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Gene in brain's 'reward circuit' linked to depression

10 July 2017

By Cara Foley

Appeared in BioNews 908

A gene that could play a key role in depression has been identified.

While the gene, known as Slc6a15, was previously shown to be more commonly expressed in specific neurons in the brain, this is the first study to describe how the gene works in these cells. The neurons were situated in a region of the brain called the nucleus accumbens, which is part of the brain's 'reward circuit'.

'This study really shines a light on how levels of this gene in these neurons affects mood,' said Dr Mary Kay Lobo, an associate professor at the University of Maryland School of Medicine and senior author of the study. She theorises that people with low levels of Slc6a15 expression in the nuclear accumbens 'may have a much higher risk for depression and other emotional disorders related to stress'.

In the study published in the Journal of Neuroscience, mice were genetically modified to express low levels of Slc6a15. Following exposure to stress, these mice exhibited symptoms typically associated with depression. A second cohort was modified to express high levels of the gene. These mice displayed a 'resilient response to stress', according to Dr Lobo.

In addition, post-mortem analyses of the brains of people with major depression who had killed themselves, revealed a reduction in the level of Slc6a15 in the nucleus accumbens, indicating that relationship between the gene and the symptoms seen in mice extends to humans.

A primary symptom of depression is the inability to derive enjoyment from typically pleasurable activities. As doing something enjoyable normally activates neurons in the nucleus accumbens, this research could lead to the development of gene-targeted therapies for depression in this area of the brain.

Dr AJ Robison, a professor of physiology at Michigan State University and who was not involved in the work, told The Huffington Post: 'In order to improve, we really need to understand not only how the disease is happening and what went wrong to cause depression, but how the drugs work to combat it. This study should lead to a continuing body of work that can really make genuine progress in understanding how depression works and maybe even in treating it.'

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