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Blood speaks louder than words in depression diagnosis

A patient undergoes an optical topography exam for depression. The system measures changes in blood flow within the brain.

TOKYO -- The man in his mid-20s was working six days a week. He was so busy that he ended up skipping meals. Yet even with his nonstop pace, he was struggling to handle his responsibilities. His boss believed he had depression and urged him to visit a psychiatric clinic in Tokyo run by Dr. Noriyuki Kawamura.

     The diagnosis, it seemed, would be a formality. Except Kawamura found the man was not suffering from depression at all -- he was dehydrated. By eating better, drinking more water and following the doctor's other lifestyle guidelines, he recovered.

     "If that man had visited a regular psychiatric clinic," Kawamura said, "it is certain he would have been diagnosed with depression and treated with antidepressants."

     Approximately 1 million people in Japan are clinically depressed. Until recently, doctors could rely only on subjective observations to diagnose the condition and gauge its severity. But new techniques allow for measuring depression numerically. This is how Kawamura spotted his patient's real problem.

     The doctor performed a blood test for a compound called ethanolamine phosphate, or EAP. The test showed the man's EAP levels were normal, and as far as Kawamura was concerned, that was enough to rule out depression.

     EAP is a biomarker Kawamura is developing in collaboration with Human Metabolome Technologies, or HMT, a company that emerged from Keio University. The bioventure specializes in analysis of cellular metabolites.

Early detection

Typically, when depression is suspected, mental health professionals interview the patient. Conclusions are based on codes in a book called "Diagnostic and Statistical Manual of Mental Disorders." But patients are not always completely open about how they feel, and without any way to collect objective data, it is difficult for doctors to make the right call.

     Kawamura began studying EAP as a biomarker for depression in 2002, when he was working at Japan's National Center of Neurology and Psychiatry. "When a person begins experiencing psychiatric symptoms they also suffer a decline in immunity," the doctor said. "I figured there must be something that would show up in their blood."

     Kawamura sought HMT's help to pinpoint and analyze the biomarker. In studying metabolites, the company normally uses a technique known as capillary electrophoresis, which is difficult to do on a large scale. It costs around 400,000 yen ($3,911) per sample.

Zeroing in

To create a less expensive test for EAP, the company developed a new method based on a combination of chromatography and enzymes. This costs only 10,000 yen to 20,000 yen a sample. According to HMT, the EAP blood test can detect depression with better than 80% reliability; it can rule out depression with accuracy of greater than 95%.

     Kawamura seems confident in the test, having run it about 2,500 times on some 1,200 patients.
     Many people are still reluctant to go in for psychiatric evaluation. But a simple blood test that indicates depression would accomplish two things: It would allow even physicians to make early diagnoses, and it would help in convincing patients that seeing a psychiatrist is the best path.

     HMT plans to increase the number of clinics that use the EAP test on a trial basis, starting in the current fiscal year through next March. The company hopes to get the test covered by Japan's health insurance system by 2019.

     "EAP," Kawamura said, "will change the way depression is diagnosed and treated."

     EAP is not the only new method that promises to take the guesswork out of diagnosing depression. Optical topography, an imaging technique based on near-infrared spectroscopy, is another.

     A sensor-studded helmet is fitted over the patient's head. The subject is then asked to recite words that begin with "a" for a set amount of time. As the patient does this, beams of near-infrared light are directed onto the scalp to measure changes in blood flow inside the brain.

     Optical topography can reportedly distinguish between various mental disorders, including depression and schizophrenia. A total of 26 university hospitals and other medical facilities in Japan are using the technique. Since it is covered by the national health insurance system, the procedure looks likely to spread.

     Kiyoto Kasai, a professor in the Department of Neuropsychiatry at the University of Tokyo, stresses the importance of diagnosing precisely the right mental condition.

     "The medications used to treat depression should not be administered to people with schizophrenia or bipolar disorder, and the nonmedical treatments also differ," Kasai said. "So the advent of optical topography is hugely significant."

     Kasai cited a number of cases in which optical topography revealed signs of schizophrenia in patients who were thought to have depression but were not responding to antidepressants.

     "If schizophrenia is not suspected, the doctor can fail to glean relevant information from the patient," Kasai noted.

Scope of the problem

The World Health Organization calls depression a growing global burden and estimates that more than 350 million people suffer from it.

     In Japan alone, Ministry of Health, Labor and Welfare statistics show there were 958,000 diagnosed cases of clinical depression in 2011. That compares to 433,000 cases in 1996, suggesting explosive growth.

     "Statistically, it looks like depression has been on the rise, but it would be hasty to conclude there has been an actual increase in the number of people with depression," cautioned Yutaka Ono, head of the National Center for Cognitive Behavior Therapy and Research and a board director at the Japanese Society of Mood Disorders.

    Ono noted that selective serotonin reuptake inhibitors, or SSRI drugs, were released in Japan in 1999. SSRIs are now a medication of choice for treating depression, and they have been heavily advertised since their debut. This has focused attention on the condition, resulting in more individuals seeking help.

     Nevertheless, Ono does believe depression is a growing problem in Japan, particularly in the corporate world.

     Ono said interpersonal bonds between workers have weakened, even in rural areas. "And companies are less willing to shoulder the burden of redundant staff. It seems depression can be linked to increased competition among employees inside companies," he suggested.

     Japan's parliament is now discussing an amendment to the industrial safety and health act that would require employers to pay more attention to mental well-being. The new diagnostic tools may help ensure workers get the treatment they need.

Nikkei staff writers Motoki Sasaki, Takashi Kimura and Natsuko Katsuki contributed to this report.


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