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Research Explores Link Between Stress and Depression

Do the stresses of everyday living take their toll on our health? With a $1.1 million grant from the National Institute of Mental Health (NIMH), a researcher at Wake Forest University Baptist Medical Center is exploring a possible link between stress and depression, hoping to find answers to help the 18 million Americans affected by the disease.

In a five-year study of female monkeys, Carol Shively, Ph.D., will look at how chronic, low-level stress affects brain function and can possibly lead to depression and other health problems.

"I believe the results will help us understand depression better," said Shively, professor of comparative medicine. "We want to know why some individuals are more likely to succumb to depression than others. What is it that puts them at risk?"

In earlier research, Shively and colleagues found a link between low-level stress and possible health problems. Female animals that were socially stressed – because they were in subordinate roles in their group – produced reduced amounts of the hormone estrogen and many showed signs of depression. In women, estrogen protects against heart disease, helps prevent bone loss and may also be associated with memory and depression.

"From the monkey studies, we know stress can lower estrogen levels to the point that health is affected, but the animals still have menstrual periods," said Shively. "This implies that some women may be producing less estrogen than they need and aren''t aware of it. Low estrogen levels could affect their hearts and bones and could also cause depression."

In the earlier research, Shively found that monkeys under stress had changes in the way their brains produced and used the chemicals responsible for transmitting nerve impulses. NIMH research has shown that these chemicals are also out of balance in depressed humans.

In the current study, Shively wants to learn more about these changes in brain function in

hopes of finding a clue about why some individuals may be more susceptible to depression than others.

The study will use positron emission tomography (PET) scanning, a technique that produces three-dimensional images of the brain''s chemical activity. The researchers will evaluate the hormonal system that regulates the body''s response to stress, which is overactive in many patients with depression. The animals'' brains will be imaged before the experiment begins and at various points as they are exposed to social stress.

"We''re going to look at their brain function both before and after their social status changes," said Shively. "We will determine whether there was something about them that was different before they were exposed to social stress. If there is, it might help predict depression risk in humans."

The research will provide answers not possible through human studies. Monkeys have a natural tendency to order themselves in a social hierarchy that proves stressful for low-level monkeys. The monkeys that tend to "win" confrontations with their cage mates are called "dominants" by researchers. The "subordinate" monkeys receive little grooming or other friendly contact from their cage mates, spend more time alone, and are subject to aggression by the dominant monkeys.

In the current study, subordinate monkeys that develop depression will be treated with the same anti-depressant drugs prescribed for depressed people. The final phase of research will be to determine if the drugs reversed changes in brain function that occurred because of social stress. Shively says the information may help physicians learn more about treating depression in humans.

"We almost never study people who are undergoing their first depression and have never been medicated. We don''t know much about brain function before and after treatment," said Shively.

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