Stress Found to Weaken Resistance to Illness

By Shankar Vedantam
Washington Post Staff Writer
Monday, December 22, 2003

Scientists are gaining new insights into the role of temperament in making some people vulnerable to physical disease through studies exploring how stress influences the immune system, weakening disease-fighting cells and creating fertile environments for pathogens.

This month, a carefully done study showed that shy men have much less resistance to the AIDS virus than extroverted men and benefit far less from treatment with antiretroviral drugs. It is the first study to demonstrate through laboratory tests a connection between being introverted and the course of AIDS in individuals, researchers said.

Such studies are sketching in the details behind the growing awareness that the workings of the body and mind cannot be neatly compartmentalized into the departments and disciplines taught in medical school. As a result, paying attention to the emotional state of patients with infectious and chronic diseases is increasingly more than a matter of good bedside manner; it is becoming an essential part of treatment.

Although the connection between emotion and disease has long been suspected -- physicians as early as the 2nd century A.D. observed a link between "melancholy" and physical illness -- researchers are finally pinpointing networks of biological systems that connect temperament with the progression of illness. Cascades of complex chemical signals flow through pathways from the brain to the body and back, often triggering "fight or flight" responses in the short term but decreasing resistance to illness in the long run. Some signals speed up heart rate; others burn muscle and bone. Some changes make cells more vulnerable to viruses.

The consequences can be dramatic. In the new study, HIV-infected men who were introverted, reserved and kept to themselves had nearly eight times as many viral particles in their blood compared with outgoing men. After treatment with antiretroviral drugs for as many as 18 months, the viral load among extroverted men fell 162 fold. Among shy men, the drop was only 20 fold, said lead author Steve Cole at the AIDS Institute of the University of California at Los Angeles.

"There is a link between psychological profile and poorer response to HIV, and maybe even a number of other viral diseases," agreed Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the federal government's lead research center in the fight against AIDS.

Other research has shown similar connections between mental disorders such as depression and AIDS, osteoporosis, even cancer. A study of 5,000 people with depression showed they had twice the risk of developing cancer compared with people without the mental disorder, said David Spiegel, a professor of psychiatry at Stanford University School of Medicine. And Philip Gold, chief of the clinical neuroendocrinology branch at the National Institute of Mental Health, found that pre-menopausal women who were depressed had a higher rate of bone loss and a two- to three-fold higher risk of osteoporosis compared with other women.

The UCLA study, published in the journal Biological Psychiatry, has offered important clues into the physiological pathways through which stress influences the body, which could soon suggest targets for treatment to combat its effects.

"People who have the shy, sensitive temperament seem to be more prone to having sympathetic nervous system responses," Cole said in an interview, referring to the part of the nervous system that causes accelerated heart rate and other unconscious changes. "They are more stressed by lots of things, including contact with unfamiliar people."

In shy people, the nervous systems may be more likely to produce a stress reaction during social interactions -- so they maintain their internal stress balance by limiting contact with other people.

Previous work had shown that AIDS progresses more rapidly in gay men who were in the closet, compared with those who were "out." Initially, Cole said, scientists speculated that the hiding and secrecy raised the stress level and made them vulnerable. But increasingly, he said, scientists think of being in the closet as a marker -- rather than a cause -- of poor outcomes. Because shy people are more sensitive to humiliation, rejection and the opinions of others, shyness could be the reason some gay men with HIV stay in the closet as well as have worse outcomes with AIDS.

Fauci agreed the research was promising but cautioned that the connections between the neurological and immune system are extremely complex, and no single mechanism is likely to provide the entire answer.

Cole said a neurotransmitter called norepinephrine that is involved in stress reactions could be the link between social inhibition and worse prognosis in AIDS.

"It's squirted out of one neuron and is received by another neuron," Cole said. "This happens with such intensity that norepinephrine spills into the blood. That changes how your heart works. If we infect a cell with this, the virus grows 10-fold faster."

The next step would be to examine whether blocking norepinephrine affects the AIDS outcome, Cole said. Common heart medications called beta-blockers can keep the body from responding to the neurotransmitter.

"The nervous system communicates with the immune system," agreed Steven Douglas, chief immunologist at the Children's Hospital of Philadelphia, who has studied another neurotransmitter, Substance P, that appears to play a similar role linking depression with HIV infection. "That's what is so exciting."

Scientists are far from understanding all the links in the bewildering number of chemicals that establish feedback loops between the body and the brain, but teams of researchers at the intersection of neurology, immunology and endocrinology are working to chart all the pathways and signals.

Gold noted that stress is a normal response to threatening situations that has been learned through evolution -- stress forces the body to choose short-term performance over long-term health.

"It is not good to be lackadaisical if you are a rat being chased by a cat," he said. "There is a lot of circuitry in the brain that is organized to promote anxiety."

After the emergency is over, most people's internal chemical balance downshifts into a more sedate state. But in some people, Gold said, things don't scale down: "You are ready for stress, you are ready to bleed, you increase your glucose. That is not a good state to stay in for months or years. The bone breaks down; you get heart disease."

Gold said an important conclusion is that people with emotional disorders should be regularly monitored for osteoporosis and heart disease. And treating mental disorders, he said, could be a definite step toward slowing -- even preventing -- physical disease.

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