Researchers have taken an in-depth look at the function of a gene that may be linked to the development of major depression. Their findings show that its activity levels might determine our susceptibility to stress and negative stimuli.

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New research has found that individuals prone to depression have a low activity level of the Slc6a15 gene.

According to the National Institutes of Mental Health, major depression is a leading cause of disability among adults in the United States. Almost 7 percent of U.S. adults experienced episodes of depression in 2015, and the World Health Organization (WHO) indicate that around 800,000 suicides take place worldwide each year.

Depression can affect the way a person performs even the most basic daily activities, and it can severely impact productivity and general well-being.

Mary Kay Lobo, Ph.D., alongside other researchers from the University of Maryland School of Medicine in Baltimore, conducted a study focusing on a gene known as Slc6a15. This gene has been thought to play an important role in the onset of depression.

Dr. Lobo and colleagues set out to uncover the specifics of how this gene's activity levels might affect mood swings. Their study was published recently in the Journal of Neuroscience.

Low gene expression in over-stressed mice

In a previous study published in Nature Neuroscience, Dr. Lobo and collaborators had concluded that the Slc6a15 gene was most commonly found in a type of neuron located in the nucleus accumbens, which is a region of the brain largely responsible for the brain's reward circuit.

The neurons found in the nucleus accumbens dictate whether, and to what extent, we feel pleasure when we perform normally satisfying activities, such as eating, drinking, or spending time with friends.

The nucleus accumbens works with two main neurotransmitters, or chemical messengers, called serotonin and dopamine. These regulate our happiness levels and how well we handle stress.

Dr. Lobo and her colleagues studied D2 neurons, a set of neurons in the nucleus accumbens that are sensitive to dopamine. They started their research by monitoring male mice susceptible to depression, focusing on the importance of the Slc6a15 gene in D2 neurons in adjusting the specimen's response to intense stress.

The researchers found that mice that did not naturally respond well to stress had significantly lower Slc6a15 gene activity levels in their D2 neurons when introduced to critical situations.

To understand the impact of less active Slc6a15 genes versus highly active ones, the scientists also monitored mice whose Slc6a15 gene activity levels had been artificially brought down. It was observed that these mice also failed to respond well when exposed to stressful situations.

Higher gene activity improves resilience

Finally, the researchers studied mice whose Slc6a15 gene activity levels had been intensified. These mice, by contrast, responded well when faced with stress factors.

Then, in order to test for Slc6a15 gene expression, the team examined the brains of people who had experienced major depression or committed suicide.

They obtained similar results for humans susceptible to depression: the activity levels of the Slc6a15 gene in D2 neurons were significantly reduced in people who had little stress resilience.

The findings suggest that the answer to depression may lie in how active the Slc6a15 gene is, and that artificially enhancing its expression in the D2 neurons may improve the way in which stress is handled.

"[...] people with altered levels of this gene in certain brain regions may have a much higher risk for depression and other emotional disorders related to stress," says Dr. Lobo.

Despite their detailed study, the scientists are still unsure of how the Slc6a15 gene functions. They surmise that the gene's activity levels may affect the balance of neurotransmitters such as dopamine, but further research will be necessary to confirm this theory.

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