diagnosed with breast cancer. These studies are looking at whether stress reduction can improve the immune response and possibly slow cancer progression. Researchers are doing this by determining whether women with breast cancer who are in support groups have better survival rates than those not in support groups.
Many factors come into play when determining the relationship between stress and cancer. At present, the relationship between psychological stress and cancer occurrence or progression has not been scientifically proven. However, stress reduction is of benefit for many other health reasons.
*"Self-Reported Stress and Risk of Breast Cancer," Felicia D. Roberts, Polly A. Newcomb, Amy Trentham-Dietz, and Barry E. Storer. Cancer, March 15, 1996.
"Stress and Immune Responses After Surgical Treatment for Regional Breast Cancer," Barbara L. Andersen, William B. Farrar, Deanna Golden-Kreutz, et al. Journal of the National Cancer Institute, January 7, 1998.
http://www.monitor.net/monitor/8-19-95/stress.html
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Psychological stress linked to cancer - research results
As if the sagging economy and rush-hour commuting weren't stressful enough, here comes a provocative pair of studies to add to your worries. They indicate that psychological stress may increase an individual's risk of developing certain cancers.
Two years ago, Australian researchers reported that stressed-out individuals might face an increased risk of colorectal cancers -- malignancies that each year strike an estimated 152,000 people in the United States alone. Hoping to verify that link, Joseph G. Courtney of the University of California, Los Angeles (UCLA), School of Public Health and his co-workers joined forces with researchers in Sweden who had access to a large database on Stockholm-area patients with colorectal cancer.
The researchers recruited 569 of these men and women for their study, along with 510 randomly selected cancer-free adults. Each of the study's participants then answered a series of questions about stressful events.
In the September EPIDEMIOLOGY, Courtney's team now confirms that severe on-the-job aggravation appears to put people at increased risk of developing colon and rectal cancers. Those who reported a history of workplace problems over the past 10 years faced 5.5 times the colorectal-cancer risk of adults who reported no such problems.
That association held even after the researchers accounted for diet and other factors that had previously been linked to these malignancies. Unpublished research by the UCLA team also hints that individuals who toil in high-pressure situations while processing little or no control over workplace decisions face the highest risks.
In a second new study, Japanese researchers report finding cellular changes in psychologically stressed animals that may explain how anxiety might foster cancer.
For their investigations, Shuichi Adachi and his co-workers at Saitama Medical School in Moroyama caged sets of 30 young rats in a "communications box." The box is laid out like a checkerboard, with half the rodents -- those in the chambers corresponding to the red squares, for instance -- receiving periodic electrical shocks over a 5- to 10-hour period. The study then monitored how nonshocked animals, in cages corresponding to the black squares, responded biochemically to the psychological stress induced by watching, listening to, and smelling the torment of their neighbors.
In terms of the amount of altered DNA in their tissues, non-shocked rats that had completed one day of tests were no different from animals that had never participated in the psychological testing. But non-shocked rats that endured two to four days of such tests developed sharply elevated concentrations of 8-hydroxy-2'-deoxyguanosine in the DNA of their livers.
This oxidative change, known as a DNA lesion, occurs spontaneously in the target organs of animals exposed to carcinogens, radiation, or an overabundance of free radicals -- biologically damaging chemical agents possessing one or more unpaired electrons.
The stress-induced increase in the number of lesions in liver DNA "must be interpreted as [caused by] excess generation of reactive oxygen species," Adachi's team concludes in the Sept. 15 CANCER RESEARCH. As such, they report, it constitutes "the first evidence that oxidative damage to nuclear DNA is induced by psychological stress."
The rats appeared to be able to repair most of the stress-induced lesions within an hour. However, numerous studies have shown that as animals age, they tend to accumulate such oxidative lesions in their DNA. And in the Sept. 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, Bruce N. Ames and his co-workers at the University of California, Berkeley, review the cancer significance of those lesions. If present when a cell divides, they note, "an unrepaired DNA lesion can give rise to a mutation" -- and ultimately a malignancy.
Nor is the liver the only organ vulnerable to stress-mediated cancers, Adachi's team reports. The Saitama researchers note that mice psychologically stressed every other day for four months proved more susceptible to urethane-induced lung tumors than unstressed animals exposed to this carcinogen.
The Japanese study offers a "superior model" of psychological stress in humans, Courtney told SCIENCE NEWS.
Scientists know that stress can trigger the body's "fight-or-flight" response, in which the adrenal glands churn out powerful hormones that divert blood flow from internal organs (such as the intestines or liver) to the brain, muscles, and heart. Once the danger subsidies, blood rushes back into the oxygen-starved internal organs, Courtney says. That burst of oxygen-rich blood may lead to increased production of free radicals -- and DNA lesions.
In addition, stress weakens the immune response, Courtney says. A vigorous immune response should kill damaged cells. However, if the immune system is compromised, a malignant cell might escape, spawning a tumor, he suggests.
COPYRIGHT 1993 Science Service, Inc.
COPYRIGHT 2004 Gale Group
http://www.findarticles.com/p/articles/mi_m1200/is_n13_v144/ai_14491697
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Stressful Life Events and Survival After Breast Cancer
OBJECTIVE: This study assessed the relation of stressful life events with survival after breast cancer.
METHODS: This study was based on women with histologically confirmed, newly diagnosed, localized or regional stage breast cancer first treated in 1 of 11 Quebec City (Canada) hospitals from 1982 through 1984. Among 765 eligible patients, 673 (88%) were interviewed 3 to 6 months after diagnosis about the number and perceived impact of stressful events in the 5 years before diagnosis. Three scores were calculated: number of events; number weighted by reported impact; and for almost 80% of events, number weighted by community-derived values reflecting adjustment required by the event. Scores were divided into quartiles to assess possible dose-response relationships. Survival was assessed in 1993. Hazard ratios and 95% confidence intervals (CIs) comparing all-cause and breast cancer–specific mortality were calculated with adjustment for age, presence of invaded axillary nodes, adjuvant radiotherapy, and systemic therapy (ie, chemotherapy and hormone therapy).
RESULTS: When quartiles 2, 3, and 4 were compared with the appropriate lowest quartile, adjusted hazard ratios for all-cause mortality were 0.99 (CI = 0.70–1.38), 0.97 (CI = 0.73–1.31), and 1.04 (CI = 0.78–1.40) for number, number weighted by impact, and number weighted by community-derived values, respectively. Results were essentially similar for the relation between stressful life events limited to those occurring within the 12 months before diagnosis and overall mortality and between stressful life events in the 5 years before diagnosis and breast cancer–specific mortality.
CONCLUSIONS: Stress was conceptualized as life events presumed to be negative, undesirable, or to require adjustment by the person confronting them. We found no evidence indicating that this kind of stress during the 5 years before diagnosis negatively affected survival among women with non-metastatic breast cancer. Evidence from this study and others on the lack of effect of this type of stress on survival may be reassuring for women living with breast cancer.
Elizabeth Maunsell, PhD, Jacques Brisson, MD, ScD, Myrto Mondor, MSc, René Verreault, MD, PhD and Luc Deschênes, MD, FRCSC
From the Epidemiology Research Group (E.M., J.B., M.M., L.D.), Department of Social and Preventive Medicine (E.M., J.B., M.M., R.V.), and Department of Surgery (L.D.), Université Laval, Québec, Québec, Canada.
Address reprint requests to: Dr. E. Maunsell, Groupe de recherche en épidémiologie, Centre de recherche, Pavillon St-Sacrement, 1050 chemin Ste-For, Québec, QC, Canada, G1S 4L8.
http://www.psychosomaticmedicine.org/cgi/content/full/63/2/306
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Causal Relationship Between Stressful Life Events and the Onset of Major Depression
OBJECTIVE: Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression.
METHOD: The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent's behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis.
RESULTS: While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs.
CONCLUSIONS: Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is non-causal, since individuals predisposed to major depression select themselves into high-risk environments.
Kenneth S. Kendler, M.D., Laura M. Karkowski, Ph.D. and Carol A. Prescott, Ph.D.
http://ajp.psychiatryonline.org/cgi/content/abstract/156/6/837
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Psychological Stress and Cancer Development
A number of studies have indicated that there is a positive correlation between stress and cancer development as well as progression. Results indicated that an extensive longitudinal study is needed in order to definitively conclude that stress has a direct effect on cancer development in humans.
Researchers have determined that when an individual is experiencing stress, physical changes occur within the body. During a stressful situation, "the hypothalamus activates the pituitary gland, which in turn activates the adrenal glands to produce hormones that cause chemical changes in various cells and tissues" (Benson & Stuart, 1992, p. 324). This process is called the fight-flight response. During this fight-flight response, the immune system can become suppressed. The suppression of the immune system leads to susceptibility to diseases, including cancer. Conversely, it has been demonstrated that positive messages from the brain can enhance the ability of the immune system to stave off disease. This mind body connection is referred to as psychoneuroimmunology (PNI).
PNI research began in the 1960s. Today’s researchers have become progressively more sophisticated. PNI Researchers examine how psychosocial factors such as optimism and social support moderate stress responses. "They are mapping the biological and cellular mechanisms by which stress affects the immune system, and they are testing new theories, such as the idea that the immune system acts as a "sixth sense" that gives the brain valuable information about a person's health status" (DeAngelis, 2002).
One of the newest theories of PNI is called the bidirectional model. It states that there is a link from the immune system to the brain and not the other way around. According to this theory the immune system is a messenger that signals the brain to infection or injury by releasing proteins called proinflammatory cytokines. These cytokines travel to the central nervous system and brain to communicate information about the body's distress. Next, "the brain releases its own cytokines that signal the central nervous system to initiate a surge of responses such as fever and listlessness that, theorists believe, help the body adapt by reducing energy output" (DeAngelis, 2002). PNI researchers are interested in cytokines because they epitomize an immune response gone wrong. Stress increases hormones, which slow the delivery of cytokines to the site of injury or infection.
In the past decade, psychobiologist Shamgar Ben-Eliyahu has been working on the link between stress and tumor development. Ben-Eliyahu and his colleagues discovered that stress such as "forced swim, surgery, and social confrontation decreases lymphocyte activity in rats for as little as one hour and as long as a day or two" (Azar, 1999). These types of stresses also cause a two-to-five-fold increase in certain types of tumors. These stresses also advance tumor growth.
Emory University psychologist Jay Weiss found evidence that b-lymphocytes (the type of white blood cell that responds to an antigen by producing antibodies) are involved in combating tumor cells in the lungs of rats. According to Weiss, b-lymphocytes are the immune cells that are most influenced by stress.
Another study investigated the possibility that stress could weaken one part of the DNA repair process. Forty-five rats were given dimethlynitrosamine (a carcinogen), and half were assigned to a stress condition. The methyltransferase, a DNA repair enzyme generated in reaction to carcinogen damage, was drastically reduced in stressed animals’ splenic lymphocytes, as compared with splenic lymphocytes obtained from the control rats (Kielcot-Glaser & Glaser, 1999).
Experiments on immune system suppression and psychological stress are not limited to lab rats. Janice K. Kiecolt-Glaser and her colleagues conducted a series of experiments on medical students in 1985. "Glaser and her colleagues documented that commonplace stressful events resulted in immune suppression as detected in students’ blood samples taken during examinations as compared to similar samples taken one month previously" (Dacher, 1991, p. 22).
Bereaved spouses are another example of stress and immune system suppression. "Bereaved spouses, and most particularly widowers, are significantly more vulnerable to disease than the unbereaved" (Pearsall, 1987, p. 104). Lymphocyte responsiveness (the effectiveness of the part of the immune system that fights disease by maintaining homeostasis and preventing over production of cells) decelerates in a person who has lost a partner. When these lymphocytes were stimulated with mitogens (a substance that induces mitosis, or cell reproduction) they reproduced at a significantly lower rate than those of individuals who had not lost a significant person in their lives" (Pearsall, 1987, p. 104).
It is a known fact that lymphocytes have minute receptors on their surface intended for the reception of a range of secretions from the brain so that they can operate in response to the brain’s signals. It is possible that the loss of daily interactions and closeness can cause the brain to signal the body cells to develop more rapidly than normal in order to fill that void of activity. This would make the lymphocytes less effective due to the chemical changes, which hinder the response at receptor sites. This causes cell disease to begin. This theory of cell disease is called surveillance theory of cancer (Pearsall, 1987). This theory holds that cancer cells are constantly developing in the body, but that the immune system’s ability to recognize them as abnormal and destroy them are what prevents them from becoming malignant tumors. When the number of cancer cells becomes too large to be destroyed or when the lymphocytes become suppressed is when carcinogenesis occurs.
Another theory of cancer development and stress involves something called the Type C personality. Just as the Type A personality tends to develop heart problems, the Type C personality tends to develop cancer. Lydia Temoshok, a psychologist, and her graduate student, Andrew Kneier, conducted a study at the University of California. Temoshok and Kneier compared the responses of patients with malignant melanoma and patients with cardiovascular disease to receiving mild electrical shocks. "The patients with malignant melanoma had a stronger physical reaction to the test, but tended to downplay how emotionally upset they were about it when they talked to the researchers afterward" (Goleman & Gurin, 1993, p. 88). Temoshok coined the term Type C personality with characteristics like suppression of strong emotions, compliance with the wishes of others and a lack of assertiveness, avoidance of conflict, etc. (Martin, 1997).
In the 1960s, Ronald Grossarth-Maticek started a long-term prospective study of 1,353 Yugoslavian villagers. He learned that the villagers who scored highly on measures of anti-emotionality and rationality were at the most risk for developing cancer. Hans Eysenck worked with Grossarth-Maticek and discovered that personality variables and psychological stress have an important connection with the risk of dying from cancer years later.
Although there are many theories regarding stress and the development of cancer, they have not been proven. The Type C personality, for example, may not be the cause of cancer but the result of having an upsetting disease.
People diagnosed with cancer experience dramatic emotional changes. It is extremely difficult to link behavior and psychological stress to physical changes that influence tumor progression due to the fact that patients receive treatments that can alter any or all of these factors. For example, the side effects of chemotherapy can be immuno-suppression.
The stress an individual feels may not necessarily be directly manifested in the development of cancer. It is possible that stress leads to poor lifestyle choices that result in the occurrence of cancer (Goleman & Gurin, 1993). Stress, attitudes, and beliefs can affect lifestyle choices and health-related behavior. For example, an individual under stress may smoke cigarettes or drink alcohol. These behaviors have been proven to increase the risk of cancer. Other health-related behaviors have been correlated with cancer. For example, one-third of all cases of cancer can be attributed to poor diet.
Another current theory about psychological and cognitive states and cancer development suggests that certain negative emotional states (such as depression) may have evolved as part of the sickness response to conserve energy during times of infection.
There is a new theory that is challenging Hans Selye’s General Adaptation Syndrome theory (GAS). Selye believed that everyone goes through the same set of hormonal and immune system changes. This new theory suggests that there are two stress reactions. One reaction is the typical fight-flight response, but the other reaction is of withdrawal. This withdrawal reaction conserves energy. These reactions have been demonstrated using animals.
Another problem with researching stress and tumor growth in humans is that researchers cannot expose humans to tumor cells as they can with animals (Azar, 1999). Researchers often have to interview people with cancer in regards to their stress levels before their diagnosis. The interview style of data collection could lead to inaccurate self-report. A person who is now living with cancer and its treatments may look back at their life before the diagnosis and think, in comparison, that it was much more stress free.
A large longitudinal study is necessary to ultimately establish the correlation between psychological stress and carcinogenesis. A reliable study should include a sufficient number of healthy participants. The study should monitor them for about twenty years. A psychological assessment should be done periodically throughout the twenty-year span. The psychological assessment would determine the stress levels of the individuals throughout the study. This type of longitudinal study will allow researchers to see who develops cancer, who will survive it, and who will not develop cancer over time.
Excerpts from the research paper STRESS AND CARCINOGENESIS, 4/30/03, The Link Between Psychological Stress and Carcinogenesis from Jennifer V. Stivers
References
Armandola, E.A. (2002). "Psycho-oncology and cancer: sifting through the evidence". April 25, 2003, medscape.com.
Azar, B. (1999). Probing links between stress, cancer. APA, Monitor, 30(6).
Benson, H., & Stuart, E.M. (1992). The wellness book: the comprehensive guide to maintaining health and treating stressrelated illness (pp. 323-324). New York, NY: Birch Lane Press.
DeAngelis, T. (2002). A bright future for PNI. APA Monitor, 33(6).
Dacher, E.S. (1991). PNI: Psychoneuroimmunology the new mind/body healing program (pp. 22; 71-73). New York, NY: Paragon House.
Diurnal,D., Sephton S.E., Sapolsky, R.M., Kraemer, H.C.,& Speigel, D. Cortisol rhythm as a predictor of breast cancer survival. (2000). Journal of the National Cancer Institute 92(12), 994-1000.
Kielcot-Glaser, J.K., & Glaser (1999). Psychoneuroimmunology and cancer: fact or fiction? European Journal of Cancer, 35(11), 1603-1607.
Goleman, D., & Gurin, J. (Eds.). (1993). Mind body medicine: how to use your mind for better health (pp. 87-88). Yonkers, NY: A Division of Consumers Union.
Martin, P. (1997). The healing mind: the vital links between brain and behavior, immunity and disease (pp. 228-229). New York, NY: St. Martin’s Press.
Pearsall, P. (1987). Superimmunity: master your emotions & improve your health (pp. 103-105). New York, NY: Mc-Graw-Hill Book Company.
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Study Finds Link Between Stress, Immune System in Cancer Patients
Breast cancer patients who feel high levels of stress concerning their diagnosis and treatment show evidence of a weakened immune system compared to patients experiencing less stress, a new preliminary study shows.
Researchers found that the highly stressed women had lower levels of natural killer cells than women who reported less stress. Natural killer cells are one vital weapon making up the immune system.
"Natural killer cells have an extremely important function with regard to cancer because they are capable of detecting and killing cancer cells," said Barbara Andersen, leader of the research team and professor of psychology and obstetrics and gynecology at Ohio State University.
"These results, although preliminary, suggest that psychological stress may play a role in how the immune system responds to cancer."
Andersen presented the results August 13 in New York at the annual meeting of the American Psychological Association.
These results are the initial findings of an ongoing study that will examine the relationship between stress, immunity and breast cancer. The study will involve more than 200 women with breast cancer who are being treated at the Arthur G. James Cancer Hospital and Research Institute at Ohio State or by collaborating physicians in the Columbus area.
The women entered the study within one to two weeks of surgical treatment and before they began any additional therapy. The women completed questionnaires that examined signs of stress such as intrusive thoughts about the disease and attempts to avoid thinking or talking about it.
The results are consistent with other studies that have found links between stress and immune function in relatively healthy individuals. "We're showing that the same relationship between stress and immune function occurs in people with cancer," Andersen said.
Researchers want to examine whether psychological interventions can reduce stress in these cancer patients, improve immune function, and possibly even extend patient survival.
"It's clear from previous research that psychological interventions can improve the quality of life for cancer patients," she said. "The question is whether such interventions can have biological or health consequences."
Some of the interventions that will be tested in the patients include progressive muscle relaxation, training in problem solving, and use of social support. Patients will also get information about healthy diets, exercise and disease treatments and learn assertive communication skills for dealing with health care providers.
Andersen said the stability of many cancer mortality rates makes it important to find innovative treatments to improve the quality of life of cancer patients. Psychological techniques can play a role.
"Psychological interventions might not only have important roles in reducing stress and improving quality of life, but also in extending survival. We need to examine this possibility more closely," she said.
Jeff Grabmeier writes for Ohio State University.
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Adjunctive Psychological Therapy for Cancer
Introduction
Since our topic is "stress and cancer," we need first to discuss what this means. "Stress" has been a confusing term in biomedicine because it evokes images of a weight distorting a beam or other mechanical analogues. In fact, the term was introduced by Hans Selye and HG Wolff to indicate "a state of the living creature that results from noxious stimuli or circumstances, and not to refer to the stimuli themselves." That is, stress is a reaction, not an environmental condition and, as such, depends on the intrinsic nature and past experiences of the organism experiencing these conditions.1,2
We have all observed how a "heavy load" to one person may be a trivial challenge to another. As Shakespeare puts it in Hamlet, "There is nothing either good or bad, but thinking makes it so." In the medical context, Lazarus and Folkman 3 offer a commonly accepted definition: "a psychological stress response occurs when the demands imposed by events exceed a person's ability to cope." This is a state we often see in cancer patients.
How Could the Mind Affect Cancer?
How could such an apparently intangible thing as a psychological stress reaction affect a concrete entity like a cancer? This is the venerable mind-body problem, always a puzzle to biomedicine, restated in the cancer context. I will return to a brief look at ways of conceptualizing the mind-body relationship at the end of this paper, but now draw attention to Figure 1, which describes the broad pathway of possible events connecting mental state to cancer outcome.
Psychological reactions to external stimuli exert an effect on the general physiology of the body through two routes. The first is an "external loop," that is, via behaviours such as smoking and diet, which are known to influence cancer incidence and might affect progression via such behaviours as seeking or avoiding medical treatment. The second is an "internal loop," the effects of emotional states, triggered by thoughts, via neuroendocrine intermediaries, on a variety of target organs. The pituitary-adrenal axis is perhaps the most well known of these pathways. This loop might affect both incidence and progression of the disease. It follows that the "stress-cancer" title makes little sense: we are interested in a pathway, or number of pathways, through which environmental stimuli, via the mind, might affect the internal milieu that regulates or fails to regulate cancer growth.
Evidence for a Mind-Cancer Link
There is a long history of attempts to show a contribution of mind to disease pathogenesis generally, although there seems to be a gradual increase in willingness to acknowledge a role for mind.4-6 In the cancer field, while the "external loop" has been well studied, the role of an "internal loop" is still controversial. The older evidence has been reviewed elsewhere.7 It is of three main kinds: attempts to correlate "personality" with cancer incidence and prognosis, which is reviewed and brought up to date by Dr. Fox in the following paper, experimental manipulations of animals bearing tumors and attempts to show that psychological therapy can influence the course of cancer.
In the animal cancer field there is general agreement that mental state can affect cancer growth, in at least some experimental models. The following example shows the sophistication that has been achieved.8 Mice bearing transplanted tumor cells were subjected to repeated short bursts of electric shock. This stress reproducibly caused faster growth of the tumor and earlier death of the animals. The possible "psychological" effects of the shock could be dissociated from its physical impact using a "yoked control" design.
Some of the mice were put in cages from which they could escape the shock by moving into another compartment. Each of these animals was paired with another mouse that could not escape by such voluntary action, but in whose cage the shock was also turned off by the escape of the first mouse. Thus a comparison could be made between sets of two subjects, both of whom received exactly the same physical stressor, but only one of whom had the power to exert some control over it. The finding was that the tumor grew faster, and animals died earlier, in the group with no control. By contrast, having control virtually eliminated the tumor-promoting effects of the electric shock. These interesting results have since been confirmed by other workers.
Reasons for Interest in the Possible Effects of Mind on Human Cancer (Internal Loop)
Considerable epidemiologic effort is currently being devoted to understanding the effects of mind on cancer via the external (behavioral) loop. My interest lies in the internal pathway, which has been relatively neglected to date, since it is considerably less open to inspection. There are three main reasons for this interest.
While the external loop involves factors that are largely relevant to cancer incidence, the internal path is also potentially important for cancer progression in people who already have the disease. There is enough evidence, both clinical/anecdotal and experimental, to suggest the possibility that more subtle psychological events influence the progress of cancer. It may therefore be possible to develop an adjunctive approach to cancer therapy through this route.
The idea that mental "attitude," that is, a combination of thoughts, emotions and unconscious mental attributes, may affect health has potentially wide ramifications. If it is true for cancer, it probably holds for many other diseases. Unfortunately, the waters have been muddied by frequent, exaggerated claims in the "New Age" literature.
The question of mind affecting health bears also on the wider philosophical issue of the extent to which we "create" our own reality through our mental processes. A demonstration of mind strongly affecting health would contrast sharply with the materialistic views currently in vogue and might have the potential to enlarge our appreciation of our relationship to the world in areas far beyond health.
Possible Experimental Approaches: The Effects of Psychological Intervention
Complete understanding of the mind-cancer link requires elucidation of many steps on a lengthy pathway. We might be tempted first to investigate the physiological mechanisms that presumably exert some control over cancer growth and then to see whether mental change could influence them. After decades of research there is still little understanding of the nature of these regulators.
An alternate strategy is to view the pathway as a "black box" and test whether mental change, induced by psychotherapy, can affect ultimate outcome, either tumor growth rate or survival. Table 1 lists the published studies of this kind. They fall into three categories. There are a number of anecdotal reports of cancer patients living beyond the expected time, or even showing remission of disease, while receiving psychological help.9-11 These studies either have no controls or use only historical controls, under conditions where selection bias is not ruled out; where remissions were seen, there was little documentation.11 Thus, while the work is of some interest to the clinician, it does not rate as epidemiologic evidence.
The second group comprises two case-control studies, the first a small trial of the effect of supportive therapy on life span of breast cancer patients, which showed no effect,12,13 and the second a larger study that at first claimed a survival advantage to controls.14 The conclusion was later retracted when the matching was discovered to be biased.15
The third group in Table 1 includes two well-designed, although small, randomized trials showing a life-prolonging effect of psychological interventions. These interventions were very different. In the Fawzy study,16 a six-session supportive and behavioral group program was given to patients with stage 1 malignant melanoma; recipients were significantly less likely to have died, compared with untreated controls, at analysis six years later. In the Spiegel study,17 one year of weekly supportive group therapy for women with metastatic breast cancer doubled the average survival from study entry compared with untreated controls.
Of the remaining three studies, the Grossarth-Maticek work 18 also gave a positive result, but the data handling has been shown by Fox 19 and others to be unreliable; the Linn study 20 showed no effect of a relatively trivial individual intervention (brief counseling) for late-stage patients; and the Ilnyckyj 21 trial demonstrated no survival advantage to patients who had received variable amounts of group counseling. It is doubtful, however, that this last study had the necessary power to detect an effect, since the patients were heterogeneous with respect to disease and stage, and the control and intervention cells quite small (approximately 30).
Thus we have an interesting state of affairs, with the two methodologically best studies of this kind claiming a positive effect, and only weak contrary evidence. More trials are needed: two are currently in progress in Toronto (Cunningham et al. and Goodwin et al.), and at least one other in the USA (Spiegel, Morrow et al., personal communication). A likely situation in five to eight years' time is that we will have results from several more trials, some of them supporting a life-sparing effect of psychological help, and some not. While meta-analysis may help adjudicate this issue, it seems unlikely that the picture will be clear enough to allow a decision on whether or not to add psychological help routinely to medical clinical practice. How, then, are we to decide whether there really is an effect of mental change on cancer progress?
Does Psychological Change Accompany Physical Change?
Our confidence in a mind-cancer relationship would be greatly increased if we could correlate intrapsychic change with beneficial physical (anticancer) effects, that is, if we could show that psychotherapy produces psychological changes in concert with, say, prolongation of life. There is good evidence that psychological interventions improve quality of life (QL),22 and there is correlative evidence linking quality of life with better survival.23,24
It is not known whether the relationship between QL and survival is causal; we cannot, therefore, draw the conclusion that improving QL will necessarily prolong life, although this seems a reasonable hypothesis. An analysis of the relation between change in QL and survival would strengthen this connection and could probably be done with data from the existing studies. In one of our own studies,25 participants were randomized either to brief support plus training in specific coping skills or to support alone. The data showed that both interventions caused significant improvement over baseline values on two measures of QL, although the psychological training had the greater effect.
The Need to Measure Change, Not Static State
A brief digression is needed here to emphasize the need for longitudinal rather than cross-sectional studies in relating mental state, whether quality of life or personality or other attributes, to disease progression. This is because cancer evolves, often over years, to accommodate to the milieu provided by the host. By the time it is detectable, its "life span" is almost over. A cross-sectional measure attempting to correlate personality, for example, to disease progression 26 is almost bound to show little relationship because the cancer is perfectly adapted to that host. It is necessary to attempt to relate change in mental qualities to course of disease in order to test the hypothesis.
A More "Fine-grained" Analysis of the Relationship between Mental State and Cancer Progression
We will not feel we really understand this connection, if it exists, until we have a much finer analysis of the events occurring in the minds of patients and how this relates to physical outcome. In other words, we need to focus on the part of the "internal loop" illustrated in Figure 2. There is at least a potential for relatively fine measurement of what is happening in the "psychological responses" box in this figure: human psychological processes are, of course, highly complex, and many different states can be discriminated. The drawback is that this has to be done with imprecise tools, subject self-report and observer rating. Quantification is difficult. An advantage is that findings can be translated immediately into therapeutic tools designed to move the subjects towards a state that seems to have survival advantage. For example, if spiritual awareness correlates highly with better prognosis, methods like meditation can be taught to promote this state of mind.
A prospective, correlative design would seem to be needed: providing psychological treatment to a number of cancer patients, then following them simultaneously with psychological and physical measurements. The principal difficulty with this approach is to find a physical endpoint that is not influenced by many confounding factors. Survival time as an endpoint suffers from this disadvantage; it is very variable even within a single diagnostic category.
One solution might be to measure tumor remission in patients with measurable tumors who are not receiving any confounding medical treatment. Because of the rarity of "spontaneous remission," any cases demonstrating it could reasonably be assumed to have profited from the psychological help. Some patients with metastatic melanoma, kidney carcinoma or colorectal cancer, who are often untreated for long periods, could be recruited. The psychological assessments could be as varied as resources allow, but would probably include self-report questionnaires, observer ratings (at interviews), behavioral observations (of amounts of homework assignments done, for example) and qualitative analyses of interview transcripts.
A New Conceptual Approach to the Mind-Health Relationship
Ultimately, I believe we need a new conceptual approach to relate mental state to cancer, or health generally, with any reliability. This is because existing psychological constructs do not seem to capture adequately the important relationships: researchers in this field usually employ a pastiche of measures, often designed to assess mental health, each of which captures very little of the variance in physical health status. One promising avenue is what may be called the "biosemiotic" approach, which involves focusing on information transmission rather than only on material structures.27-29
The left side of Figure 3 shows the familiar hierarchical arrangement of structures within a human being, extending out to the larger societal and worldly structures in which she/he is embedded. It will be seen that these terms refer to material entities. On the right-hand side of the figure is a list of examples of "informational" terms, representing not "things" but the patterns that characterize them. These patterns, rather than the underlying substance, are often what interests us most; for example, the physical composition of DNA is relatively simple, but the way in which its four base pairs are arranged provides the information on which life is largely based.
Similarly, "mind" is a pattern or informational term, corresponding roughly to the structure of the brain. It is the software, so to speak, while the neurology is the hardware of our inner computer. These two columns are different "languages," and much confusion has arisen because of the failure to recognize that mind is a pattern term, while brain and body are material terms. The organism can clearly be influenced by information just as surely as by a material force.
Several consequences follow from this. We may develop theories that are framed in informational language, rather than in the familiar mechanistic terms. An example would be the idea that health depends on optimal flow of information or "connectedness" between all the levels of the organism.28 This is something that we can measure, at least in principle, by measuring, for example, the extent of an individual's awareness of body tension or of unconscious processes or of connection to other people (in a subjective sense rather than as a number of contacts).
Another corollary of the view of the person as a hierarchical arrangement of both structural and informational levels is that we can see the invalidity of the conventional "pie chart" method of dividing up the factors that influence a disease like cancer. It is common to make a single pie combining dietary, smoking, genetic and other factors, and then to claim that there is little or no "room" left for psychological determinants.30 In fact, these factors are not independent.
A more accurate model would be a "stack of pies," all of the variance in cancer incidence and causation being explicable, in principle at least, at all levels.31 We can see how different levels vary simultaneously if we ask ourselves: Does the known, overwhelming contribution of smoking to lung cancer exclude significant contribution of biochemical factors, like damage to DNA, or of cellular factors? Obviously all operate at the same time. Similarly, even a genetic lesion, for example, would have psychological ramifications, although these might not be detectable. I would argue that the psyche must fluctuate in concert with the pathology of cancer. The practical question is this: Is this fluctuation significant enough to detect, and to exploit therapeutically?
References
1. Hinckle LE. The concept of "stress" in the biological and social sciences. Sci Med Man 1973;1:31-48.
2 Cassel J. Psychosocial processes and "stress": theoretical formulation. Int J Health Serv 1974;4:471-82.
3. Lazarus RS, Folkman S. Stress appraisal and coping. New York: Springer Publishing Co., 1984.
4. Williams RB. The role of the brain in physical disease. Folklore, normal science, or paradigm shift? JAMA 1990;263:1971-2.
5. Cohen S, Tyrrell AJ, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med 1991;325:606-12.
6. Kune S. Stressful life events and cancer. Epidemiology 1993;4:395-6.
7. Cunningham AJ. The influence of mind on cancer. Can Psychol 1985;26:13-29.
8. Sklar LS, Anisman H. Stress and coping factors influence tumor growth. Science 1979;205:513-5.
9. Simonton OC, Mathews-Simonton S, Sparks TF. Psychological intervention in the treatment of cancer. Psychosomatics 1980;21:226-33.
10. Newton BW. The use of hypnosis in the treatment of cancer patients. Am J Clin Hyp 1982-83;25:104-13.
11. Meares A. What can the cancer patient expect from intensive meditation? Aust Fam Physician 1980;9:322-5.
12. Morgenstern H, Gellert GA, Walter SD, Ostgeld AM, Siegel BS. The impact of a psychosocial support program on survival with breast cancer: the importance of selection bias in program evaluation. J Chronic Dis 1984;37:273-82.
13. Gellert GA, Maxwell RM, Siegel BS. Survival of breast cancer patients receiving adjunctive psychosocial support therapy: a 10-year follow-up study. J Clin Oncol 1993;11:66-9.
14. Bagenal FS, Easton DF, Harris E, Chilvers CED, McElwain TJ. Survival of patients with breast cancer attending Bristol Cancer Help Centre. Lancet 1990;336:606-10.
15. Chilvers CED, Easton DF, Bagenal FS, Harris E, McElwain TJ. Bristol Cancer Help Centre [letter]. Lancet 1990;336:1186-8.
16. Fawzy FI, Fawzy NW, Hyun CS, et al. Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 1993;50:681-9.
17. Spiegel D, Bloom JR, Kraemer HC, et al. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989;2:888-91.
18. Grossarth-Maticek R, Schmidt P, Vetter H, Arndt S. In: Steptoe A, Mathews A, eds. Health care and human behaviour. New York: Academic Press, 1984:325-41.
19. Fox BH. Quandaries created by unlikely numbers in some of Grossarth-Maticek's studies. Psychol Inquiry 1991;2:242-7. 20. Linn MW, Linn BS, Harris R. Effects of counselling for late stage cancer patients. Cancer 1982;49:1048-55.
21. Ilnyckyj A, Farber J, Cheang MC, et al. A randomized controlled trial of psychotherapeutic intervention in cancer patients. Ann R Coll Physicians Surg Can 1994;27:93-6.
22. Cunningham AJ. From neglect to support to coping: the evolution of psychosocial intervention for cancer patients. In: Cooper C, ed. Stress and breast cancer. New York: John Wiley, 1988:135-54.
23. Ganz PA, Lee JJ, Siau J. Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer 1991;67:3131-5.
24. Weeks J. Quality of life assessment: performance status upstaged? J Clin Oncol 1992;10:1827-9.
25. Cunningham AJ, Tocco EK. A randomized trial of group psychoeducational therapy for cancer patients. Patient Educ Couns 1989;14:101-14.
26. Cassileth BR, Walsh WP, Lusk EJ. Psychosocial correlates of cancer survival: a subsequent report 3 to 8 years after cancer diagnosis. J Clin Oncol 1988;6:1753-9.
27. Von Uexküll T, Pauli HG. The mind-body problem in medicine. Advances, Advancement of Health 1986;3:158-74.
28. Cunningham AJ. Information and health in the many levels of man: towards a more comprehensive therapy of health and disease. Advances, Advancement of Health 1986;3:32-45.
29. Foss L, Rothenberg K. The second medical revolution. Boston: Shambhala, 1987.
30. Fox BH. Current theory of psychogenic effects on cancer incidence and prognosis. J Psychosoc Oncol 1983;1:17-31.
31. Cunningham AJ. Pies, levels and languages: why the contribution of mind to health and disease has been underestimated. Advances 1995. In press.
Author Reference
Alastair J Cunningham, PhD, PhD, CPsych
Senior Scientist, Epidemiology and Statistics
Ontario Cancer Institute / Princess Margaret Hospital
Toronto, Ontario, Canada
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Cortisol, Stress, and Health
Today, we are more stressed than ever before. Men and women are working more hours, teens are committing suicide at high rates, and physicians cannot write enough prescriptions for antidepressant and anti-anxiety medications.
Although modern technology is light years ahead of that of our primitive forebears, our biological make-up has not changed appreciably for many thousands of years. Because of this, understanding how our bodies react to external and internal stressors is vitally important to the quest for optimal health and well-being.
While questions remain as to precisely how stress contributes to the disease process, research has shown that chronic stress causes a significant dysfunction of one of the most vital systems of our body—the neuroendocrine system.1-4
The Mind-Body Connection
The study of brain-body interaction, or psychoneuroimmunology, is one of the most contentious fields in medicine today. While more researchers and physicians believe that the mind and body are one, a significant number of doctors still insist that the mind and body are separate entities that have only minimal interaction.
Of course, this stubbornness is not surprising, as Western medicine has long held as one of its major axioms that the mind and body are separate entities. By contrast, Chinese and other traditional medicines have always recognized the interconnectedness of the body and mind. For those who still doubt this interplay, recent scientific research proves that what happens in the mind can profoundly influence the body.
The Neuroendocrine Connection
Scientists are just now beginning to unravel the ways in which in the mind influences the body, and vice versa. The hypothalamic-pituitary-adrenal (HPA) axis plays a major role in both mind and body health. The intricate connection between the brain and endocrine system broadly influences our health, and many researchers suggest that our stressful, modern lifestyles are overtaxing the HPA axis.
Before we explore how aberrations of the HPA axis can contribute to many chronic disease states, it is important to understand how the HPA axis works. It starts with the hypothalamus, a specialized glandular area of the brain that some consider the “master gland” of the neuroendocrine system. The hypothalamus has many functions, such as controlling the body’s temperature, water balance, thirst, and hunger. It also acts as a controller of the pituitary gland, a small, bean-sized structure that sits just below the hypothalamus. During times of stress, the hypothalamus releases corticotropin-releasing factor, which in turn signals the pituitary gland to release adrenocorticotropic hormone, or ACTH. This hormone then travels through the bloodstream to the adrenals, two small, triangle-shaped glands located on the top of the kidneys. When ACTH reaches the adrenals, it causes them to release a biochemical known as cortisol.
Cortisol: the Stress Hormone
Cortisol is, in many ways, a paradoxical hormone. A certain amount of cortisol is needed to maintain optimal health, but too much or too little can be deadly. Cortisol is involved in multiple bodily functions, including blood pressure regulation, cardiovascular and immunological function, and the metabolism of fats, proteins, and carbohydrates. In stressful situations, the body secretes cortisol at higher-than-normal rates to help break down and use fatty acids and proteins for energy production, which is especially important for optimal brain function. Unlike levels of other hormones such as testosterone and DHEA, cortisol levels generally do not decrease as we get older. In fact, some researchers now believe that many age-related problems may result from a ratio of increased cortisol and lowered DHEA as we age.5-7
Stress, Cortisol, and Illness
Taking their lead from Selye’s original work, scientists have demonstrated that both acute and chronic levels of stress contribute to elevated levels of cortisol.10-12 In addition, high levels of stress are now known to be significantly linked to various illnesses, including upper respiratory infections,13 exacerbation of multiple sclerosis,14 and gastrointestinal disorders such as irritable bowel syndrome.15,16
Since the mid-1990s, scientists have presented provocative evidence linking cancer, stress, and elevated cortisol levels. In a 1996 case-controlled study, scientists examined hormone levels of the hypothalamic-pituitary-adrenal system in women with both early-stage and metastatic breast cancer.17 Both groups had statistically higher levels of cortisol compared to women without breast cancer. Furthermore, those with metastatic breast cancer had higher cortisol levels than women with early-stage breast cancer. The authors noted, “these data provide evidence that breast cancer is associated with a hyperactive adrenal gland.17
A more recent report in the journal Lancet Oncology summarized what is currently known about the complex interactions between the HPA system, stress, and cancer. According to the authors, “Evidence mainly from animal models and human studies suggests that stress and depression result in an impairment of the immune system and might promote the initiation and progression of some types of cancer…Through HPA activation, the mediators released during chronic stress suppress some non-specific and specific parts of the immune response…compromising the most important effectors of the immune response against tumors.”18
While cancer is probably the most widely feared chronic disease, heart disease remains the number-one killer of Americans. Mayo Clinic researchers examined the medical and economic costs of stress in heart disease patients.19 In a study of 311 men and 70 women, the authors found that patients with the highest stress levels had markedly higher rates of rehospitalization and reoccurrence of further heart disease-related problems, including heart attacks and cardiac arrest. Concluding that psychological distress may adversely affect prognosis in heart disease patients, the authors suggested that identifying and treating psychological distress could improve outcomes in these patients.
A more recent report in the European Heart Journal supports the theory that stress can literally be a killer.20 In this 21-year prospective study of nearly 14,000 men and women, researchers concluded, “chronic stress is an independent risk factor for [cardiovascular disease], particularly fatal stroke.” Other scientists, however, have criticized these data, indicating the need for further investigation.
Alzheimer’s disease, the most common cause of dementia in those aged 65 or older, is characterized by a progressive decline in cognition and memory. This debilitating condition currently affects over 15 million people worldwide. With the rapidly aging US population—an estimated 30% of all Americans will be 65 or older by the year 2050—projections are that 14 million people in the US alone will be affected by Alzheimer’s in the next few decades.21,22 This represents a quadrupling over the current prevalence of Alzheimer’s in the US.
Although scientists continue to search for the root cause of this devastating illness, new evidence suggests that increased levels of stress, along with high levels of cortisol, may play a significant role. Research indicates that high cortisol levels may promote degeneration and death of neurons,23-25 along with decreased memory function in otherwise healthy elderly men and women.26 Furthermore, a recent report in the journal Neurology showed that chronic stress is associated with the risk of developing Alzheimer’s disease.27 In this study, researchers found that people who were prone to experiencing high levels of stress had twice the risk of developing Alzheimer’s as those who were not prone to stress. The authors concluded, “proneness to experience psychological stress is a risk factor for [Alzheimer’s disease].”
While mainstream medicine offers little in the way of reducing chronic stress or high cortisol levels, making behavioral changes and using certain supplements can help you bring your stress load and high cortisol levels safely under control.
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9. Selye H. The general adaptation syndrome and the diseases of adaptation. J Clin Endo. 1946;6:117-20.
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