Continued use of antidepressants leads to new cell growth in an area of the brain known to suffer cell death and atrophy as a result of depression and stress, a study by Yale researchers shows.

Chronic administration of antidepressants increases the number of neurons in the adult hippocampus, which could help explain how antidepressants produce their therapeutic response, according to Ronald S. Duman, Ph.D., professor of psychiatry and pharmacology. Duman was senior author of the study, published Dec. 15 in The Journal of Neuroscience.

The hippocampus is the part of the limbic brain that is involved in learning, memory, mood and emotion. It is one of only a few regions of the adult brain where production of neurons occurs in animals, including humans. Previous studies have demonstrated that stressful experiences, both physical and psychological, lead to neuronal loss in the hippocampus and that antidepressants can block this cell loss.

Duman’s laboratory has been studying the mechanism of action of antidepressants in rodents for over 15 years. The researchers have focused on cellular actions of antidepressants, looking at the role of the intracellular signal transduction pathways that control neuronal function. They have identified several actions of antidepressants that indicate that they influence the survival or the number of neurons in the hippocampus.

This study was intended to look at whether antidepressants increased the birth of neurons in the hippocampus. The researchers tested several different classes of antidepressant drugs, as well as electroconvulsive seizure therapy (ECS) and an antipsychotic medication.

ECS is clinically the most effective treatment for cases of depression that are resistant to available drug treatments. As expected, repeated administration of ECS increased the number of neurons in the hippocampus of the brain by 50 percent. The chemical antidepressants tested increased the number of neurons in the same area by 20 percent to 40 percent. The antidepressants that were administered included a monoamine oxidase inhibitor (tranylcypromine), a serotonin-selective reuptake inhibitor (fluoxetine) and a norepinephrine-selective reuptake inhibitor (reboxetine).

Acute administration of the antidepressants (one to five days) did not lead to any significant cell change. Results were seen after 14 to 28 days of administration, which is consistent with treatment regimens for the therapeutic response to antidepressants. These studies suggest that increased neuro-genesis in the hippocampus could counter the effects of stress on hippocampal atrophy and contribute to the actions of antidepressant treatments.