Pick-me-ups? Without the growth of new neurons (blue) from brain stem cells (green), antidepressants don't work.

Antidepressants Need New Neurons to Work

New research is bolstering the idea that depression may be affected by the birth of new neurons. In studies with mice, published in the 8 August issue of Science, scientists report that antidepressants didn't work if neurogenesis was blocked.

The idea that neurogenesis and depression are linked is backed by several seemingly disconnected observations. Stress, which suppresses neurogenesis, can trigger bouts of depression. Certain brain regions in chronically depressed patients tend to be smaller than those of their nondepressed counterparts (ScienceNOW, 4 August). And antidepressant medications seem to promote neurogenesis, at least in mice. That last find inspired René Hen, Luca Santarelli, and Michael Saxe of Columbia University in New York City and their colleagues to test whether neurogenesis is necessary for depression drugs to do their job.

The researchers first tested the efficacy of antidepressants in rodents using a standard measure of depression and anxiety: how long it takes the animals to fetch food from a brightly lit area. After 4 weeks of treatment with antidepressants from either of two major drug families, once-reluctant mice retrieved food in a brightly lit area about 35% faster than those given a placebo. The bolder mice also had 60% more dividing cells in the hippocampus, which is involved in memory and learning and is a site of neurogenesis in the adult brain.

Then the researchers x-rayed the hippocampus to kill the stem cells that give rise to new neurons. Although similar to their untreated counterparts in a series of stress and learning tests, the irradiated mice differed in two important ways: Four weeks of treatment with antidepressants did not prompt the usual spurt of new neurons, and the drugs had no effect on the animals' reluctance to retrieve food pellets from brightly lit areas. However, the irradiated mice did not seem to be more anxious or depressed than control mice.

The experiments are the first to show a cause-and-effect relationship between the growth of neurons and depression, says neuroscientist Fred Gage of the Salk Institute in La Jolla, California. Although it does not clear up all the questions about the connection, he says, "it definitely supports the idea that neurogenesis is involved" in the disease.

Related sites
René Hen's home page
Fred Gage's home page