Oct 22, 2015 11:54 AM

Spy Claims Fade as Chinese Decipher Depression

A researcher at the Beijing Genomics Institute in Shenzhen analyzes samples as part of a study on depression patients on July 1
A researcher at the Beijing Genomics Institute in Shenzhen analyzes samples as part of a study on depression patients on July 1

(Beijing) – Eight years ago, suspicious health officials apparently fearing a foreign espionage plot prevented Chinese psychiatrists from collaborating with U.S. and British counterparts on a major study of depression.

Those suspicions, possibly originating at a high-level government agency, forced some psychiatrists and hospitals to drop out of the medical study launched by researchers from America's Virginia Commonwealth University (VCU) and Britain's Oxford University.

Oxford's Dr. Jonathan Flint, who led the research with VCU's Dr. Kenneth Kendler, said that at one point during the lengthy study so many Chinese hospitals dropped out that the project had to be temporarily suspended.

But Flint and Kendler persisted in their search for collaborators until eventually finding enough cooperative – even courageous – psychiatrists in Shanghai, Shenyang and other cities to complete the project this year.

Now their efforts are paying off, as the international medical community has recognized the project known as CONVERGE – short for China Oxford and VCU Experimental Research on Genetic Epidemiology – as a major milestone in the fight against depression.

The project's survey of 12,000 Chinese women from the nation's Han ethnic group, half of whom suffered from depression, helped researchers identify two gene sequences linked to the disease afflicting hundreds of million of people around the world. The findings were published in July in the journal Science.

Collaborating with researchers in China was a key to the project's success because Han people – who comprise about 95 percent of the country's population – share among themselves certain genetic structures and mutations. Chinese hospitals and psychiatrists thus afforded CONVERGE researchers access to a valuable genetic pool that would have been difficult to find in an ethnically diverse country such as the United States.

"China has been the key to our research," said Flint, who worked with hundreds of researchers at 59 hospitals across the country.

China was also prime research territory because many of the tens of millions of Chinese who suffer from depression are forced to live with the condition. Experts say many go untreated due to a lack of medical resources or because they choose to avoid the social stigma attached to being diagnosed with depression. Those who accept treatment are also likely to seek care at a major hospital.

According to the most recent statistics available, which were published in 2009 by the medical journal Lancet, about 90 million people in China live with depression. Flint said women in the country are more susceptible to depression than men.

The World Health Organization (WHO) estimates 11 percent of the planet's population suffers from some degree of depression, and 350 million need clinical help. The disease has also been linked to most of the 800,000 suicides reported worldwide each year, the WHO said.

Dr. Zhang Zhen, a psychiatrist at Zhenjiang Mental Health Center in the eastern province of Jiangsu, said depressed people in rural parts of China are particularly notorious for refusing treatment.

"Many patients try committing suicide by slicing their wrists before being rushed to a hospital where they're diagnosed with depression," Zhang said.

Critical Links

Flint said one gene sequence that CONVERGE researchers identified as linked to depression is an enzyme whose function is still not clear. Another sequence is closely tied to dysfunctional mitochondria, which are tiny powerhouses inside cells that produce energy.

These findings may explain in part why depressed people often suffer from fatigue or lack interest in everyday activities, Flint said.

The study's results do not point to a clinical solution to depression, Flint said, but could be conducive to future research into and help scientists develop new anti-depressant drugs. The results also may help doctors more accurately diagnose the disease, he said.

Previous studies had found that depressed people may have abnormal levels of certain substances such as neurotransmitter, a sense messenger molecule in their brains. Moreover, clinical studies of twins have suggested depression may be hereditary.

CONVERGE researchers were apparently the first to uncover a possible link between depression and gene mutations – a link that scientists have long debated but previously could not prove or disprove since there are so many factors that can contribute to gene mutations.

The CONVERGE team succeeded because of their unique approach to probing the causes of depression, Stanford University's Dr. Douglas Levinson told Science. Levinson, a professor of psychiatry, has also studied depression, and thinks other scientists should look to the China study for inspiration.

One researcher not scared off by those 2007 espionage claims was Dr. Yang Fuzhong, chief psychiatrist at the Shanghai Mental Health Center. He was among the first to participate in CONVERGE in 2007.

Yang said finding candidates that met all of the research project's criteria was not easy. For example, each candidate had to be a woman between the age of 30 and 60 whose parents and grandparents were Han.

Psychiatrist Dr. He Qiang, a research collaborator at Shenjing Hospital in the northeastern city of Shenyang, said he counted it lucky to find just one viable candidate from among the 80 patients with depression visiting his clinic each day.

Interviewing patients was also challenging, He said. Each two-hour interview had to be conducted one-on-one and only with select patients. Questions touched on a patient's educational background, medical history and personal relationships. Some questions were sensitive. Then, the inside of each interviewee's mouth had to be swabbed for DNA sequencing tests.

"It was particularly difficult to talk it through with patients who were severely depressed, as they often failed to come up with the right words and logic," He said. "Or they simply strayed from the questions I asked."

More than 500 patients with depression undergoing treatment at Shanghai Mental Health Center and an equal number of healthy people were surveyed between 2007 and 2012, Yang said. Their stories varied, he said, and some were heart-wrenching.

For example, a married woman suffering from depression recounted during an interview with Yang how she had been sexually attacked as a child. "She was crying at the end of the interview," he said. "She had never told anyone, even psychiatrists she had seen, about her ordeal."

Complementary Research

Complementing the contributions of psychiatrists and hospitals was the private Beijing Genomics Institute, a non-profit research center in the southern city of Shenzhen. The institute's researchers did the DNA analysis that helped the CONVERGE team pinpoint the gene sequences linked to depression.

In exchange for their support, Chinese psychiatrists who participated in the research were trained to write science papers in English. That helped many see their work published in international journals; more than 25 research papers on depression written by CONVERGE collaborators in China have been published in the past three years.

"These papers have highlighted an important finding: Chinese patients are no different than patients elsewhere in terms of symptoms, how their (depression) develops, and in terms of the demographic features of patients," Flint said.

Studies by Chinese researchers have found that rates of postpartum depression are about the same among Chinese and Western mothers – a conclusion at odds with what many scientists have said about cultural and economic differences having a major bearing on mental disorders, Flint said.

But studies have also found that Chinese people with higher education levels are more prone to depression, Flint said, while in Europe and the United States it's the less-educated who are more likely to suffer.

Researchers say the benefits of CONVERGE and offshoot studies have buried any lingering suspicions about foreign spies disguised as psychiatrists – suspicions that almost scuttled the project.

He, the psychiatrist in Shenyang, said participating has helped him better understand depression in China. "As a researcher, I had an opportunity to gain access to the most advanced research practices in the world," he said, adding that the country's health officials have nothing to fear.

Back in 2007, Flint said, it wasn't easy to convince skeptical hospital officials to participate in the depression study. So he learned the Chinese ways of building relationships by "networking, wining and dining a lot," he said.

"We ended up spending a lot of time trying to change people's mindset, to make them believe this is simply international research, and to stress the importance of cooperation between China and other countries," he said.

And more collaboration is on the horizon: The CONVERGE team and Peking University recently agreed to work together on the next phase of research that will sample 15,000 people with depression. Researchers will be looking for more links between gene sequences and the disease.

(Rewritten by Li Rongde)

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