Antidepressant drugs may protect brain from damage due to depression

August 01, 2003

St. Louis, Aug. 1, 2003 -- Studying women with histories of clinical depression, investigators at Washington University School of Medicine in St. Louis found that the use of antidepressant drugs appears to protect a key brain structure often damaged by depression.

Previous research has shown that a region of the brain involved in learning and memory, called the hippocampus, is smaller in people who have been clinically depressed than in those who never have suffered a depressive episode. Now, researchers have found that this region is not quite as small in depressed patients who have taken antidepressant drugs.

The study, led by Yvette I. Sheline, M.D., associate professor of psychiatry, radiology and neurology, appears in the August issue of the American Journal of Psychiatry. The hippocampus is a part of the brain's limbic system, a group of structures important to emotion and motivation. Using high-resolution magnetic resonance imaging (MRI), Sheline's team measured hippocampal volumes in 38 women who had experienced an average of five episodes of major depression in their lifetimes. Only some of those episodes had been treated with antidepressant drugs.

"In addition to their brain scans, each woman was interviewed on two occasions by independent interviewers to determine how long each depressive episode lasted and how much, if any, of that episode was treated with antidepressants," Sheline says.

The team compared hippocampal volumes to the number of days on or off treatment. They found that on average, hippocampal volume was smaller than normal in depressed women, and that the less time a woman had spent taking antidepressants, the smaller her hippocampus. The amount of volume loss was predictable, based on the number of days depressed versus the number of days on antidepressant treatment.

"Our results suggest that if a woman takes antidepressants whenever she is depressed, depression would have less effect on the volume of her hippocampus," Sheline says. "It is the untreated days that seem to affect hippocampal volumes."

Animal studies also have demonstrated that antidepressant drugs can protect against stress-induced decreases in hippocampal volumes. Why the hippocampus shrinks is not clear. It may be that brain chemicals released during depression, such as cortisol, damage brain cells. Or it could be that depression damages the connections between nerve cells, resulting in a smaller volume. But however the damage is done, Sheline says it is clear from this study that antidepressant drugs can limit volume loss.

"We've shown in other studies that people with hippocampal damage also have problems with certain memory tests," she says. "And large epidemiology studies have shown that major depression is a risk factor for the later development of Alzheimer's disease. So it seems clear that volume loss in the hippocampus can have very negative effects, not to mention the devastating problems caused by depression itself."

Sheline and colleagues did not look at specific antidepressants to compare whether one was better than another at preserving hippocampal volumes, but any antidepressant seems to protect the brain better than no treatment.

Sheline says because volume loss in the hippocampus appears to be cumulative -- that is, the more episodes of depression, the more volume loss -- it is important to recognize and treat depression right away to prevent damage. It also may be worthwhile for patients to continue taking antidepressants between episodes of depression.

"Many psychiatrists already recommend that some patients who are prone to depression remain on antidepressants permanently to protect against depression," Sheline explains. "These apparent neuroprotective effects provide a further argument for at least strongly considering remaining on antidepressants."

Currently, Sheline's team is looking at whether antidepressant drugs prevent damage to hippocampal neurons or whether they may potentially restore previously lost volume. It is unclear whether drugs can restore volume that was lost, but she says this research demonstrates that without treatment, hippocampal volume loss in depressed patients was more extensive than it was in those who took antidepressant drugs.
Sheline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. The American Journal of Psychiatry, vol. 160:6, pp. 1516-1518, Aug. 1, 2003.

This research was supported by grants from the National Institute of Mental Health and the Division of Research Resources of the National Institutes of Health.

Washington University School of Medicine

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