By David Cyranoski of Nature magazine
The largest-ever study of the genetics of depression is set to go ahead in China, after a major survey found that the condition largely has the same triggers and symptoms there as in the West -- albeit with a few startling exceptions.
Previous studies on twins in Sweden have shown that genetics explains about 40% of a woman's risk of depression, and about 30% of a man's. Finding the genes responsible may help to make treatments more targeted and thus more effective, but identifying those genes has proved exceedingly difficult. The sheer diversity of symptoms involved in depression can make it difficult to be sure that patients actually have the same underlying disorder, and any genetic contribution is likely to come from many genes, each having a small effect.
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"It was clear that we needed a very large sample, [one that was] ethically homogenous, and to do it cheaply," says molecular geneticist Jonathan Flint at the University of Oxford, UK. Flint is one of the leaders on the CONVERGE consortium, a collaboration between Oxford, the Virginia Commonwealth University in Richmond and 53 provincial mental-health centres in China. "The only place that fitted was China. Where else could we access that many people and have sufficient control over quality?" asks Flint.
The consortium, which began in 2008 with a £1.5-million (US$2.5-million) grant from UK charitable funder the Wellcome Trust, chose to study only women, who are known to have a two-fold higher risk of depression across the globe than men. They also selected only patients whose four grandparents were all Han Chinese; and only those with recurrent depression, an indicator of a likely genetic component.
The first data from almost 4,000 subjects were published in the Journal of Affective Disorders last week, with ten more papers to follow over the next few months, and the survey is revealing some surprises. A higher level of education is associated with a greater risk of depression in China, for example -- the reverse of the relationship in Europe and the United States.
This chimes with the latest results from the World Health Organization's World Mental Health Survey Initiative, published last week, which found that those with the lowest level of education in China and Japan had only one-fifth the likelihood of developing depression as those with the highest education levels. In other countries, a lower education level was linked to a similar or higher risk of depression than the most educated.
And whereas having authoritarian parents seems to increase the risk of major depression in the West, CONVERGE found that having an overprotective father actually reduces the risk of depression in Chinese women.
Overall, however, the Chinese cases of depression seem to follow Western patterns of risk factors and symptoms. Stressful life events, childhood sexual abuse and authoritarian parents increase the risk with about the same dose-response relationship. Earlier onset of depression makes patients less likely to marry, more likely to suffer anxiety and more likely to be chronically depressed. "Depression is the same. The nature of the illness is the same," says Flint.
The CONVERGE team has already collected DNA samples from their subjects, and will use them to carry out genome-wide association studies to look for variations in genes shared by the disease group. The method has become a powerful tool for investigating some diseases, but has yet to prove itself in psychiatric disorders5. The consortium now plans to increase the study group to 6,000 patients and 6,000 controls over the next two years, and will submit a grant application to the Wellcome Trust to boost this to 30,000 patients.
Shenxun Shi, a psychiatrist at Huashan Hospital at Fudan University in Shanghai, and one of the leaders of CONVERGE, says that the preliminary studies could also have a more immediate impact: discouraging authoritarian parents from hitting their children. "Most parents in China don't think of bodily punishment as child abuse," he says. "Our study shows that physical punishment may be a risk factor for depression. That result could open public discussion and prevent depression."
This article is reproduced with permission from the magazine Nature. The article was first published on August 1, 2011.
