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Could Lack of Neuron Growth Factor Explain Why People Get Depressed?

A young psychiatric researcher and her colleagues have found a way to remove a gene from the brains of adult animals that makes brain-derived neurotrophin factor. They appear to be the first scientists to have successfully knocked out any kind of gene in the brains of adult animals.

In 1986 an Italian scientist, Rita Levi-Montalcini, M.D., won a Nobel Prize in Medicine for the discovery of nerve growth factor. Since then, a number of factors have been found to influence the growth of neurons in the brain, and one of the most prevalent appears to be brain-derived neurotrophin factor.

Lisa Monteggia, Ph.D., has made a notable advance in the neurotrophic growth factor arena that will likely benefit psychiatric illness research.

Now a young American scientist—Lisa Monteggia, Ph.D., an assistant professor of psychiatry at the University of Texas Southwestern Medical Center at Dallas—and her colleagues appear to have made a notable advance in the neurotrophic growth factor arena. They have found a way to eliminate the gene for brain-derived neurotrophin factor from the brains of adult mice.

Monteggia announced their achievement at the 14th Annual Scientific Symposium of the National Alliance for Research on Schizophrenia and Depression in New York City in October. She and her colleagues will soon be submitting a paper to a scientific journal describing the details of their technique.

Now that Monteggia and her colleagues can knock out the gene for brain-derived neurotrophin factor, she explained at the symposium, they are going to use mice lacking this gene to explore the factor’s possible involvement in depression. For instance, they are going to see whether mice without the gene for the factor, and thus without the factor itself, appear to be depressed. If they are, it would suggest that lack of brain-derived neurotrophin factor, or at least an insufficient amount of it, might play a role in depression.

In fact, there is already some evidence that an insufficient amount of the factor is involved in depression. For instance, antidepressant treatment has been found to increase the factor in the hippocampal region of the brain—a brain region increasingly implicated in depression (Psychiatric News, August 16).

The ability of Monteggia and her team to eliminate the gene for brain-derived neurotrophic factor from the brains of adult mice appears to have wider implications. As Monteggia explained at the symposium, "This appears to be the first report of any system that can successfully knock out a gene in the brains of adult animals."

Lewis Judd, M.D., chair of psychiatry at the University of California at San Diego, not only agreed with her statement at the symposium, but amplified it: "This is really a stupendous piece of work technically. I can’t tell you how many people have tried to do such a thing but failed."

In fact, once genes implicated in various psychiatric disorders are identified, the system could probably be used to knock out those genes in adult mice, Monteggia told Psychiatric News. Then the mice could be used to study how those particular genes cause psychiatric illness.

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