Although antidepressants continue to be prescribed for those dealing with depression, they are believed to relieve symptoms in only 50 percent of patients. Now, a new study recently summarized in Science Daily suggests that the excess of one type of serotonin receptor in the center of the brain may be the cause. The study, conducted by researchers at Columbia University Medical Center, is the first to find a causal link between receptor number and antidepressant treatment. It is expected this study could lead to more personalized treatment for depression. Led by Rene Hen, PhD, professor of pharmacology in the Departments of Psychiatry and Neuroscience at Columbia University, the research report highlights that most antidepressants work by increasing the amount of serotonin made by cells called raphe neurons, deep in the middle of the brain. When depression is shipped to other brain regions, serotonin relieves symptoms of depression. Too many receptors of the 1A type on the raphe neurons creates a negative feedback loop that can reduce the production of serotonin. “The more antidepressants try to increase serotonin production, the less serotonin the neurons actually produce, and behavior in mice does not change,” Dr. Hen said. The effect of antidepressants was measured with a commonly used behavioral test that tests the boldness in mice when retrieving food from bright open areas. Mice on antidepressants usually become more daring. The drugs had no effect on the mice with a surplus of serotonin receptors. With new techniques in genetic engineering, Dr. Hen has created a strain of mouse that can be programmed to produce high or low levels of serotonin receptors of the 1A type only in the raphe neuron. These levels mimicked the levels found in people who are resistant to antidepressant treatment. “By simply tweaking the number of receptors down, we were able to transform a non-responder into a responder,” Dr. Hen added.
