Genetic link to depression.

Scientists discover two gene variations linked to the condition Depression which can run in families and be in the genes. While it has long been known that the condition can run in families, researchers have struggled to find any DNA mutations linked to it, despite analyzing more than 9,000 cases. This had led to debate over whether people inherited a susceptibility to the illness or if another factor, such as the environment was the true culprit. Studies on severe depression within families have shown some individuals can be up to three times more likely to develop it if a parent or sibling has suffered. Psychiatrists have identified two gene variants that are associated with major depressive disorder (MDD). This is a particularly severe and recurrent form of the condition, also known as clinical depression, which strikes up to 10 per cent of people at some point in their lives.

According to the World Health Organisation, clinical depression carries the second heaviest burden of disability among all medical conditions worldwide. Researchers believe the findings could lead to new drugs for the complex disorder. The study, published in Nature, was conducted by Professor Jonathan Flint, of Oxford University, and his colleagues at the Virginia Commonwealth University in the USA and researchers throughout China. The researchers managed to pinpoint two gene mutations behind the condition by analyzing the complete DNA of over 10,500 Chinese women, about half with MDD and the others acting as controls.

Jonathan Flint in his project, an effort to find genetic sequences linked to depression, showed the first hint of success 18 months ago. His team reported the first two genetic markers reproducibly linked to major depressive disorder, one of the leading causes of disability globally. The findings could guide biologists to new drugs, and could one day be used to aid diagnosis. Many in the field are excited that the markers have been unearthed. The results look set to end years of debate over whether sequences for such a complex disorder could be found and Flint’s study may serve as a framework for future attempts to collect data from tens of thousands of people. More than 350 million people have depression. The disorder’s symptoms and severity can vary widely from one person to the next, and particularly between men and women. This suggests that different conditions have been lumped together into one diagnosis, complicating genetic analyses.

By early 2014, Flint, Kendler and a team of collaborators had analyzed DNA sequences from 5,303 Chinese women with depression, and another 5,337 controls. As Flint expected, 85% of the depressed women had a severe form of the disorder called melancholia, which robs people of the ability to feel joy. “You can be a doting grandparent and your favorite grandchildren can show up at your door,” says Douglas Levinson, a psychiatrist at Stanford University in California, “and you can’t feel anything.”The analysis yielded two genetic sequences that seemed to be linked to depression, one in a stretch of DNA that codes for an enzyme whose function is not fully understood, and the other next to the gene SIRT1, which is important for energy-producing cell structures called mitochondria. The correlations were confirmed in another set of more than 3,000 depressed men and women and over 3,000 controls.

The mitochondrial connection chimes with previous work, including some from Flint’s lab3, that has linked mitochondrial abnormalities to depression. “It’s an appealing bit of biology for a disorder that makes people tired and unmotivated,” says Levinson. But he is most intrigued by the way Flint and his colleagues designed their study. Levinson says that the Psychiatric Genomics Consortium, of which he is a member, has analyzed data from 17,000 people with depression without finding a genetic hit, as Flint had heard. In light of Flint’s results, the group, which is made up of researchers who agree to pool genetic data, is now investigating whether limiting the analysis to people with particularly severe depression might change things.

If it does, still more samples will be needed before other genetic links emerge. Levinson expects a series of biobanking efforts in places including the United Kingdom, the Netherlands and Australia to provide tens of thousands of genomes for analysis within the next five years. The hope is that as more genetic links are found, they will flag up groups of proteins known to work together to affect certain cellular functions: these ‘pathways’ could be investigated as drug targets, and for their potential to make diagnosis of depression more definitive.

Flint’s success may energize that search, says Patrick Sullivan, a psychiatric geneticist at the University of North Carolina at Chapel Hill.

 

For more information please visit: www.vcu.edu

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