Aug 1, 2003 — Optimism, motivation, and hope aren’t the only things stunted by depression. So is the size of a specific region of the brain.

Researchers have long known that the hippocampus, a part of the brain involved in learning and memory, is usually smaller in people with a history of depression than in those without the disease. But new research suggests that depressed patients who continue to take antidepressant medication — even when they’re feeling better — may be more likely to minimize or possibly prevent this shrinkage.

Using MRIs, scientists at Washington University School of Medicine measured the size of the hippocampus in 76 women — half had repeated bouts of major depression while the others had no history of depression. Not only did the researchers find that the depressed women had a smaller hippocampus, but its size was largely determined by how long they continued their medication. The less time spent on medication, the greater the shrinkage.

The Longer the Medication, the More Protection

“The take-home message is that not only do antidepressants help prevent relapse of depression in patients with a history of recurrent depression, but they also appear to protect against brain volume loss associated with depression,” researcher Yvette I. Sheline, MD, tells WebMD.

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

Only women were studied because statistically, they are twice as vulnerable to depression as men, and Sheline focused only on their medication usage — and not other important treatments such as psychotherapy.

Her study — published in the August issue of the American Journal of Psychiatry — is especially important because patients with major depression are prone to relapses even after long-term antidepressant treatment and others discontinue their medications once symptoms subside.

Most experts recommend treatment with antidepressants for at least six months — and usually longer — to prevent relapse. But a study last February in the American Journal of Managed Care indicates thatmany patients stop taking their medication within three months, and it’s these patients who face a great likelihood of a relapse.

Learning and Memory Brain Region

Why this hippocampus shrinkage occurs in people with depression is not clearly established, but there are two prevailing theories: Either stress hormones such as cortisol released during a depressive episode damage brain cells or the disease destroys connections between nerve cells.

Although this part of the brain is not directly involved in mood, Sheline says it is closely tied to another part of the brain that is. The hippocampus is more closely associated with learning and memory skills, and previous research suggests that depressed people tend to score lower on certain memory tests, especially those tied to verbal abilities.

Bruce S. McEwen, PhD, the researcher credited as being the first to discover that the hippocampus has receptors for stress hormones that can damage it, says that Sheline’s study is significant. He directs a neuroendocrinology laboratory at The Rockefeller University in New York, a leading biomedical research facility.

“She’s certainly the leader in showing that the hippocampus shrinks with prolonged depressive illness and now, this study suggests that maybe you can do something about it,” he tells WebMD.

“In the first episode of depression, there doesn’t seem to be a smaller hippocampus, so this shrinkage has to develop over time. In our animal studies, we found that you can reverse these changes if you stop the stress up to a certain point.”

Antidepressant medications can do that by controlling the release of stress hormones such as cortisol. “But there’s also evidence that these medications increase cell proliferation in certain brain regions, and one of the attractive mechanisms is an enhancement of a new generation of new nerve cells, which are being replaced all the time in this part of the hippocampus,” McEwen says.

Sheline is now trying to determine whether continued treatment with antidepressants can actually restore the hippocampus to “normal” size. In her current study, she did not investigate whether any specific medications were more effective than others; all seem to protect the brain better than no treatment, she says.