There is an array of medications available to treat depression, but it is not clear why they work for some and not others. Scientists are also not sure why antidepressants are effective.
Scientists at the University of Maryland School of Medicine may have uncovered a piece of the puzzle, which could lead to new therapies for people with major depression that do not respond to the drugs already on the market.
The research team conducted a study to identify the primary role the S1c6a15 gene plays in either contributing to depression or protecting from stress, depending on how active it is in a part of the brain related to pleasure, reward seeking and motivation.
This is the first study to shed light on how the gene “works in a kind of neuron that plays a key role in depression,” according to the researchers at the University School of Medicine.
Even though the study utilized mice models, the research team analyzed donated brains from people who had committed suicide. Decreased levels of the gene’s activity were also found in those brains, as well.
The researchers hope that it is possible to develop drugs that are capable of encouraging the gene’s activities.
“I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interest in how it becomes dysfunctional in certain diseases like depression,” senior researcher Mary Kay Lobo said. “I hope that we can identify molecules that could potentially be therapeutically treated and targeted to treat depression.”
In 2006, Lobo and her colleagues discovered the gene was more common in certain neurons and later connected it to depression.
According to the Anxiety and Depression Association of America, nearly 15 million adults living in the United States experience major depression each year. That is about 6.7 percent of adults in the United States. Major depression can develop at any age, but is more prevalent in women.
Most medicines utilized to treat the condition were discovered by chance, said David Dietz, an associate professor at the State University of New Year. He said how the drugs work was not clear.
“We’re starting to really get an idea of what does the depressed brain look like,” Dietz said. “When you put the whole puzzle together, you see where the problem is. For too long we’ve been throwing things at individual pieces. It’s so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.”
It is still unclear how S1c6a15 works in the brain. However, it is believed that the gene transports three different types of amino acids into D2 neurons, a subset of neurons in the nucleus accumbens. The D2 neurons and nucleus accumbens play a role in pleasure, as they are activated when having sex, drinking alcohol and consuming delicious foods.
The amino acids are synthesized into neurotransmitters, which was previously linked to depression when there was an imbalance.
Even though the body may have abundant supply of amino acids, if the transporters are working improperly, the neurons in the brain may still not be getting the adequate amount.
“This gene is critical for putting very specific amino acids in the right place so neurotransmitters can be synthesized,” said an assistant professor at Michigan State University, A.J. Robison.
The study was published in the Journal of Neuroscience in July 2017.