Depression is the most common mental illness there is. The WHO estimates that 264 million people around the world are affected. In the US the National Institute of Mental Health (NIMH) estimates that 16.2 million U.S. adults had at least one bout of depression in 2016. Although it has long been known that this disease is not limited to psychological aspects and can affect families, the genetic variations associated with it are still unknown to science. A study published in the scientific journal Neuron has identified a specific gene that is essential for mood regulation and could explain why depression affects more women than men. In fact, women are twice as likely to be affected as men. Since one in five patients does not respond to antidepressants, these results may 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, while the rest is due to environmental factors, especially stress. Epigenetic factors include long non-coding RNA genes. These are biological processes that lead to changes in gene expression that are not caused by changes in the genes themselves. To assess the contribution of these genes to depression, researchers at Mount Sinai in New York have studied thousands of candidate molecules. Using bioinformatics, they were able to restrict their field of research to the LINC00473 gene.
They then expressed it in the neurons of adult rats and found that this gene induces a resistance to stress only in females, which changes in female depression. This was also associated with changes in synaptic function and gene expression. LINC00473 is deregulated in the female cerebral cortex, which may explain why women are more susceptible to depression, researchers say.
“A very promising roadmap to move forward”.
“Our study provides evidence of an important new family of molecular targets that could help scientists better understand the complex mechanisms that lead to depression, especially in women,” says Orna Issler, the study’s lead author. These findings on the biological basis of depression can lead to the development of more effective drug therapies to combat a disease that is the leading cause of disability worldwide. Although researchers are mainly focusing on LINC00473, they are also investigating other genes that are considered good candidates.
“Our work suggests that the complex brain of primates, in particular, uses long, non-coding RNA to regulate higher brain functions, including mood and that an interruption of these processes can specifically contribute to diseases such as depression and anxiety,” continued Dr. Issler.
Our study paves the way for a whole new class of molecular targets that could help explain the mechanisms that control susceptibility and resistance to depression, particularly in women,” said the corresponding author Eric J. Nestler. Long, non-coding RNA can lead us to better and more effective ways of treating depression and, equally importantly, to diagnose this debilitating disease. There is still a lot to do, but we have a promising roadmap to follow,” he said.
Treating depression differently according to the patient’s gender
By March 2018, a Canadian study had already identified genetic mechanisms that contribute in different ways to depression in men and women.
By measuring the intensity of gene expression in the brain of people who died while depressed, researchers found that genes that affect synaptic function are most strongly expressed in women’s brains. In contrast, genes influencing immune function have been found to be more strongly activated in men.
“This study document highlights the different molecular mechanisms that contribute to depression in men and women,” the scientists welcomed and called for different treatment of patients suffering from depression according to gender.