Shyness Can Be Deadly

"Since ancient Greece, physicians have noticed that persons with a 'melancholic temperament' are more vulnerable to viral infections," said Steve Cole, principal investigator and assistant professor of hematology-oncology at the David Geffen School of Medicine and a member of the UCLA AIDS Institute.

"During the AIDS epidemic, researchers found that introverted people got sick and died sooner than extroverted people," said Bruce Naliboff, co-author and a clinical professor at the UCLA Neuropsychiatric Institute and Veterans Affairs Greater Los Angeles Healthcare System. "Our study pinpoints the biological mechanism that connects personality and disease."

The UCLA team studied the effect of stress on viral replication in a group of 54 HIV?infected men. All of the men were still in the early stages of the disease and in good health. Each possessed high T-cell counts with detectable levels of virus in the blood.

The researchers put each man through a series of stress tests in the lab to measure the response of their autonomic nervous system. First, the scientists monitored the subject's response to a tiny stimulus, such as an unexpected beeping sound. They measured his heart rate, skin moisture and dilation of the blood vessels, which contract during stress to reroute blood to the legs for fight or flight.

"Shy persons didn't adapt to the beeps as fast as other people," Cole said. "Their heightened nervous system response indicated that the sound was more irritating to them."

Next, each man was required to perform physical exercises, such as deep breathing or standing from a seated position, both of which require the nervous system to adapt quickly. Finally, scientists asked each man to perform rapid mental arithmetic, replying curtly if the subject provided the wrong answer and requiring him to start over.

To gauge the subject's overall "stress personality," the UCLA team ranked each man by totaling his nervous system's reactions during two physical and mental testing periods.

To assess the link between nervous system activity and HIV progression, for 12 to 18 months the scientists also monitored each man's HIV viral load and T-cells, which AIDS destroys.

During the evaluation period, some of the research subjects began antiretroviral drug therapy. The researchers studied these men's responses to the drugs by tracking their viral loads and T-cell counts. A boost in T-cells shows recovery from HIV on antiretroviral drugs.

"We found a strong linear relationship between personality and HIV replication rate in the body," Cole said. "Shy people with high stress responses possessed higher viral loads."

The researchers were surprised to find that the antiretroviral drugs barely made a dent in the shy patients' disease. Instead of showing lower viral loads, the immune systems of introverted subjects replicated the virus between 10 to 100 times as fast as in other patients.

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"Our findings suggest that high nervous system activity helps the virus continue replicating," Cole said. "Patients with high-stress personalities continued to lose T-cells -- even on the best drug therapy available. Stress sabotages their battle against this lethal disease."

"It looks as though sensitive people are simply wired to respond to stress more strongly than resilient people," Naliboff said. "How someone reacts to stress seems to be more important than the stress itself in explaining why one person gets sick and one person doesn't."

"This heightened stress response is the equivalent of waves striking a stone on the beach," Cole said. "One wave won't do much damage. But the constant pounding of waves eventually grinds that stone to sand. That's how continual stress response wears down the immune system."

Previously the UCLA team found that the body under stress releases a chemical called norepinephrine that leaves the T-cells open to infection and accelerates HIV replication. The researchers' next step will be to try and change shy persons' physiologic response to stress using drugs that block norepinephrine's impact on T-cells.

"Our current study suggests that the body's production of norepinephrine during stress makes a big difference in people trying to fight off infection," Cole said.

Margaret Kemeny, John Fahey and Jerome Zack co-authored the article. The National Institute of Allergy and Infectious Diseases, UCLA Center for AIDS Research, Universitywide AIDS Research Program, and Veterans Affairs Medical Research funded the study.