Stress Causes a Supressed Immune System
to Weaken Resistance to Illness
By Shankar Vedantam
Washington Post Staff
Monday, December 22, 2003; Page
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
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,
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
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
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
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
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
"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