Physicians and lay people alike have observed the power of a positive mental attitude in successfully recovering from an illness. As a resident at UCSF in the mid-1990s, Mary Whooley made the same observation and a more disturbing one. "I noticed that many of my patients were depressed and that feeling depressed seemed to affect their physical health as well," says Whooley, now a staff physician and researcher at the San Francisco VA Medical Center (SFVAMC).

Rather than just make note of these trends, Whooley, a graduate of Yale and Boston University Medical School, chose to focus her career on improving the treatment of depression in the primary care setting and on understanding the effect of depression on health outcomes. "My main goals are to enhance detection and treatment in patients with depression and to help improve the quality of life of patients in general."

At the time of her training, the treatment of depression in a primary care setting was not as commonplace as it is today. So, in 1997, she and her colleagues came up with a two-question screening tool for depression that has since become widely used by primary care physicians across the country. She then coauthored a study that showed patients with many symptoms of depression were more likely to die over a seven-year follow-up period.

That work has led to the ambitious project that Whooley now heads. She is the principal investigator of the "Heart and Soul" Study, a three-year analysis of more than 1,000 patients with heart disease. Its goal: to explain the connection between depression and cardiac outcomes. The participants in the study have a mean age of 67 and were recruited from the SFVAMC, the Palo Alto VA Medical Center, UCSF Medical Center and nine public health clinics in the Community Health Network of San Francisco.

Consequences of depression

Whooley and her colleagues began by establishing baseline data for the degree of cardiac disease through EKG, treadmill and other detailed medical tests. They also tested patients for depression and other psychiatric conditions. For three years, the patients will be contacted annually for new physical and psychiatric evaluations.

Whooley's theory is that depression doesn't just affect a person's health by dampening a person's motivation to take care of oneself, but actually exacerbates his or her illness. "I think depression has biological and physiological consequences," she explains.

One way this may happen, Whooley says, is through depression's effect on heart rate. The heart of a healthy patient responds to normal variation in activity -- resting versus climbing a set of stairs, for example -- by increasing or decreasing the rate at which it beats. According to Whooley, unhealthy patients have a high heart rate all the time. This low variability in heart rate is associated with increased mortality. It also turns out, she says, that low variability in heart rate -- a constantly rapidly beating heart -- is linked with depression. Whooley hopes the Heart and Soul Study will reveal whether or not low heart rate variability accounts for the increased mortality seen in depressed patients.

Whooley says she has both her scientist's intuition and her perspective as a woman to thank for her interest in the mind-body connection. "Some people say that women tend to be more in touch with their emotions. Perhaps this led to a greater appreciation for the effect of emotions on my patients' physical health."

The way she goes about her day-to-day work is also affected by the reality of being a working mother of three children all under the age of 6 years. "Having a family helps me set priorities and keeps me efficient and effective with the time that I have to work," says the San Francisco native. Balancing work and family is not always easy, Whooley concedes, but she has felt nothing but support from UCSF administrators and its scientific community as a whole. Whooley admits, however, that women in science work in a less-than-equitable environment. "Society as a whole has not achieved an acceptable level of gender equity," she says. But she credits the progressive attitude of the collective leadership at UCSF with creating an environment where she can thrive. "I can focus on doing the science."