Preemptive shock test

Hadassah has a simple new blood test that can easily identify potential post traumatic stress disorder sufferers.

Michal has had trouble sleeping since the terrorist attack. Every ambulance siren causes her to start, and every person wearing a large coat causes her to cross the street. Almost three years have passed since that day, but Michal still feels the shock as if it were yesterday. Her sister, Inbal, who was with her in the mall that day, also suffered from similar symptoms in the week following the bombing, but she has gradually recovered, and has been able to lead an ordinary life, barring occasional incidents. However, Michal seems to be stuck, as if her life came to a standstill on the day of the bombing.

Studies on post traumatic stress disorder (PTSD) indicate that metaphors such as "life stopped", "the brain is stuck at the moment of the incident", and "I can't get over it", are apparently more than mere expressions of events by some victims of trauma. This is apparently a mechanism that causes various types of stress hormones to affect the memory in way that reinforces it and makes it more sensitive. "It is known that all humans, and animals too, better remember information learned under situations of pressure and distress," says Prof. Arie Shalev, head of the Department of Psychiatry at Hebrew University - Hadassah Medical School.

If you think about it, this is a logical, and even critical, mechanism in evolutionary terms, but it apparently works all to well in cases of PTSD. Memories of the stressful event do not pass or blur over time; they remain present and strong, every hour of every day. One leading theory about PTSD assets that stress hormones operate in conjunction with hormones that delay change in the nervous system, resulting in memory becoming stuck, and unable to change.

PTSD victims are usually treated with both psychological methods and anti-memory drugs, but the treatment usually begins several months after the incident, when the disturbance starts affecting behavior. Could earlier treatment reduce some of the damage and save patients the severe affects of PTSD? Many researchers believe so.

"The problem in diagnosing PTSD is that the brain is an inaccessible organ to research," explains Shalev. "Differences can be seen between the brain of a person about to develop PTSD and the brain of a person about to recover, but the differences are small and indistinct. Nor is it possible to conduct MRI tests for everyone who comes into an emergency room. Our breakthrough would say, 'If this process affects the brain, we can certainly see evidence of it in the blood, which is much more accessible'."

Children also suffer

Shalev and his colleague, Ronen Segman of the Psychiatric Laboratory at Hadassah University Hospital-Mt. Scopus, turned to a fairly new technology, microRA, which can simultaneously examine tens of thousands of molecules in the blood. "This system can diagnose the presence of messenger RNA (mRNA) in the blood. These are proteins that genes manufacture to signal the body to do something. We can check and see what the bodies of different types of patient are about to do," says Shalev.

Lab work was done by Dr. Segman and Tanya Goltzer-Dubner. Prof. Nir Friedman and Noa Shefi from the Hebrew University’s Department of Computer Science did the computerized digitations of the data, and Prof. Naftali Kaminski from Sheba Hospital helped in the laboratory part of the research.

"Our study examined 24 people who suffered trauma and were diagnosed with shock upon arrival at hospital," says Shalev. "We found difference between their blood profile. Some patients had elevated levels of stress hormones - proteins that that block changes in the nervous system, and proteins that frequently found in the hippocampus, the area where we saw difference in MRI scans between patients who developed PTSD and those who recovered from shock.

"We hypothesized that the patients showing this blood profile were much more likely to develop PTSD. The test was able to correctly predict in ten out of eleven shock patients arriving at the emergency room whether they would show signs of PTSD four months later."

"Globes": What causes the difference between those who recover from shock and those who have trouble recovering?

Shalev: "A lot of factors cause the difference, none of which on its own can predict who will develop PTSD and who will not. Proximity to the traumatic event, prior events, psychological abandonment in childhood, a recovery environment from trauma, and biogenetic awareness are all factors investigated for which evidence has been found that they influence candidacy for PTSD. If we were to go gene by gene, we might find small differences in some genes between the group that are candidates for PTSD and the group that are not candidates. But you can get clear results with real predictive ability if you examine many molecules in the blood simultaneously."

How exactly do these hormones affect the brain to cause PTSD?

"The truth is that we don’t really know. We've hypothesized a mechanism, and I believe that by understanding the profile of proteins in the blood at the time of trauma, we can better understand the mechanisms. There are currently many theories that we might be able to support or disprove. I'm waiting for surprises."

"Patients would run away"

What are the practical applications of your test?

"The intention is to conduct a blood test on every shock patient, and those who have the candidacy profile will be monitored so we can initiate contact. We'll invite these persons for a few days of pharmaceutical and psychological treatments. We're already doing this at Hadassah Hospital. Before we began using this system, patients would simply slip between our fingers, and years might pass before they'd get treated."

Do your findings have commercial applications?

"That's definitely the idea. We've patented the test - not the simultaneous diagnosis of many proteins, which is a well-known method, but until now was only used to check a patient's tissue. We're the first to think by testing blood to diagnose brain injury. That's what we have patented. We now want to find a technology incubator where we can begin commercial development of the system.

"The Ministry of Defense knows of thousands of PTSD patients in Israel. Their medical treatment costs thousands of dollars a year, without even counting non-medical support they receive, such as disability or loss of work ability pensions. 12% of the people exposed to each traumatic event will develop PTSD symptoms - and that's a very conservative figure. This is a problem that costs health systems and economies of Israel and other countries a great deal.

"By contrast, the test cost us $600 during the research stage, and that the most it will ever cost. We hope to lower its cost to under $100 per patient."

Aren't you concerned that you might diagnose a person as a candidate for PTSD, thereby causing anxiety?

"No. We're talking about people who already know they're in distress. We don’t tell them, 'you're a candidate for a disease.' We just treat them sooner. What's the alternative? Not to treat them at all? In any case, these are matters that will have to be considered."

Published by Globes [online], Israel business news - www.globes.co.il - on February 7, 2005

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