Depression: An amino acid may be key to improving treatment

The discovery was based on more than a decade's worth of research.

ISLAMABAD, (Online) - 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.

Depression: Things to know

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.

Brain cell receptors and depression

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. An amino acid may be key to treating depression

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.