Genetic link found for depression but 'cure' still a long way off

Scientists in two separate studies have established a genetic link to depression and have narrowed it down to a region of a specific chromosome (called 3p25-26).

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Depression is more than feeling a bit down; it can be a major and debilitating illness. Its clinical symptoms include low mood, pessimistic thinking, reduced energy and poor concentration, but if you ask a sufferer to describe it they will paint a more vivid picture than a list of symptoms can ever portray.

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Last Updated: 22 June, 2011 UAE

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The World Health Organisation estimates that around 121 million people are affected worldwide and it is among the leading causes of disability. According to Dr Yousef Abouallaban, medical director at the American Center for Psychiatry and Neurology in Abu Dhabi, it has become a very common phenomenon in the UAE.

The reasons why one person suffers from depression while another does not are many and varied, and it has long been believed that both genetic and environmental factors can be involved; 40 per cent of cases of depression are thought to be heritable, rising to 70 per cent in cases of recurrent and severe depression. For years, though, the genetic link to depression was not proven - previous studies claiming to link specific genes with depression were inconclusive - and it was not known where in our DNA the susceptibility to depression was located.

Now scientists in two separate studies, both published this month in the American Journal of Psychiatry, have established a genetic link to depression and have narrowed it down to a region of a specific chromosome (called 3p25-26).

The larger study, conducted by researchers from the Institute of Psychiatry at King's College, London, working with researchers from other centres in Europe and North America, examined DNA from 971 sibling pairs affected by severe and recurrent depression. The participants in the study provided a blood sample for DNA extraction and their DNA was assessed for genetic markers spread across the chromosomes. They found a clear genetic link to severe, recurrent depression in one area of chromosome 3.

At the same time, a separate and independent study of 100 families of heavy smokers with depression, carried out in the United States at Washington University, St Louis, also found a link with the same region of chromosome 3.

The results of the King's College study were a surprise even to the researchers. "I didn't expect that we would get a signal this strong," says Gerome Breen, lead author of the UK study and lecturer at the MRC Social, Genetic and Developmental Psychiatry Research Centre at King's College. "Usually in studies in depression we've got something that has been of marginal significance, if that, and this signal was quite strong."

Breen hopes that the studies may lead the way to further research that could improve the treatments available for patients with depression.

"This and other studies like it will gradually build up a picture of the biology of depression. Utilising the new technologies coming online in genetics means that we will be 'data-driven' - that we will systematically identify genes and their pathways and not have to rely on the accidental observations that have led to the few drug types on the market for depression."

Exciting though this breakthrough may be for the scientists, there is still a long way to go before gene-related treatment is available; it is thought that it will be 10 to 15 years before patients will see therapies based on genetic information.

According to Dr Michele Pergadia of the Department of Psychiatry at Washington University School of Medicine and lead author of the US study: "Our findings are not at the stage to inform treatment. There are many genes and environmental influences on depression, and these findings won't provide immediate benefit for people who are depressed. But this finding may be an important step toward understanding what may be happening at the genetic level contributing to depression."

Breen also emphasises that they have not found a "depressive gene".

"We haven't found specific genes as of yet. What we found is that this region of the chromosome almost certainly harbours genetic variations and mutations that increase risk for depression. It does show pretty clearly that there is a molecular basis for depression; that the basis of the disorder, at least in some of these families, is genetic or partly genetic."

There are other factors, too, that may limit the impact of the studies. First, they looked only at severe, recurrent depression; genetics are thought to play a lesser role in less severe and non-recurrent depression. Moreover, the studies involved only subjects of European ancestry, and although Breen says that it would "generalise across Europe at least", the results may not be so significant elsewhere in the world. According to Pergadia, "it is not possible to say at this time" how relevant the findings would be to, say, people of Middle Eastern origin.

Still more of a drawback is the issue of research funding. Despite the fact that depression is forecast to become the disorder with the highest disease burden in the world by 2020, rivalled only by heart disease in its impact as a public health problem, and that approximately one individual in six may experience a major depressive episode in his or her lifetime, it does not benefit from a proportionate amount of research.

"I don't think that depression has been prioritised in proportion to how common or severe it is," says Breen. "There's quite a lot more research gong on in comparatively rare cancers than there is in depression. There's also a lot more molecular and genetic research going on in disorders like schizophrenia and in dementia which are several times less common than depression."