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Study Sheds Light on How Depression Drugs Work

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Study Sheds Light on How Depression Drugs Work


Study Sheds Light on How Depression Drugs Work

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  • <iframe src="" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
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Scientists have discovered a protein in the brain that may explain how drugs like Prozac fight depression and why they take so long to work. The finding could also point the way to a new generation of drugs for depression. NPR's Jon Hamilton explains.

JON HAMILTON reporting:

Trevor Sharp of the University of Oxford in Great Britain says what scientists know about drugs like Prozac is that they almost immediately increase the amount of serotonin that's available to brain cells. So you'd think people would get happier right away.

Mr. TREVOR SHARP (University of Oxford): And yet it's well-known from many, many studies that the drugs don't produce the therapeutic phase, they don't relieve depression in patients until patients have been taking a course of these drugs for several weeks.

HAMILTON: So researchers began looking at precisely how serotonin acts on brain cells. That's hard to do in people. Instead, Per Svenningsson of the Karolinska Institute in Stockholm turned to depressed mice. How can you tell if a mouse is depressed? Svenningsson says there are several ways.

Mr. PER SVENNINGSSON (Karolinska Institute): The test that I used is called the tail suspension test. So you hang the mouse in the tail and then they struggle.

HAMILTON: Depressed mice struggle less than normal mice. But give them an antidepressant drug and after a period of time they start to fight harder. Svenningsson and a group of US scientists identified a molecule that seems to make mouse brain cells more sensitive to the feel-good effects of serotonin. The molecule is called p11. Mice that lacked p11 acted depressed. Those with normal amounts didn't.

Mr. SVENNINGSSON: The effect that we saw in this mouse model is very dramatic.

HAMILTON: And Svenningsson says levels of p11 rose when the mice got drugs for depression, but it took quite a while.

Mr. PAUL GREENGARD (Rockefeller University): What this discovery showed was that p11 plays a major role in mood.

HAMILTON: Presumably by helping the cells respond more efficiently to serotonin. Paul Greengard of Rockefeller University is part of the team studying p11. He also won a share of the Nobel Prize a few years ago for his work on how signals travel through the brain. Greengard says if p11 has the same effect in humans as it does in mice, that may explain why current antidepressant drugs take so long to work. And, he says, there is evidence that p11 plays a role in human moods. Brain tissue from autopsies of people who had been diagnosed with depression contained less p11 than normal brain samples.

Mr. GREENGARD: Our thinking is that many subclasses of depression might be associated with lower levels of p11, on the one hand, and that raising either the level or the functionality of the p11 would be a novel way to develop antidepressants.

HAMILTON: Right now, there aren't any drugs that act directly on p11, but researchers say biotech companies are likely to start looking. Dr. Thomas Insel directs the National Institute of Mental Health. He's pretty excited about the new study.

Dr. THOMAS INSEL (Director, National Institute of Mental Health): This is quite important because it now focuses us on a whole new area and a whole new part of the cascade for how information gets processed in the brain.

HAMILTON: Insel says it's possible that drugs acting directly on p11 or some other crucial molecule could work as quickly as, say, painkillers.

Dr. INSEL: I don't know anybody with acute pain who would accept a drug that would take six to eight weeks to work, and certainly we shouldn't be expecting people with a disease as painful as major depressive disorder to have to wait that long to get a response.

HAMILTON: The new research on p11 appears in this week's issue of the journal Science. Jon Hamilton, NPR News.

MELISSA BLOCK (Host): This is NPR, National Public Radio.

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