Brain & Behavior Research Foundation Grantee Xiang Cai, Ph.D., used his NARSAD Young Investigator Grant to study malfunction in communication between brain cells as a potential cause of depression. Instead of focusing on the levels of hormone-like chemicals in the brain, such as serotonin, the scientists found that the transmission of excitatory signals between cells becomes abnormal in depression. The findings of this new work were published online on March 17 in Nature Neuroscience.

Shedding new light on the role of serotonin in the brain is international news. “Some people say that depression is caused by a lack of communication,” stated The Voice of Russia yesterday on the findings by Dr. Cai, Assistant Professor, Department of Physiology, Southern Illinois University, “Now, the new study shows that this may even be true at the neurological level.”

For more than 50 years most antidepressants have been developed to increase concentrations of serotonin in the brain, but these therapies are only effective for approximately 50% of patients. This new research identifies for the first time a different role of serotonin in the brain—that of strengthening the communication between brain cells.  

In animal models, the researchers compared the brains of “normal” rats with “stressed” rats exhibiting the depressive state of anhedonia, or the inability to experience pleasure. They found that stress did not affect the levels of serotonin in the “depressed” brains, but rather the excitatory connections responded to serotonin in a strikingly different manner than in the “normal” brains. These changes could be reversed by treating the stressed animals with antidepressants. The researchers found that it was the ability of serotonin to strengthen excitatory connections that made the antidepressants work.

This work suggests that the development of new and better antidepressant medications should shift focus from trying to elevate levels of serotonin to working to strengthen excitatory connections. “The NARSAD Young Investigator Grant was the first grant I got in my scientific career, and also the first grant we got to support this project,” says Dr. Cai, the study’s first author. “The support from the Brain & Behavior Research Foundation greatly motivated and encouraged me and our research team to figure out the downstream signaling beyond the serotonin hypothesis of depression.”

Read the study announcement