Deconstructing depression

Depression is believed to involve defects in serotonin signaling in the brain, but the details remain murky. Rockefeller University neuroscientist and Nobel Laureate Paul Greengard and his colleagues have now uncovered some of the specifics (Science 2006, 311, 77). The researchers searched for proteins that bind to the serotonin receptor 5-HT_1B and identified the neural protein p11 as a likely candidate. The team then determined that low levels of p11 in mice and humans are associated with depression. When the researchers provided mice with antidepressants, the animals' p11 levels increased. In other tests, p11 overexpression alleviated depression symptoms. The researchers also observed that higher levels of the protein increase the number of serotonin receptors on the surface of neurons, enhancing serotonin signaling. The findings could conceivably lead to a better understanding of depression and more effective ways to treat the condition.