Some highly effective medications also happen to be highly mysterious. Such is the case with the antidepressant drugs known as selective serotonin reuptake inhibitors, or SSRIs: They are the most common treatment for major depression and have been around for more than 40 years, yet scientists still do not know exactly how they work.

Nor is it known why only two out of every three patients respond to SSRI treatment, or why it typically takes several weeks for the drugs to take effect—a significant shortcoming when you’re dealing with a disabling mood disorder that can lead to impaired sleep, loss of appetite, and even suicide.

New research by a team of Rockefeller scientists helps elucidate how SSRIs combat depression. Their work, published in Molecular Psychiatry, could one day make it possible to predict who will respond to SSRIs and who will not, and to reduce the amount of time it takes for the drugs to act.