When the Body Says No: The Cost of Hidden Stress (15 page)

The messenger molecules and most of the hormones are made of amino acids, the basic building blocks of protein. They are called peptides, the technical name for longer chains of amino acids. None of these chemicals are restricted to any one area or organ of the body. An eminent neuroscientist has suggested the term “information substances” to describe the entire group, because they each carry information from one cell or one organ to another. There are multiple potential interactions between information substances emanating from each part of the PNI system and cell types in each other part.

The hub of the PNI system is the hypothalamic-pituitary-adrenal nexus: the HPA axis. It is through the activation of the HPA axis that both psychological and physical stimuli set in motion the body’s responses to threat. Psychological stimuli are first evaluated in the emotional centres known as the limbic system, which includes parts of the cerebral cortex and also deeper brain structures. If the brain interprets the incoming information as threatening, the hypothalamus will induce the pituitary to secrete an adrenocorticotropic hormone. ACTH, in turn, causes the cortex of the adrenal gland to secrete cortisol into the circulation.

Simultaneously with this hormonal cascade, the hypothalamus sends messages via the sympathetic nervous system—the flight-or-fight part of the nervous system—to another part of the adrenal, the medulla. The adrenal medulla manufactures and secretes the flight-fight hormone, adrenalin, which immediately stimulates the cardiovascular and nervous systems.

The same influences that the organism is most likely to interpret as emotionally stressful are, not surprisingly, also the most powerful
psychic triggers for the HPA axis: “Psychological factors such as
uncertainty, conflict, lack of control, and lack of information
are considered the most stressful stimuli and strongly activate the HPA axis. Sense of control and consummatory behaviour result in immediate suppression of HPA activity.”
⁶

Consummatory behaviour—from the Latin
consummare
, “to complete”—is behaviour that removes the danger or relieves the tension caused by it. We recall that stress-inducing stimuli are not always objective external threats like predators or potential physical disasters but also include internal perceptions that something we consider essential is lacking. This is why lack of control, lack of information—and, as we will see, unsatisfied emotional needs (e.g., lack of love), trigger the HPA axis. Consummation of such needs abolishes the stress response.

Given the biochemical and neurological cross-influences within the PNI system, we can readily understand how emotions are able to interact with hormones, immune defences and the nervous system. In cancer causation, disturbed hormonal activity and impaired immune defences both play a role. Lung cancer is a prime example.

The mechanistic view holds that cancer results from damage to the DNA of a cell by some noxious substance—for example, tobacco-breakdown products. This perspective is valid as far it goes but cannot explain why some smokers develop cancers while others do not, even if the amount and type of tobacco they inhale are exactly the same. The unanswered questions are, Why are the cells of some individuals more susceptible than those of others? Why does DNA repair occur in some people but not in others? Why do the immune system and other defences keep cancer at bay in some people but not in others? What accounts for vast differences in cure or disease progression from one person to the next, even when the identical cancer is diagnosed at exactly the same stage and even when all other factors—age, gender, income, general health—are exactly matched?

Genetic variations may explain these issues in some cancers, although, as we have seen with breast cancer, in the majority of people heredity does not play a role in cancer causation. Lung cancer, specifically, is not a genetically transmitted disease, nor is the damage to genes in lung cancer due to heredity.

The development of any malignancy progresses through several
stages, the first of which is
initiation
, the process by which a normal cell becomes transformed into an abnormal one. Cancer may be seen as a disease of cell replication. The normal processes of cell division and cell death are somehow subverted. A cell that should give rise to healthy offspring escapes from control and divides into malformed facsimiles that replicate themselves without regard to the biological needs of the organism. With millions of cells dying or being formed in the body every day, natural accident would, by itself, lead to a great number of spontaneous abnormal transformations. “It’s a fact that every one of us has a number of tiny cancerous tumours growing in our bodies at every moment,” writes Candace Pert.

Tobacco smoke has a directly damaging effect on the genetic material of lung cells. It has been estimated that for the initiation of cancer, lung cells have to acquire as many as ten separate lesions or points of damage on their DNA. Yet, no matter where in the body, such genomic damage “seldom leads to tumour formation. This is principally due to the fact that most primary lesions are transient and are readily eliminated by DNA repair or cell death.”
⁷
In other words, DNA repairs itself or the cell dies without replicating its damaged genetic material—which, no doubt, accounts for the fact that most smokers do not develop clinical lung cancer. Where cancer does arise, either DNA repair or the normal process of cell death must have failed. In a 1999 review of psychological effects on lung cancer, researchers from the Ohio State University College of Medicine wrote: “Faulty DNA repair is associated with an increased incidence of cancer. Stress may alter these DNA repair mechanisms; for example, in one study, lymphocytes from psychiatric inpatients with higher depressive symptoms demonstrated impairment in their ability to repair cellular DNA damaged by exposure to X-irradiation [X-rays].”
⁸
Impaired DNA repair has also been documented in studies of stressed laboratory animals.

Apoptosis
is the scientific term for the physiologically regulated death necessary for the maintenance of healthy tissues. Apoptosis ensures normal tissue turnover, culling older cells with weakened genetic material, leaving room for their healthy and vigorous offspring. “Dysregulated apoptosis contributes to many pathologies, including tumour production, autoimmune and immunodeficiency diseases, and neurodegenerative disorders.”
⁹

Steroid hormones released through the activity of the HPA axis help regulate apoptosis in a number of ways. Habitual repression of emotion leaves a person in a situation of chronic stress, and chronic stress creates an unnatural biochemical milieu in the body. Perpetually abnormal steroid hormone levels can interfere with normal programmed cell death. Also participating in cell death are natural killer cells. Depression—a mental state in which repression of anger dominates emotional functioning—interacts with cigarette smoking to lower the activity of NK cells.
¹⁰

In short, for cancer causation it is not enough that DNA damage occur: also necessary are failure of DNA repair and/or an impairment of regulated cell death. Stress and the repression of emotion can negatively affect both of those processes. The findings of the Cvrenka investigators and of the British surgeon David Kissen make physiological sense when we consider the first stage of malignant transformation, that of initiation.

A two-part article published in the
Canadian Medical Association Journal
in 1996 reviewed the role of the PNI system in health and disease. “In healthy people,” noted the authors, “neuroimmune mechanisms provide host defence against infection, injury, cancer, and control immune and inflammatory reactions, which pre-empt disease.”
¹¹
Disease, in other words, is not a simple result of some external attack but develops in a vulnerable host in whom the internal environment has become disordered.

Subsequent phases of cancerous change are
promotion
and
progression
. Having escaped the normal regulatory mechanisms that should have prevented their survival, the newly malignant cells continue to divide, leading to the formation of a tumour. At this stage, tumour growth can be inhibited or supported by the body’s internal environment. The PNI super-system comes into play. Acting chiefly through hormonal regulation by the HPA axis, it creates a milieu in the body tissues that is either receptive or hostile to the growth and spread of cancer.

“The chronic psychological status of the individual may play an important role either in facilitating tumour promotion or in dampening or accentuating the impacts of environmental stress,” Dr. Marc E. Lippman, head of the breast cancer section, Medicine Branch, National Cancer Institute, Bethesda, Maryland, has written. “The human endocrine system provides one critical mediator of interaction between
psyche and tumor…. It seems inescapable that psychic factors which can evoke endocrine changes will have effects on actual tumour biology.”
¹²

The effect of hormones on the growth and spread of cancer is twofold. First, many tumours are directly hormone dependent, or they arise in organs intimately involved in hormonal interactions, such as the ovaries or the testes. Hormone-dependent cancer cells bear on their membranes receptors for various hormones capable of promoting cell growth. One example of a hormone-dependent cancer is that of the breast. It is generally understood that many breast cancers are estrogen dependent, this being the rationale for the use of the estrogen-blocking drug tamoxifen. Less well known is that some breast cancers have receptors for a broad array of other “information substances,” including androgens (male sex hormones), progestins, prolactin, insulin, vitamin D and several more—all of them secreted by the HPA axis or regulated by it.

Stress is a powerful modulator of hormonal function, as seen in both human experience and animal studies. In one experiment, researchers manipulated the dominance relationships in groups of female monkeys. Established dominance patterns were broken up. Some previously dominant animals were forced into subordination, while subordinate ones were enabled to achieve dominant status.

Social subordination caused hormonal dysfunctions of the HPA axis and of the ovaries. “Females that were currently dominant secreted less cortisol than those who were currently subordinate.” Dominant female monkeys had normal menstruations and higher concentrations of progesterone prior to ovulation. Subordinates ovulated less often and more frequently had impaired menstrual cycles.

When the experimental situation was altered so that previously dominant monkeys became subordinate, their reproductive function was almost immediately suppressed and their cortisol production went up. The reverse was the case in monkeys previously subordinate but newly made dominant.
¹³

Cancers of the female gynecological organs such as the ovaries and the uterus are also hormone related. Ovarian malignancy is only the seventh most common cancer in women, but it is the fourth leading cause of cancer deaths. Of all cancers, it carries the highest tumour-to-death ratio: that is, it has the poorest prognosis. In 1999, twenty-six hundred Canadian women were diagnosed with ovarian cancer. In the
same year, fifteen hundred died of it. In the U.S. about twenty thousand women are diagnosed annually; nearly two-thirds of them will succumb to the disease. Although early treatment is highly effective, by the time most cases are diagnosed, the cancer has advanced beyond the ability of current treatment to cure it.

As yet there are no effective screening tests to identify the initial stages of this disease. Ultrasounds and a blood test, called CA-125, are useful in monitoring treatment, but neither is reliable as a tool to find the cancer before it causes symptoms or before it spreads beyond its site of origin. Darlene, an insurance broker, was diagnosed during the course of an infertility workup. “They did a laparoscopy to look at my ovaries,” she says, “and that’s how they found the cancer. So instead of a child, I ended up with an oophorectomy.”

Since infertility is one of the known risk indicators for ovarian cancer, hormonal factors are obviously important. Unfortunately, the picture is confusing. Early menses and late menopause increase the risk of developing ovarian cancer, while pregnancies and the birth control pill decrease it. This pattern would suggest that the more women ovulate, the more susceptible they become to the disease. On the other hand, infertility—when no ovulation takes place—also adds to the risk. Evidently the hormonal influences here are subtle and complicated. What we do know about the hormones of female reproduction is that they are exquisitively sensitive to women’s psychological states and to the stresses in their lives. Hormonal function may also be related to certain character traits, as a study at the University of Pittsburgh in 2001 concluded.

Researchers at the Pittsburgh School of Medicine compared the psychological characterisitics of women with chronically missed periods—amenorrhea—with women whose menstruation was normal. They were particularly interested in a group with functional hypothalamic amenorrhea (FHA), that is, the group of women who had no identifiable disease or condition to account for the lack of normal ovulation. The study found that “the women with FHA reported more dysfunctional attitudes, particularly those associated with need for approval. [They] were more likely … to endorse attitudes that are prevalent among persons vulnerable to depression, such as perfectionistic standards and concern about the judgment of others.
¹⁴

A major finding of the Pittsburgh researchers was the discovery of subtly but significantly disturbed eating habits in non-menstruating women. Troubled eating patterns are inextricably linked with unresolved childhood issues, as we will see, for example, in the case of the comedienne Gilda Radner who died of ovarian cancer. The stresses that create the problems with self-nurture are also stresses that predispose to ill health. The authors of the Pittsburgh study write that “women with FHA report more concerns about dieting and weight, fear of weight gain, and tendencies to engage in binge eating.”