By LAURAN NEERGAARD
Monday, October 1, 2001
AP MEDICAL WRITER
WASHINGTON -- A study of primates' brains says a European drug seems to counter a worrisome side effect of major depression - the shrinking of an important region of the brain.
The study is raising calls for further research to see if more widely used medications might help, too.
"These are impressive and important findings," said Dr. Robert Sapolsky of Stanford University, who reviewed the new research, published in Tuesday's Proceedings of the National Academy of Sciences.
But, "mind you, this is one antidepressant and this is a fairly atypical one" compared to the antidepressants most Americans use, Sapolsky cautioned.
German researchers tested a new antidepressant sold only in Europe called tianeptine. The antidepressants most popular in the United States - Prozac and similar medications - work by blocking the dissipation of a neurotransmitter called serotonin that's important for mood. Tianeptine does exactly the opposite, enhancing serotonin uptake.
Major, long-term depression can cause a brain region called the hippocampus to shrink, in some cases nearly 20 percent. The hippocampus is important for learning and memory, so that probably explains why memory loss often accompanies depression. And the region doesn't seem to bounce back after the depression is cured.
Nobody knows exactly why this atrophy occurs: Neurons may die or shrink, or ones that should have been born to replenish the region may not be. Whichever, it does seem linked to a stress hormone called cortisol, because about half of seriously depressed patients secrete too much cortisol.
To see if tianeptine could help, neurobiologist Eberhard Fuchs and colleagues at the German Primate Center tested tree shrews, who exhibit a classic model for human depression when exposed to social stress.
Over the 35-day study period, depressed shrews experienced excess cortisol, decreased amounts of brain chemicals important for healthy cells, a 33 percent decrease in new cell growth and a 7 percent decline in hippocampal volume. But shrews that were given oral tianeptine saw their brain chemical concentrations return to normal, cell growth restart and the hippocampus return to its pre-depression size.
"This increase produced by tianeptine suggests that hippocampal volume loss in depressed humans could possibly be prevented by antidepressants," Fuchs concluded.
Most intriguing, tianeptine worked without lowering the amount of stress-caused cortisol, said Dr. Jeffery Barker of the National Institutes of Health, whose laboratory studies how neurotransmitters and other chemicals create brain tissue. That suggests the drug blocked cortisol's bad effects downstream.
"It's extremely well-done" research, Barker said. But he cautioned that much more research is needed to tell if tianeptine, let alone different-acting antidepressants, might offer similar protection to people.
Indeed, the studies that discovered hippocampal shrinkage were done on people who had recovered from depression after the use of older medications, Sapolsky said. No one has yet studied newer antidepressants. Nor has tianeptine prompted much excitement among U.S. psychiatrists, because reports from Europe suggest it's not very effective, he said.
"It would be a boon ... if any antidepressants can prevent some of the neurobiological correlates of depression, in addition to alleviating the affective symptoms," he wrote in an article accompanying the research. Still, the findings "support the frequent uphill battle" for patients, "namely, convincing others that this is a real biological disorder, rather than some sort of failure of fortitude or spirit."