Deep low over China: seeking the causes of depression

Whether you live in affluence in one of the world's leading economies, or in poverty in a developing country with few resources, depression is likely to be one of the top three causes of ill health among your compatriots. It is often correlated with stressful events such as emotional abuse in childhood, or bereavement; it correlates with both fear and anxiety. But not everyone who experiences such stresses becomes depressed, and there is good evidence that some are genetically more susceptible than others.

Jonathan Flint, Professor of Molecular Psychiatry, is dedicated to tracking down those genetic variants that predispose us to become depressed. However, with such a heterogeneous condition, you need a very large sample to distinguish genetic from environmental effects, and until recently that had not been available. Professor Flint, of the Oxford's Wellcome Trust Centre for Human Genetics, took advice from his colleagues in the Clinical Trial Service Unit and went to China to conduct the world's first truly large-scale study of depression, funded by the Wellcome Trust.

'It's a common disorder', he says, 'but you want the sample to be as homogeneous as possible.' Designing the study in partnership with Professor Ken Kendler of Virginia Commonwealth University in the US, he trained dozens of doctors to carry out standard two-hour assessments. These doctors then recruited 6,000 Han Chinese women being treated in 50 psychiatric hospitals across 30 cities in China. Each woman also gave a DNA sample. For comparison, he collected the same information from women without depression visiting GPs or gynaecology wards.

The study has already produced a series of papers, co-authored with the Chinese psychiatrists, that outline the risk factors and clinical features of depression in China. Many of the women studied lived through the Cultural Revolution, but – perhaps surprisingly – the researchers found no difference in rates of depression between those who did and didn’t, once other factors were controlled for. And while in most respects depression in China does not differ from depression anywhere else, one interesting difference emerged: Chinese women who describe their parents as 'controlling' are less likely to be depressed, while in Britain and the US the effect is reversed.

On the key question of depression's biological basis, the jury is still out. While the study found many common variants that were associated with the condition, their combined effect was very small. 'We need to look for rarer genetic differences, those that turn up in fewer than 1 in 100 people', says Professor Flint. To do that requires sequencing whole genomes, a much more expensive task than searching for known variants. Already this has begun, with 100 genomes sequenced in January 2012; completing the task will depend on funding.

The study also needs to be bigger. '6,000 is still not enough', says Professor Flint ruefully. Fortunately many of the hospitals in the study are still actively collecting data, now thoroughly engaged with the prospect of conducting research of truly international significance.