Depression: a gene could explain why women are more affected

Depression is the most common mental illness there is. Worldwide, 264 million people are affected, according to WHO estimates. In France, Public health France estimates that nearly 9 million people have experienced or will experience depression in their lifetime, i.e. one person in seven. If we have known for a long time that this disorder is not limited to psychological aspects alone and can affect families , the genetic variations involved are still unknown to science. Today, a study published in the journal Neuron highlighted a specific gene essential in mood regulation that could explain why depression affects women more. Indeed, the latter would be twice as much at risk as men. While one in five patients fail to respond to antidepressants, these findings could lead to more effective treatments.

In the past, studies have shown that about 35% of the risk of depression in both sexes is due to genetic factors, and the rest to environmental factors, mainly exposure to stress. The long non-coding ANR (RNAL) genes are part of the epigenetic factors. These are biological processes resulting in changes in gene expression that are not caused by changes in the genes themselves. Here, to assess the contribution of these genes to depression, researchers at Mount Sinai, New York (USA), screened thousands of candidate molecules. Thanks to bioinformatics, they were able to narrow their field of investigation to the LINC00473 gene.

They then expressed it in the neurons of adult mice and discovered that this gene induced stress resilience only in females, which is altered in female depression. This was also accompanied by changes in synaptic function and gene expression. In the cerebral cortex of women, LINC00473 is down-regulated, which could explain why women are more vulnerable to depression, the researchers suggest.

“A very promising roadmap for moving forward”

“Our study provides evidence for an important new family of molecular targets that could help scientists better understand the complex mechanisms that lead to depression, particularly in women.explains Orna Issler, lead author of the study. These discoveries about the biological basis of depression could aid in the development of more effective drug therapies to combat a disease that is the leading cause of disability worldwide.”. While the researchers are primarily focusing on LINC00473, they are also studying other genes considered good candidates.

“Our work suggests that the complex primate brain makes particular use of long non-coding RNAs to facilitate the regulation of higher brain functions, including mood. (…) and that dysfunction of these processes can contribute to pathologies like depression and anxiety in gender-specific ways”continues Dr. Issler.

“Our study paves the way for an entirely new class of molecular targets that could help explain the mechanisms governing susceptibility and resilience to depression, particularly in women. adds corresponding author Eric J. Nestler. Long non-coding RNAs could guide us to better and more effective ways to treat depression and, just as importantly, to diagnose this debilitating condition. There is still a lot of work to do, but we have provided a very promising roadmap moving forward”he enthuses.

Treating depression differently depending on the patient’s gender

In March 2018, a canadian study had already shed light on genetic mechanisms contributing to depression in different ways depending on the sex.

By measuring the intensity of gene expression in the brains of people who died while depressed, the researchers found that genes affecting synaptic function were expressed more strongly in the brains of women. On the contrary, the genes affecting the immune function would activate more vividly in men.

“This document study highlights the divergent molecular mechanisms that contribute to depression in men and women”welcomed the scientists, therefore calling for different treatment of patients suffering from depression according to their sex.