For the first time, scientists have identified two genetic variants that make a person more likely to experience major depressive disorder. While the discovery is isolated to a subset of 5,303 Han Chinese women, it's hoped it will point researchers in the direction of better treatments and diagnosis for depression in the future, and emphasises the fact that depression is a disease, not just a mental state, and one that certain people can be predisposed to from birth.
"We are at the beginning of a trail that can lead us to clarifying the underlying biology of depression, which can then open up treatment possibilities that have hitherto been impossible," one of the researchers, Kenneth Kendler, a psychiatrist and human geneticist at the Virginia Commonwealth University in the US, told Arielle Duhaime-Ross at The Verge.
The discovery is exciting not just because it could transform our understanding of the disease, but because experts working in the field weren't even sure these genetic markers existed in the first place. According to Heidi Ledford at Nature Magazine, a previous study of 9,000 people with major depressive disorder turned up nothing, as did a separate analysis of 17,000 people.
But now we know for sure they're there, in Han Chinese women, at least, who were chosen in order reduce the variability of the results. The researchers selected 5,303 Han Chinese women with depression, and an additional 5,337 controls. In the group with depression, the team found that two genetic variants - both on genes located on chromosome 10 - appeared to be linked to depression.
While one of these variants is located on a piece of DNA that codes for an enzyme that we don't yet understand, the other sits right next to the gene SIRT1, says Ledford, which plays a role in the workings of mitochondria - the energy powerhouses of cells. Perhaps this particular variant is having an effect on the proficiency of a person's mitochondria, one of the team, Douglas Levinson from Stanford University in the US, suggested. "It's an appealing bit of biology for a disorder that makes people tired and unmotivated."
The team's analysis was repeated on a further 3,000 Han Chinese women with depression and over 3,000 controls, they found the same correlation. The results have been published in Nature.
Interestingly, when the team tried to repeat the analysis in a large subset of Europeans with severe depression, no correlation between the disease and this genetic variant was found. Kendler told The Verge that this could be because "part of the genome that 'hosts' these variants differs substantially in European versus East Asian populations".
While scientists debate over the significance of the find, the team remains hopeful that with further analysis using huge datasets of people with severe depression from around the world, more genetic links can be identified, now that we know that they're there. And if they can find these, they might be able to link them to malfunctioning proteins that can be targetted by new drug treatments.
"Right now, all of the commonly used antidepressants are based on biological hypotheses that are more than 50 years old," Harvard psychiatrist, Jordan Smoller, who was not involved in the research, told The Verge. "By opening a window onto specific genes related to the development of depression, genetic research may reveal new biological pathways that can lead to more effective and targeted treatment options."