New research into depression is showing that antidepressants are not only changing the chemicals inside the brain, they actually make the brain grow new cells. As this ScienCentral News video reports, the new findings may lead to improved treatments against depression.
Antidepressants make your brain grow
One in ten adults suffers from depression in any given year. Many of them get relief from antidepressants, but they usually take a long time to work and often have troubling side effects. Now a study at Columbia University shows that these drugs don't work the way scientists have thought.
Neuroscientists have long believed that a shortage of a brain chemical called serotonin causes depression, so most antidepressants were tailored to raise serotonin levels in the brain. But some researchers have suspected that antidepressants do more than that. Together with his coworkers, René Hen, professor of pharmacology at Columbia, has now proven that antidepressants actually stimulate the growth of new brain cells, which turns out to be necessary for recovery from depression.
Hen studied the effects of antidepressants in mice, and focused on a part of the brain, called the hippocampus, that regulates moods.
His researchers tested the behavior of a type of mouse that is bred to be depressed from birth. They measured the time it takes for these mice to eat a food pellet that's placed in an intimidating environment— a bright open space. Animals that have been given antidepressants for a few weeks are less intimidated by the aversive test setup, and hesitate for a shorter time before they start eating. The drugs have relieved their depression.
To look at the difference in brain growth for treated mice, Hen's collaborators exposed some of them to x-rays aimed specifically at the hippocampus. The radiation, which caused a white stripe in the fur across their heads, blocked the mice's ability to grow new cells in the hippocampus. Irradiated mice given the same antidepressant treatment as the first group took longer to approach the food, even though they were hungry. Because the animals couldn't grow new cells in the hippocampus, the drugs had no effect on them.
"Even though the mice look normal after being irradiated, they now no longer respond to antidepressants," Hen says.
Hen thinks that antidepressants have the same effect in people, and that the findings will lead to new and better treatments for depression. "There are two hopes basically. One is that we are going to have drugs that work faster, and the other one is that we are going to have drugs that work with less side effects."
It often takes a month or more for popular antidepressants to reach full therapeutic effect. Hen says the drugs start a series of reactions in the brain, and the growth of new cells in the hippocampus comes late in that chain, and therefore the effect is delayed. Drugs that directly stimulate the growth of brain cells would have a quicker response, Hen thinks, and give faster relief to depressed people. To test this idea, he will give his mice compounds that are known to work this way. If they relieve symptoms of depression in animals, the compounds may be tested as drugs to treat people.
Because everybody's brain is a little bit different, Hen thinks that the response to antidepressants will never work with the same result in all depressed people. "We don't have a very objective way to diagnose depression. It's likely that once we understand the mechanism, it's going to be divided, just like other psychiatric disorders, into many disorders. And the rational classification may come from genetics," Hen says.
Additional applications
The hippocampus (in yellow).
In addition to mood control, the hippocampus plays important roles in learning and memory. Drugs that stimulate growth in this part of the brain may thus also have effects on these functions. "If you increase the number of new cells in the hippocampus of these animals, you also change the ability to learn mazes and spatial learning tests," Hen says.
The new cells that the hippocampus produces come from stem cells in the brain. In response to the antidepressants, these start to divide and then mature into functional brain cells. Biomedical researchers are learning how to harness the potential of these dormant stem cells, and allow them to differentiate into various neurons.
If neuroscientists learn how to wake up dormant stem cells in the brain and nervous system, the technique could lead to treatments of other diseases of the brain, such as Alzheimer's and Parkinson's disease, Hen says.
Hen's research, which was reported in the journal Science, was funded by the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Alliance for Research on Schizophrenia and Depression.
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