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Combination of Stress, Low Serotonin may Promote Heart Disease

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Duke Health News 919-660-1306

DURHAM, N.C. -- The same brain chemical that influences
moods and personality traits like depression and hostility also
may influence a person's risk of heart disease, according to a
Duke University Medical Center researcher.

Duke psychologist Edward Suarez found that, when put under
emotional stress, people with low levels of the brain chemical
serotonin showed a significant rise in immune system proteins
known to contribute to heart disease. Subjects with normal or
high serotonin levels -- as measured by a breakdown product in
the blood called 5-HIAA -- did not show increased production of
these proteins under the same stressful conditions, the study
found.

Suarez said his study findings may explain why depressed and
hostile individuals, who often have low serotonin levels, die
more often from heart diseases and other illnesses that involve
a heightened immune system response.

Furthermore, he said, the findings hold the tantalizing
possibility that medications used to increase serotonin in the
treatment of depression could also be used to lower the risk of
heart disease.

Results of the study, funded by the National Heart, Lung and
Blood Institute, were prepared for presentation Saturday at the
annual meeting of the American Psychosomatic
Society
meeting in Savannah, Ga.

"We've long known that stress contributes to heart disease,
and that people with low serotonin have more heart disease,"
Suarez said in an interview. "Now we have shown that cellular
mechanisms suspected of contributing to atherosclerosis are
associated with a neurochemical, serotonin, which is associated
with depression and hostility.

"Specifically, our study showed that in people with low
levels of serotonin, stress activates the same immune system
response as do other environmental factors like high
cholesterol and smoking. But the stress response only occurs
among people with low serotonin."

In a study of 56 healthy men and women, Suarez and his
colleagues asked subjects to recall events in their lives that
made them sad or angry. Before and after each recollection, the
researchers analyzed their blood for the presence of certain
cytokines, proteins that white blood cells produce when they
are preparing to repair a site of injury. The presence of such
cytokines would indicate that the body was gearing up its
immune system, as it does in response to smoking, high
cholesterol, high blood pressure and other assaults.

When researchers tested the subjects prior to stress
testing, none of them showed an increase in cytokine activity,
regardless of their serotonin levels. However, when subjects
were asked to describe a sad or angry event, men with low
serotonin responded by producing higher levels of two cytokines
-- interleukin 1 alpha and tumor necrosis factor alpha. Suarez
said both cytokines are well recognized as contributing to
atherosclerosis, or a buildup of plaque in the arteries, which
can lead to a heart attack.

Interestingly, women with low serotonin showed an increase
only in interleukin 1 alpha, possibly due to the
anti-inflammatory effects of estrogen, Suarez said.

Men and women with normal or high levels of serotonin showed
no increase in cytokine activity during the sadness and anger
recall test. In all, five cytokines were measured.

"Our results suggest that, in people with low serotonin,
stress prompts the immune system to behave like there is an
injury in need of repair," Suarez said. "Once the immune system
is engaged, it activates white blood cells at the perceived
site of injury to begin their repair."

The very process of repair is what contributes to heart
disease, the researchers say.

Upon activation, white blood cells, or Amonocytes," stick to
the site of injury -- in this case, the artery walls of the
heart where assaults like smoking, high blood pressure and high
cholesterol have created microscopic tears. Once there, they
build up into layers, all the while consuming low density
lipoprotein, or the "bad" cholesterol. The very act of
consuming cholesterol creates a process called oxidation, in
which the cholesterol cells become hardened like cement. Hence,
plaque is formed inside the lining of artery wall, a process
commonly called "hardening of the arteries."

The researchers believe that stress initiates this process
by triggering the release of stress hormones, like adrenaline
and cortisol, which propel the immune system into action.

"Stress appears to be an environmental trigger that sets
into motion an immune response among people who have a
biological underpinning toward negative moods like depression,
hostility and aggression," Suarez said. "In other words, stress
mimics the response of an actual physical injury."

Suarez said the study findings support the prevailing view
of heart disease as an inflammatory response waged by the
immune system against the heart.

Lowering cholesterol and reducing stress have been mainstays
of heart disease prevention and treatment. Now, the researchers
believe, if subsequent studies confirm the results, that
boosting serotonin levels may be another effective method of
treating and preventing heart disease in susceptible
individuals.

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