How Anti-Depressants Create

New Haven, Conn. — Antidepressants increase the presence of a growth factor in the brain, which then leads to a proliferation of new cells, according to a study by Yale School of Medicine researchers in this week’s Proceedings of the National Academy of Sciences.

The study describes for the first time the molecular mechanisms and the identity of the protein, vascular endothelial growth factor (VEGF), which underlie the actions of antidepressants on new cell growth and behavior.

“One in five Americans have depression, yet the neural mechanisms underlying depression and the actions of antidepressants remain unknown,” said Ronald Duman, senior author and professor of psychiatry at Yale. “These findings provide important, fundamental, and new information on the actions of these highly prescribed drugs. The data also has implications for understanding many stress related disorders.”

Duman and Jennifer Warner-Schmidt, a former graduate student at Yale now at the Rockefeller Institute, found in a rodent study that VEGF levels are increased by chronic administration of either of two major classes of antidepressant medications. Conversely, blocking the effects of VEGF prevents new cell birth in response to the medications.

Duman said recent studies demonstrated that stress decreases the expression of VEGF in the hippocampus, a region of the brain involved in the control of emotion, mood, learning, and memory, and this could contribute to the atrophy and loss of cells caused by stress and depression.

In prior groundbreaking research Duman found that antidepressants increase the expression of growth factors in the hippocampus and other regions of the brain. Duman also found that antidepressants increase the birth of new neurons in the hippocampus.

According to Duman, future studies could look at VEGF and related pathways for genetic mutations that might contribute to depression, or make a person more susceptible to depression. VEGF signaling also could provide targets for the development of novel, faster acting, and more effective therapeutic agents.