Researchers Discover a Brain Pathway That Could Lead to Better Antidepressants

A team of scientists has found a chemical pathway in the brain that reduces symptoms of depression when blocked. The findings may lead to the development of new treatments for depression, potentially helping patients who haven’t responded to traditional medications. The details are in a paper that was just published in the journal Molecular Psychiatry.

Major depressive disorder, or depression, affects millions of Americans each year. Therapy and medication can help manage symptoms but some people don’t respond to traditional treatments. Currently available antidepressants, for example, only work on part of the population. There is a significant need for alternative treatments and that was the focus of this new study.

Researchers from Northwestern University first aimed to investigate the mechanisms involved with known antidepressant drugs. By understanding how current medications work, the team hoped to find therapeutic targets for developing new treatments.

The team discovered that tricyclic antidepressant drugs, including Prozac, target a pathway called the BMP signaling pathway. The pathway is in the hippocampus, a part of the brain associated with memory formation. When the pathway is blocked by tricyclic drugs, stem cells are induced to grow into new neurons. These neurons affect mood and memory functions. The research team confirmed their discovery by using a protein called Noggin. Noggin only blocks the BMP pathway, while drugs such as Prozac affect multiple brain mechanisms. By testing whether or not Noggin reduced depression symptoms in mice, the team could verify that tricyclics were effective due to their action on the BMP pathway.

The researchers injected Noggin into depressed laboratory mice. They found that Noggin had significant antidepressant properties. Treated mice were more likely to fight back when being held by their tails (depressed mice gave up). Mice that had been treated with Noggin also showed less anxiety in mazes that contained open, unsafe spaces.

The team’s findings have helped identify a target for new antidepressant treatments, the BMP signaling pathway. Many patients fail to respond to traditional antidepressants, making this type of research critical.


Brooker et al. Hippocampal bone morphogenetic protein signaling mediates behavioral effects of antidepressant treatment. Molecular Psychiatry (2016).

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