Combination of Stress, Low Serotonin may Promote Heart Disease

Duke University Medical Center
Saturday, 4 March 2000

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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