Blocking a protein in the brain that prevents neural stem cells from maturing may lead to a potential new way to treat depression, one of the most common mental disorders in the U.S.
After the gene that makes the protein, called sFRP3, was deleted in mice their brains behaved as though they were on antidepressants, researchers from Johns Hopkins University in Baltimore found. When sFRP3 is overactive, neural stem cells can't mature into neurons, a process that's been linked to the success of antidepressant treatments, according to the study published in the journal Cell Stem Cell.
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Research has shown that drugs that regulate the brain chemical serotonin, such as the selective serotonin reuptake inhibitors, a class that includes Eli Lilly & Co.'s Prozac, also work by removing the inhibition on neuron growth. That's part of the reason it can take as long as a month of treatment for patients to feel relief after they begin treatment, said Hongjun Song, a study author and director of the stem cell program at Johns Hopkins University School of Medicine.
"We know that newborn neuron development is important for antidepressant effects," Song said. "This links those two things together."
The findings suggest the protein could be targeted by either medications or electroconvulsive therapy. A previous paper from the group published online in the journal Molecular Psychiatry showed that mice that had been treated with ECT had less of this blocker protein than those not treated. In a group of people, certain variations on this gene predicted better responses to antidepressants.
"This may be a really good target for novel antidepressant treatments," Song said. And because the protein is expressed only in specific areas of the brain, targeting it may lead to medications with fewer side effects, he said.
His group also looked at a database of more than 500 depression patients, tracking their responses to drugs. Those with three underactive gene variants that produced sFRP3 responded better to antidepressant treatments, the group found. That may mean genetic testing could help predict a patient's response to antidepressant therapy.
Depression is among the most common mental disorders in the U.S., according to the National Institutes of Health. About 6.8 percent of the adult population, or 15.5 million people, had a major depressive episode that year, according to a 2010 survey.