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Duke Physician Discusses Gene-Environment Matrix in Stress Response

By Eddy Ball
September 2007

Williams concluded his lecture with an impassioned call for action.
Williams concluded his lecture with an impassioned call for action. "We've got to do this research," he told the audience. (Photo courtesy of Steve McCaw)

David A. Schwartz, M.D., asked the speaker to respond to social, ethical and legal implications of choosing the people best suited to be caregivers based on genotype. (Photo courtesy of Steve McCaw)
David A. Schwartz, M.D., asked the speaker to respond to social, ethical and legal implications of choosing the people best suited to be caregivers based on genotype. (Photo courtesy of Steve McCaw)

Director of the Office of Risk Assessment Chris Portier, Ph.D., wanted more details about the studies of polymorphisms in the gene encoding serotonin transport. (Photo courtesy of Steve McCaw)
Director of the Office of Risk Assessment Chris Portier, Ph.D., wanted more details about the studies of polymorphisms in the gene encoding serotonin transport. (Photo courtesy of Steve McCaw)

The audience included a number of employees in the Division of Extramural Research and Training. Shown here are David Balshaw, Ph.D., left, and Beth Anderson. (Photo courtesy of Steve McCaw)
The audience included a number of employees in the Division of Extramural Research and Training. Shown here are David Balshaw, Ph.D., left, and Beth Anderson. (Photo courtesy of Steve McCaw)

NIEHS welcomed Duke University Professor Redford Williams, M.D., to its Frontiers of Environmental Sciences Lecture Series on August 10 in Rodbell Auditorium. Redford, who is the director of the Behavioral Medicine Research Center at Duke, spoke on "Stressful Social Environments and Genes: Effects on Mental and Physical Well-Being." His talk was hosted by Liam O'Fallon, a program analyst in the Division of Extramural Research and Training.

A well-known authority on the interplay of genes, the social and physical environment, behavior and pathology who has written over 100 peer-reviewed studies, Williams served as a participant in an NIEHS-led trans-NIH program on health disparities. He has also received several other grants from NIH to pursue his research interests.

Williams opened his talk with an overview of the current disease-focused medical practice model and the changes in philosophy that need to be made in order to improve health care in the United States, which currently costs payers an estimated $1.5 trillion each year. Most of that amount is spent on what Williams called "the usual suspects" in a belated attempt to "find and fix" chronic diseases long after they have developed.

Among the psychological and social risk factors Williams has studied are hostility and anger, depression, childhood adversity, social isolation and low socioeconomic status. "These factors tend to cluster in the same individuals and groups, especially in people of low socioeconomic status," he explained, "and when the psycho-social factors cluster, they have an enhanced effect."

According to Williams, these factors can interact with particular genes to affect emotional, behavioral and physical health. In combination, genetic and environmental factors have a disproportionately greater effect on outcomes than they do individually. These interactions, some of them gender- or race-specific, can mean that individuals with different polymorphisms may react much differently to the same environmental stresses.

The combination of genotype and environmental stress can determine whether subjects develop emotional problems that in turn may accompany or trigger disease risk and pathology. Williams presented study results based on outcomes such as high blood pressure, elevated glucose, high C-reactive protein levels, major depression, anti-social behavior and recurrent cardiovascular events following myocardial infarction as a function of genotype and life experience.

Using a study on depression as an example, Williams explained, "If you don't have the wrong genotype, stressful life events don't affect your risk of depression. If you don't have stressful life events, genotype doesn't affect your risk of depression."

Williams then turned to the translational aspects of his research, reviewing some of the promising research into the benefits of incorporating behavioral therapy with other treatment. He referred to studies of post-myocardial infarction patients who showed significant improvements in recurrent cardiovascular event rates and hospitalization rates after receiving behavioral and cognitive therapy interventions to reduce type A behavior, manage stress or control hostility along with usual care.

Results of a study of incorporating structured coping-skills training into treatment of patients with chronic disease in Hawaii showed a 20% decline in the costs of primary care, a decrease in systolic blood pressure (SBP) reactivity and increases in emotional health indicators. Primary care costs for patients who did not receive the training increased by 20%, and a group receiving individualized psychotherapy fared even worse. These control groups also showed worse outcomes in terms of SBP and emotional health indicators.

In contrast to the disease-oriented practice of medicine, Williams concluded, "we need to have a prospective evaluation that involves a health profile summary, health risk analysis, including genetic and lifestyle factors, and a five-year plan [of preventive interventions]. We can, instead of spending most of our healthcare dollars after disease has developed, spend them on prevention."


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