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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”


Why HIV Kills More Shy People

Dwayne Hunter

Betterhumans Staff

Monday, December 15, 2003, 4:31:26 PM CT




Personality influences the immune system's ability to fight off diseases such as AIDS, and now researchers have found why shy people are at greater risk.

The researchers, from the University of California, Los Angeles, have identified a mechanism linking the way people react to stress with their ability to resist infection.

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

Ill introverts


Cole and colleagues identified the immune mechanism that makes shy people more susceptible to infection than outgoing people.

"During the AIDS epidemic, researchers found that introverted people got sick and died sooner than extroverted people," says Bruce Naliboff, coauthor of the research and a clinical professor at the UCLA Neuropsychiatric Institute. "Our study pinpoints the biological mechanism that connects personality and disease."

To identify the mechanism, the researchers examined a group of 54 HIV infected men, all still in the early stages of the disease and in good health, to determine the effects of stress on viral replication.

The researchers administered a series of stress tests in the lab to measure the response of the men's autonomic system.

They measured response to stimuli such as an unexpected beeping sound, checking heart rate, skin moisture and dilation of blood vessels, which contract during stress to reroute blood to the legs for fighting or fleeing.

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

In the next test, the men were asked to perform physical exercises such as deep breathing or standing from a seated position—both of which require the nervous system to quickly adapt.

The last test required the men to perform rapid mental arithmetic while the scientists would reply curtly to a wrong answer and require subjects to start over.

Stressed sicker

The researchers ranked participants by totaling their nervous system reactions during physical and mental tests to gauge their "stress personality."

They measured the link between nervous system activity and HIV progression by monitoring HIV viral load and T cells over a 12- to 18-month period.

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

The correlation was so profound, the researchers were surprised to find, that antiretroviral drugs barely had an impact in shy patients. HIV replicated 10 to 100 times as fast in infected introverts compared to others taking the drugs.

"Our findings suggest that high nervous system activity helps the virus continue replicating," Cole says. "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."


Psychological risk factors for HIV pathogenesis: mediation by the autonomic nervous system

Steve W. Cole, Margaret E. Kemeny , John L. Fahey, Jerome A. Zack and Bruce D. Naliboff

a Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA (SWC, JAZ)
b Departments of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA (JLF, JAZ)
c Department of Psychiatry and Biobehavioral Sciences (BDN), University of California, Los Angeles, Los Angeles, California, USA
d AIDS Institute (SWC, JLF, JAZ), University of California, Los Angeles, Los Angeles, California, USA
e Department of Psychiatry (MEK), University of California, San Francisco, California, USA
f Department of Veterans Affairs Greater Los Angeles Area Healthcare System (BDN), Los Angeles, California, USA

Received 8 July 2002;  revised 24 October 2002;  accepted 1 November 2002. ; Available online 11 April 2003.



Epidemiologic studies have identified psychological risk factors for specific physical diseases, but the biological mechanisms mediating these relationships remain poorly defined.


Social inhibition and autonomic nervous system (ANS) activity were assessed on multiple occasions in 54 gay men with asymptomatic human immunodeficiency virus (HIV) infection. Following baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were monitored for 12–18 months to assess relationships between ANS activity and HIV pathogenesis.


We confirmed the previously reported relationship between socially inhibited temperament and vulnerability to viral pathology. Plasma viral load set-point was elevated eight-fold in socially inhibited individuals, and these individuals showed poorer virologic and immunologic response to initiation of highly active antiretroviral therapy (HAART). Effects were independent of duration of infection, HAART regimen, demographic characteristics, and health-relevant behavior. Neurophysiologic assessments documented elevated ANS activity in socially inhibited individuals, and mediational analyses showed that such differences could account for 64%–92% of the covariance between social inhibition and virologic parameters.


These data provide the first clinical evidence that differential neural activity mediates relationships between psychological risk factors and infectious disease pathogenesis. Such findings also suggest novel targets for adjunctive therapy in long-term control of HIV-1 disease.

Author Keywords: Temperament; autonomic nervous system; viral pathogenesis; human immunodeficiency virus; psychoneuroimmunology