Killer Stress


Scientific Research Linking Disease to Life’s Stresses

Anyone who’s ever drowned their sorrows in a pint of ice cream—perhaps secretly consumed at midnight in the wake of a lost job or broken heart—knows about “stress eating.” It’s the stuff of legend and gossip, but until recently, science has scoffed at the notion that stress leads to obesity or other kinds of diseases.

“Despite widespread public belief that psychological stress leads to disease, the biomedical community remains skeptical of this conclusion,” said Dr. Sheldon Cohen, a professor of psychology at Carnegie Mellon University in Pittsburgh.

But when Cohen and colleagues from the University of British Columbia in Canada reviewed the relevant research, they found serious scientific support for our everyday beliefs.

In the Oct. 10 issue of the Journal of the American Medical Association, the group was able to show a cause-and-effect connection between stress and disease, offering modest results from short-term clinical trials and stronger evidence from medical studies that tracked large groups of people over time. They also uncovered solid information about stress and disease in “natural experiments” such as natural disasters.

The belief that stress can steal valuable parts of your life was clearest in two of the cases that Cohen reviewed: depression and cardiovascular disease. Stress also emerged as a “probable cause” culprit in the progression of HIV to AIDS.

However, when the researchers examined cancer’s relationship to stress, the prosecution didn’t pan out. They were unable to find convincing data on psychological stress as a risk for cancer onset, progression or recurrence, although they did say that better detective work might uncover stress and cancer connections in the future.

Separately in Washington, Georgetown University researcher Dr. Zofia Zukowska has made groundbreaking discoveries that convincingly lay out the chemical and cellular pathways between physical and social stresses and the onset of disease. Although much of her work is with mice, the hormones and pathways involved are identical to or closely resemble those in the human body.

Zukowska is chair of the Department of Physiology and Biophysics at Georgetown’s School of Medicine and a founding director of a new medical center there devoted to the study of stress and disease. On Sept. 25, she gave a presentation titled “Stress and Obesity – It’s Not Just in Your Mind” as part of the university’s fall “Mini-Medical School” lecture program.

What all of these experts have concluded is that, yes, stress can kill you—or at least pummel your mind and body in ways that weaken them and make disease-promoting conditions more likely.

But what exactly is “stress”? At her recent Georgetown presentation, Zukowska defined it as a mentally or emotionally disruptive condition that results from adverse circumstances. These circumstances could be external hardships, internal mental pressures or extreme life difficulties. Cohen and his colleagues define it as environmental demands that “tax or exceed” an individual’s coping skills.

Not all stress, however, is bad. If people rise to a challenge and adapt, that’s good, Zukowska said, although she added that even when people cope well, there’s still a certain amount of “wear and tear” caused by responding to stress. Cohen and his colleagues reported that repeated, sustained stress can throw off many body systems, from metabolism to resting heart rate to the body’s response to infection.

In particular, research has clearly linked clinical depression to stress stemming from major life blows, according to the Cohen group. In one study, 50 percent to 80 percent of the depressed persons studied had experienced a major negative life event during the three months to six months preceding the onset of their depression. During that same period, only 20 percent to 30 percent of the non-depressed people in the group had similar experiences.

Stress also affects how deep a depression is and how long it lasts. Even with antidepressant medications and counseling, depressed patients who experienced ongoing stress tended to have recovery problems, studies found, and were more likely to relapse than those whose troubles were largely behind them.

On another front, animal research is providing “strong support” for stress as a contributor to heart disease, Cohen’s group said, with similar support coming from studies of both healthy humans and people with poor cardiovascular health. Long-term studies that track groups of initially healthy humans have also discovered considerable links between psychological stress and deaths from heart attacks.

One study, for example, came up with a whopping 50 percent increase in heart attacks among people with certain kinds of job-related stress—particularly individuals who had little control over a workplace that was hitting them with high demands, low pay or unjust circumstances. Traumatic events such as childhood abuse or combat in war can also make heart disease more likely later on in life, researchers found—as can an unhealthy marriage or social isolation.

Moreover, the Cohen group found that research published since 2000 generally supports a link between stress and HIV progression. People infected with HIV, the virus that causes AIDS, vary considerably as to how well they respond to medications and how fast they develop full-blown AIDS. In some, the progression to serious illness is rapid, with related diseases developing quickly, while in others the progression can be quite slow. Studies have found that social stressors, including stigma and lack of acceptance, can have a negative effect and hasten health deterioration in HIV-infected people. Animal studies also link stress to worsened HIV and AIDS outcomes.

Cancer is not one disease but many, and the complexities of long-term onset and treatments make teasing out the role of stress more difficult than with other diseases. Researchers have not yet reached any clear conclusions one way or another, Cohen’s group said, but the concept is still being explored, as is the role of stress in a number of other diseases and conditions. These include the common cold and asthma, herpes infections, autoimmune diseases such as multiple sclerosis, and wound healing.

But one of the most closely watched scientific research areas examining the connection between stress and disease, not surprisingly, deals with obesity. “Metabolic syndrome” is a combination of medical problems that can put people at risk for diabetes, stroke and heart disease. Symptoms include high blood pressure, high levels of “bad” cholesterol, faint signs of diabetes, and mysteriously higher levels of inflammation and white blood cells in the body.

One key contributor to this syndrome is belly fat. Doctors now know that fat around your middle—a pot belly sometimes called a “beer belly” in men or a thick waist and protruding tummy in women—puts you at risk for developing metabolic syndrome and its accompanying diseases.

At Georgetown University, Zukowska has convincingly tied belly fat to stress, recently demonstrating exactly how stress triggers the accumulation of this dangerous type of fat.

In general, studies that link stress to disease invoke two stress systems in the body: the “fight or flight” response to stress, as well as the nervous system and hormones such as cortisol. The hormone that triggers belly obesity, Zukowska has shown, is a neuropeptide called “Y” (NPY), which serves as a chemical messenger between cells. We generally think of neuron messengers as brain chemicals, but in fact they are widely distributed throughout the body. And neuropeptide Y, the most abundant peptide in the brain and heart, affects fat.

According to Zukowska, the predominant thinking is that fat is inert, “but it’s not. It has blood cells. It can get inflamed,” she said, explaining that NPY can thicken blood vessels, cause more blood to flow into tissues, and create fat deposits. It also makes new fat cells, fills up old ones, and forces fat stores to expand.

Just as important, NPY is part of a system that tells the body to make a specific kind of fat—belly fat—and stress triggers NPY.

Zukowska’s research has uncovered high levels of NPY in mice subjected to chronic stress in the form of “cold feet” (which they dislike) or in the form of having to put up with a quarrelsome mouse put into their cages. Even if they periodically have to live with a bully mouse for a brief 10-minute time frame, their NPY hormone levels shoot dramatically up.

If these stressed mice are fed a regular diet, they’ll gain some weight. But if they’re fed a high-fat diet, they’ll gain a lot of weight, quickly becoming obese—and this new fat converges around the belly. Zukowska’s research found that being stressed out doubles the weight-gain effect of a high-fat diet because stress pumps NPY into fat cells and causes them to multiply and expand. Zukowska noted that the NPY in mice is chemically the same as the NPY in humans, and the mechanism in humans is similar.

But why is belly fat such a culprit? Zukowska and other researchers aren’t sure, but they suspect that evolution could provide some answers. Belly fat might have been adaptive in early humans at a time when stressors were likely to have included finding enough food to survive. Zukowska pointed out that hibernating bears store the fat they survive on through the winter around their bellies, where such fat is kept close to the digestive system.

But Zukowska cautioned that the relationship among stress, diet and fat is not automatic. Some people lose weight when stressed, while others gain it. Your individual genetic makeup, family history, lifestyle and ability to cope with stress all play a part. However, food intake and energy expenditure matter, and the take-home message is that the combination of a high-stress lifestyle and a high-fat diet could be extremely detrimental to your health.

There’s an “obesity epidemic not only in the United States, but globally,” Zukowska observed, with one statistic for the number of Americans with metabolic syndrome set at 47 million. While waiting for a medical “magic bullet” that will interfere with the NPY fat-making mechanism or modify other components of the stress system that lead to disease, your best bet, she recommended, is to control your diet, exercise as much as you can, improve your coping skills and work to lower the stress that has become an all-too familiar aspect of everyday life.

Likewise, the online WebMD and Prevention magazine offer advice for fixing belly fat, listing five research-based nutritional tactics to tackle abdominal obesity: eating fruits and vegetables, especially orange ones; taking a selenium supplement to ensure 55 mcg a day; making sure you get 25 percent of your calories from protein; drinking a four-ounce glass of red wine a day (up to 20 a month); and eating the right fats, including olive oil and the fats found in fish, walnuts and flaxseed.

About the Author

Carolyn Cosmos is a contributing writer for The Washington Diplomat.