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In recent years, researchers have discovered tantalizing evidence that antidepressants combat depression by promoting neurogenesis, the growth of new neurons in the brain. The evidence derives from several striking observations. One is that stressed monkeys grow fewer new cells in the hippocampus region of the brain than their healthy counterparts do. Secondly, most depression treatments, from drugs such as Prozac to a type of powerful magnetic stimulation, increase new neuron growth by up to 75 percent in rodents.

And in the most telling study to date, scientists from Columbia University and Yale University directed radiation at the hippocampi of mice to prevent neurogenesis. When given fluoxetine, also known as Prozac, the mice exhibited none of the behavioral changes normally associated with the drug. If neurogenesis is required to kick depression, as the result suggested, maybe its loss sends the mind into a tailspin. "It's a very appealing idea," comments Eric Nestler of the University of Texas Southwestern Medical Center at Dallas. "It provides a mechanism to explain why many cases of depression are chronic and progressive." It would also explain why Prozac takes a few weeks to exert its effects. The growth of neurons from stem cells takes a few weeks as well.

But the details nag at some researchers. Fritz Henn of Brookhaven National Laboratory says he was captivated by the idea early on. "I thought it was a good target for a final common pathway" underlying all forms of depression. But when Henn and his colleagues randomly shocked the feet of mice--a treatment that is known to erode neurogenesis--not all of the animals became depressed. "That experiment made me leery," he says. When neurogenesis is abridged by other means, such as irradiation, the animals do not all go on to show signs of depression, which suggests that the loss of neurogenesis is not sufficient to induce the illness, he notes. The big problem in teasing out the role of neurogenesis is that researchers lack a way of specifically increasing or decreasing the growth rate of neurons. To resolve this debate, Henn says, "somebody needs to come up with a clever experiment."

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