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Depression Could be Genetic: slc6a15 Gene A Key Player

Depression Could be Genetic: slc6a15 Gene A Key Player

Written by Anjali Aryamvally, B.Tech (Genetic Engineering)
Article Reviewed by 
The Medindia Medical Review Team on July 8, 2017 at 2:39 PM
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  • Depression is a mood disorder which is characterized by a persistent feeling of sadness and lack of interest.
  • While genetics may be one of the underlying causes of depression, the exact genes involved are unknown.
  • The expression of Slc6a15 gene in neurons have been identified as playing a vital role in increasing or decreasing depression levels in both animals and humans.

A research team from University of Maryland was able to prove that the gene product of Slc6a15 is reduced in individuals with depression and increasing or up-regulating the Slc6a15 protein could mediate the risk of depression. While many studies have indicated Slc6a15 gene in depression, the current study focuses on the expression of this gene in the part of the brain called nucleus accumbens (NAc). The study is published in the Journal of Neuroscience.

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Depression Could be Genetic: slc6a15 Gene A Key Player

What is Depression?

While most of us might get depressed or feel sad several times during the course of a day, it can be called depression only if the feeling of sadness persists for a long period of time, which could mean several weeks or months. Depression affects the way an individual thinks, feels and behaves. Around 300 million people worldwide are affected with depression annually, a major part of them being young adults. A person or his or her family may identify depression if the following condition's persist:
  • Feeling of sadness and hopelessness
  • Loss of interest in activities that usually bring pleasure including food, hobbies and sex
  • Angry outbursts, frustration, anxiety, guilt or restlessness
  • Suicidal thoughts
  • Incapability of performing day to day activities including going to work, daily chores
  • Inability to concentrate and make decisions
  • Unexplained physical problems like shoulder or leg pain.
It is important to remember that depression is treatable with medication and psychotherapy. The important factor here is to identify whether one is indeed suffering from depression and needs to seek help.

Causes of Depression

There are a number of factors that could lead to depression. These could include:
  • Environmental factors like the place of stay and sedentary lifestyle.
  • Social factors like poverty, divorce, social awkwardness.
  • Intake of certain drugs which alter the neurotransmitters in the brain, or chronic pain as a result of diseases like cancer may also be a cause for depression.
  • Genetic factors are also indicated since individuals with a family history of depression are more susceptible. However, the underlying genes and its mechanism are not entirely known.

Role of Slc6a15 Gene in Depression

Previous studies had indicated that Slc6a15 gene is a risk factor for depression after research into the various parts of the brain including the hippocampus. The present study was conducted to reveal the role of the same gene in another part of the brain called the NAc in stress susceptibility which may lead to depression. It was observed that within the NAc, the Slc6a15 was concentrated in a subtype of neurons called D2. These neurons respond to a neurotransmitter called dopamine, which is a feel-good hormone that is transmitted when something invokes a happy feeling. This forms the basis for the reward system in the brain. You do something you like and dopamine is released, which makes you happy. In depression this reward system becomes non-functional.

In the study, mice were subjected to social stress and when the mice that exhibited withdrawal symptoms were examined, it was observed that the levels of Slc6a15 in the NAc were drastically reduced. However, when the researchers enhanced the gene levels in the neurons, the mice showed a resilient response to stress. Also, when the brains of individuals who had committed suicide were studied, they showed reduced proportion of NAc. This establishes that the mechanism extends from man to mice.

Concluding in the words of Mary Kay Lobo, senior author of the study, the finding "suggests that 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."

References :
  1. Chandra, R., Francis, T., Nam, H., Riggs, L., Engeln, M., Rudzinskas, S., Konkalmatt, P., Russo, S., Turecki, G., Iniguez, S. and Lobo, M. (2017). Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility. The Journal of Neuroscience, 37(27), pp.6527-6538.
  2. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility - (http://www.jneurosci.org/content/37/27/6527.full)
Source: Medindia

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