Antidepressant drugs may protect brain from damage

Studying women with histories of clinical depression, School of Medicine investigators 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.

Dr. Sheline with patinet Young
Yvette Sheline, M.D., professor of psychiatry, treats 94-year-old Cleordia Young, a longtime patient who has been treated for depression at the School of Medicine for more than 40 years.

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, of radiology and of 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, 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 said.

The team compared hippocampal volumes to the number of days on or off treatment. The researchers 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.

“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 said. “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 said 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 said. “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 said 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 said. “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 said this research demonstrates that without treatment, hippocampal volume loss in depressed patients was more extensive than it was in those who took antidepressant drugs.

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