In a new study, researchers found that a group of proteins called 4E-BPs, involved in memory formation, is the key to unlocking the antidepressant effect of ketamine in the brain.
The discovery could lead to better and safer treatments for certain patients suffering from major depression.
The research was conducted by a team from McGill University, Université de Montréal, and Carleton University.
Because more than 30% of patients are resistant to selective serotonin reuptake inhibitors (SSRI), the most commonly-prescribed antidepressants, finding an effective treatment for major depressive disorder is challenging.
Initially, ketamine was approved for anesthesia and pain relief.
Since its discovery, researchers have been studying new uses for this drug, and ketamine was approved last year for patients with major depression who are treatment-resistant.
Unlike standard antidepressants, which can take several weeks to have an effect, ketamine works within hours.
Until now, little was known about the molecular mechanism that triggers the antidepressant effect of ketamine on the brain.
In the study, researchers examined the effect of ketamine on behavior and neuronal activity.
Using genetic tools to remove proteins from specific brain cells, the team found that when 4E-BPs are absent in the brain, specifically in neurons, ketamine cannot produce its antidepressant effect.
4E-BPs act as a switch to turn on or off the process of protein synthesis—an essential component of memory formation.
The discovery and approval of ketamine for treatment-resistant patients were considered a major advance in modern psychiatry.
Despite its promise, ketamine remains a less-than-perfect therapy because it can be addictive.
The researchers hope that their findings will pave the way for better and safer antidepressant therapies for patients with major depressive disorder.
In the next steps, the researchers will examine whether males and females have different responses to ketamine.
This could have important implications for treatment for people with depressive disorders, among which women are strongly overrepresented.
One author of the study is Nahum Sonenberg, a professor at the Department of Biochemistry at McGill University.
The study is published in Nature.
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