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  • In a study that spanned 15 years, researchers at the University of Florida learned how a receptor called GPR158 functions in relation to depression.
  • In a study of mice that experienced suppression of GPR158, they were less likely to have stress-induced depression.
  • After the researchers came up with the structure of GPR158, they were then able to link it to the amino acid glycine.

Depression affects millions of people, and while numerous medications treat depression, it can be hard to find the right one.

While researching neurotransmitters, scientists at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology made a discovery that identified how an amino acid is connected to depression.

The discovery was based on more than a decade’s worth of research to learn more about how brain cell signaling works. While finding a link to depression was not the goal of the initial research, the scientists are excited about their findings since they could shape the future of depression treatments.

The findings are published in the journal Science.

According to the National Institute of Mental Health (NIMH), depression affects approximately 21 million adults in the United States per year. Depression rates rose dramatically during the COVID-19 pandemic and continue to be a problem, with rates increasing in children under the age of 18 as well.

While some people experience situational depression, which may come about because of circumstances (such as the death of a loved one), others experience depression for longer periods, and it can become Major Depressive Disorder.

Some signs and symptoms of depression the NIMH lists include:

  • feeling sad regularly
  • experiencing feelings of emptiness
  • having a decrease in energy or feeling fatigued
  • having trouble with sleep
  • feeling thoughts of self-harm

People who experience persistent depression symptoms may need treatment. Doctors may prescribe medications, suggest therapy, or recommend lifestyle changes to help depression symptoms.

Some depression medications include tricyclic antidepressants (such as imipramine or amitriptyline), selective serotonin reuptake inhibitors (such as sertraline or escitalopram), and serotonin-norepinephrine reuptake inhibitors (such as duloxetine or venlafaxine).

Since antidepressants can cause side effects, including thoughts of suicide, people taking them should check in regularly with their healthcare providers and keep them apprised of any such thoughts.

The authors did not initially set out to uncover a link to depression. Their goal at the start of their research 15 years ago was to research how brain cell receptors work.

“Fifteen years ago we discovered a binding partner for proteins we were interested in, which led us to this new receptor,” said Prof. Kirill Martemyanov, one of the study authors. “We’ve been unspooling this for all this time.”

Prof. Martemyanov is a professor at the Department of Neuroscience at the University of Florida Health.

During the time that followed, the researchers discovered a receptor called GPR158. They learned through studies with mice that if a mouse experienced suppression of that receptor, then it would be more resilient to stress-induced depression.

“Genetic suppression of GPR158 in mice results in a prominent antidepressant phenotype and stress resiliency, making GPR158 an attractive target for development of new antidepressants,” write the authors.

Next, the authors wanted to answer the question of where this signal was coming from. They were able to answer this in a 2021 study when they determined the structure of GPR158.

Learning about the structure of GPR158 was a game-changer for the researchers.

“We were barking up the completely wrong tree before we saw the structure. We said, ‘Wow, that’s an amino acid receptor. There are only 20, so we screened them right away and only one fit perfectly … it was glycine.”

– Prof. Martemyanov.

Glycine is “a most important and simple, nonessential amino acid in humans, animals, and many mammals” according to a 2017 review of research.

After discovering that glycine was sending the signal and that GPR158 binds to glycine, the scientists were surprised to learn that it was an inhibitor and renamed it mGlyR (metabotropic glycine receptor).

The discovery of mGlyR should open the doors to new research involving depression treatment, which Prof. Martemyanov plans to explore.

Dr. Simon Faynboym, a doctor who has worked with the American Psychiatric Association, discussed the study with Medical News Today.

“The study basically shows that glycine can interact with the GPR158 system,” said Dr. Faynboym. “There is a biochemical pathway the researchers prove, but more importantly the takeaway is that this pathway could be the possible connection as to why glycine and taurine can possibly have antidepressant properties.”

Dr. Faynboym is currently a delegate to the California Medical Association.

While Dr. Faynboym noted the importance of the research, he did point out that depression is “highly complex” and said that more than one neurotransmitter is involved.

“There are many factors that take place when dealing with depression,” commented Dr. Faynboym. “Depression involves multiple neural networks, different neurotransmitters leaving and coming into neurons at different speeds, and involves all parts of the brain. Mental health is one of the most complex medical specialties due to the dynamics of the brain.”

With that in mind, Dr. Faynboym highlighted the importance of this type of research. “This is why research articles like this one push the field of psychiatry further along, as it gives us another peak behind the curtain of the great unknown, which is the brain.”

Dr. Jessica Turner, a psychiatrist based in Palm Beach Gardens, Florida, also spoke with MNT about the study findings.

“This paper proposes targeting a specific receptor in the brain in an area that is well known to have associations with depression, the medial prefrontal cortex,” Dr. Turner said. “The hope is that with more targeted treatments in the future, we can find better, more effective relief for people experiencing depression.

While Dr. Turner calls the findings “an exciting new development,” she did point out that more research is needed.

“First scientists would need to find a way to target the glycine specifically towards the mGlyR receptors in the brain,” said Dr. Turner.