For the more than 18 million Americans who suffer from depressive illnesses, the best pharmacological treatments are those that increase levels of serotonin, the brain chemical that regulates mood, sleep and memory.
New research by an international team of scientists, led by Rockefeller University researchers in Paul Greengard's laboratory of Molecular and Cellular Neuroscience, shows that a gene called p11 is closely related to serotonin transmission in the brain -- and may play a key role in determining a person's susceptibility to depression.
The newly discovered link between depression and the serotonin system, reported in the January 6 issue of the journal Science, could lead to new treatments for these mental disorders.
"We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression," says Per Svenningsson, a research assistant professor and first-author on the paper. "Our findings demonstrate that patients with depression, and mice that model this disease, have decreased levels of p11 protein, and they suggest that drugs that increase p11 are likely to have anti-depressant properties."
Serotonin binds to 14 different receptors on a cell's surface. One receptor in particular, known as 1B, plays a crucial role in regulating serotonin transmission in the brain. Recent studies have suggested a role for the serotonin 1B receptor in depression, as well as in obsessive-compulsive disorder, drug addiction, anxiety, aggression and sleep.
Intrigued by these studies, Svenningsson and colleagues at Rockefeller, the Karolinska Institute, the University of Rouen in France and Eli Lilly and Company, used a blind screen called a yeast two-hybrid screen to identify proteins that associate with the serotonin 1B receptor. They found an association with a protein called p11, a protein previously identified as a regulator of the localization of several proteins on the cell's surface.
The researchers analyzed tissue from a mouse model of depression as well as post-mortem tissue from depressed human patients, and found decreased levels of p11 protein in both cases. On the other hand, p11 levels increased in rats and mice that were treated with anti-depressant medications or electroconvulsive therapy.