If you've ever wondered why it seems that you are more likely to catch a cold when you're racing the clock against a pressing work deadline or when your calendar is so booked that you can't find a moment to pick up the dry cleaning, there is likely a good scientific reason.
A growing body of evidence indicates that prolonged psychological stress can take a very real toll on physical health, causing increased susceptibility to infection, a weakened immune response to vaccines and even slowed wound healing.
Exploring the interaction between mental health and immune-system function ?particularly as it relates to cancer-is the research focus of Dr. Bonnie McGregor, a clinical psychologist who joined the Public Health Sciences Division last fall.
"Breast-cancer patients can be under a considerable amount of stress related to their therapy, such as that due to nausea and fatigue, body-image changes and concerns about relationships and health insurance," she said. "How a patient copes with these stressors can influence their health.
"Although acute stress may actually improve immune function, chronic stress is known to suppress immune function, and this may have a negative effect on the patient's overall health."
By examining the connection between chronic stress and immune-system function among women at risk for breast cancer, McGregor's work ultimately could lead to psychological intervention strategies that help to improve cancer patients' quality of life and their physical health abilities.
Cytokine communication
The brain and the immune system communicate constantly through chemical messengers in the form of hormones and proteins known as cytokines, which trigger a variety of immune responses. Cytokines and the receptors through which they act are produced by cells of both the immune- and central-nervous systems and provide a critical link between the two.
The hormonal link between the brain and the immune system is mediated by the hypothalamus, a region of the brain involved in regulating bodily temperature, certain metabolic processes and other involuntary activities. During periods of chronic stress, the hypothalamus reacts by initiating a cascade of hormonal events that culminate in the release of cortisol by the adrenal cortex, a tiny gland that sits on top of the kidneys. Cortisol not only prepares the body to face a stressful situation, but also suppresses the immune system by decreasing the number and function of immune cells circulating in the bloodstream.
McGregor's interest in this complex mind-body connection was formed by her firsthand observations of many stressors encountered by cancer patients. While working as a research technician in the Transplant Biology program from 1987-1995, before she embarked on her career in clinical psychology, McGregor served as a volunteer to support Fred Hutchinson bone-marrow transplant patients and their families.
"I was working in the lab with patients' white blood cells, studying how their immune systems were working, but I was also working with the patients themselves, and I learned that a bone-marrow transplant is a very stressful procedure."
Around that same time, McGregor came upon some scientific literature that described the relationship between psychological health and immune functioning. The convergence of events set off a spark that prompted a career change.
"I realized what I really wanted to do was to help find ways to improve immune function and physical health by improving mental health," she said.
McGregor was accepted into the clinical health psychology program at the University of Miami, one of the leading behavioral-medicine research programs in the world. She became involved in a research project funded by the National Cancer Institute to study how cognitive behavioral stress-management intervention could help patients with early stage breast cancer. McGregor led the support groups designed to help patients cope with stress and evaluated the effects on immune functioning.
One important finding to emerge from the research was that patients who participated in the study reported having found benefits to going through the experience of having cancer.
"For example, a patient would say that before cancer, a flat tire would really ruin her day," McGregor said. "Yet after her diagnosis and treatment, she considered a flat tire nothing compared to having a port installed or losing all of her hair."
What's more, this type of emotional growth was also associated with improvements in a simple test of immune function that measures responsiveness of disease-fighting cells known as T lymphocytes.
McGregor describes the emotional system as a muscle: The more it is flexed and used, the stronger it becomes.
"Cognitive behavioral-stress management makes patients stronger, helping them cope better with future stressors," she said. "Our theory is that better coping leads to less stress and better immune function. A lot of time is spent figuring out what makes people sick. It is also important to look at what makes people strong and resilient."
McGregor is well aware of the controversy surrounding studies of the effect of psychological intervention on long-term survival of metastatic breast-cancer patients. Although some of these studies reported a clear benefit on the long-term survival of patients, other studies were unable to replicate this result.
"Many new areas in science are controversial, but with time, good science prevails," she said.
"When you think about it, chemotherapies do not cure all cancers. It is probably true that psychological interventions, while potent in many ways, are not strong enough to stop something as aggressive as metastatic breast cancer. However, psychological interventions can decrease distress, improve coping and quality of life and improve adherence to treatment, which could impact survival."
'Good science'
McGregor plans to be an active contributor to that "good science." Her next step will be to evaluate the effectiveness of psychological interventions in reducing stress and improving immune function among women at elevated risk for breast cancer. In collaboration with Dr. Nancy Haigwood, an immunologist and vaccine expert at the Seattle Biomedical Research Institute and the University of Washington, and Dr. Olivera Finn, a breast cancer tumor-vaccine expert at the University of Pittsburgh, McGregor will use robust methods to compare antibody response to vaccination in women who receive a psychological intervention to those who do not. If such interventions improve women's immune response, the approach could be tested in breast-cancer patients who are undergoing therapy with vaccines to treat their disease.
McGregor also will collaborate with colleagues at the center who are experts in intervention studies and work with women at risk for breast cancer.
"The excellent research environment at Fred Hutchinson will allow me to do good science," she said. "This will contribute to a better understanding of the relationship between stress, immune functioning and health."
[Dr. Annemieke DeMaggio is a postdoc in the Human Biology Division.]
