Thursday, April 14, 2005

A test for PTSD

Researchers at the Hebrew University Hadassah Medical School appear to have discovered a test that can predict who will have long term problems with PTSD.

The results of the first-ever findings, published in the prestigious journal Molecular Psychiatry, describe how the researchers looked for and discovered a physiological signature in peripheral blood cells of activities that mainly take place in the brain. Their research methodology was innovative in itself. They examined thousands of possible markers at once, using the best available technology at the time.

The researchers believe that after some improvement in the testing process, it will be possible to predict the PTSD symptoms. Hadasit, the Hadassah subsidiary in charge of promoting and commercializing intellectual properties generated at Hadassah, has already patented the findings of the research and is in advanced stages of developing a commercial diagnostic kit for PTSD.

“Now that we have found the signals, we are going to concentrate on detecting the genes, to shed more light on the biological processes in our bodies that cause mental diseases, and from this – to develop ways to prevent such diseases,” said Prof. Arie Shalev, head of Hadassah's Department of Psychiatry, who led the research with Dr. Ronen Segman of the Psychiatric Laboratory at Hadassah University Hospital-Mt. Scopus. 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
This is truly amazing. As some of you may know I have done a lot of work as an amateur on PTSD and its relationship to the use of unapproved drugs (you know, pot, heroin etc.) This work essentially confirms my finding that PTSD (of the long term variety) is a two factor problem. The two factors are genetics and trauma. The trauma can include combat, child abuse, living in a war zone and any other situation that is dangerous or life threatening (like living in a drug war zone) where the individual involved feels powerless to control the situation. For instance sky diving is life threatening but is not a situation where those involved have no control.

Globes online did an interview with Prof. Arie Shalev who lead the research team.
"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'."

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.
Professor Shalev goes on to say that the research he has done will provide a tool for further study of the mechanisms involved in PTSD.
"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."
There is more of the interview at Globes. Read the whole thing.

Canada Israel Comittee has also reported on Professor Shalev's work.
Emergency rooms are built specifically to take care of a patient's physical injuries. But what about emotional fallout due to the traumatic event that just took place - especially the delayed reaction of post-traumatic stress disorder (PTSD)?

Israeli researchers at the Hadassah University Medical Center in Jerusalem have determined that a simple blood test might enable psychiatrists to predict if a person will develop PTSD. The test can be conducted while they're still in the emergency room, only hours after the traumatic event occurred.

Post-traumatic stress disorder is a severe mental condition that can be severe, persistent and disabling, and occurs in a significant minority of trauma survivors beginning at the moment of the traumatic event, according to Prof. Arie Shalev, head of Hadassah's Department of Psychiatry.
Professor Shalev goes on to discuss how this breakthrough came about.
"The project was born from conversations between Dr. Segman and myself, following our previous work on the genetics of PTSD," said Shalev.

"We wondered how to improve the prediction and the understanding of this disorder from biological findings. We realized that current biological hypotheses did not yield much, and may take very long time to yield good-enough markers of PTSD - indeed of any other mental disorder. This is because any given contributing factor may only predict part of the total variance in the causation of a given disorder. Additionally, by going for one factor at a time, we might, in fact, miss the 'right' hypothesis altogether."

Using an innovative methodology, they simultaneously examined thousands of possible biomarkers using microarrays (gene chips). Microarrays, which have been used to measure the activity of thousands of genes at one time in cancer or immune cells, have given scientists "snapshots" of gene activity that lead to a better understanding of the cells and genetic machinery.

"Ronen suggested the use of micro arrays - where the team could test simultaneously thousands of hypothetical candidates - and look at gene expression in blood cells - as reflecting the central nervous system activity, at a timing that coincides with triggering and onset of the disorder," said Shalev.

"We further thought that since stress involves both the central nervous system and peripheral activation (such as higher blood pressure, higher levels of circulating hormones and change in immune factors) - the occurrence of post-traumatic stress disorder might indeed be biologically expressed in blood cells."
Professor Shalev talks about his breakthrough and what it means.
"Now that we have found the signals, we are going to concentrate on detecting the genes, to shed more light on the biological processes in our bodies that cause mental diseases, and from this - to develop ways to prevent such diseases," said Shalev.

He hopes the discovery will induce other researchers to investigate the connection between peripheral expression and central nervous system expression of a disease that affects the brain.

According to Shalev, the study has broken two boundaries.

"First, the idea that one must necessarily study the biology of the brain (which is impossible in humans). We suggest, instead, that one can productively study a 'signature' of central nervous system phenomena in the easily accessible peripheral blood cells," said Shalev.

"Second, we challenge the reluctance to conduct a study with generic - rather than specific hypotheses (generic = there will be a signature; specific = this gene should be expressed). In other words, we suggest, in this work that it is productive to start by throwing a wide net (the micro array - in which thousands of expressions are seen at the same time) - and than eventually go back to testing specific hypothesis on the basis of micro array findings."
Again there is more at the site. Read it.

Another site reporting on the research is The World Jewish Congress. The American magazine Psychology Today also has a report.

Deployment Link which deals with American military health issues is looking for veterans of either Operations Desert Shield or Desert Storm or Vietnam War to participate in a study of Post-Traumatic Stress Disorder, or PTSD. If you fit into one of those catagories contact them. The work is being done by Mount Sinai School of Medicine and the Bronx Veterans Affairs Medical Center in New York.

Here is an article by Prof. Shalev dealing with the genetics of PTSD. It was published in 2003.

The blog Crystal Clear which is written by a psychotherapist dealing with child psychology and family issues has also discussed the research.

And finally let me point you to some of my articles on the subject of PTSD and drug use.

Addiction or Self Medication?
Heroin
Genetic Discrimination
Cannabinoids - the Key to many Pains?
Big Mac - heroin attack
Capitalism, Pain and the War on Drugs
PTSD Pot Alcohol & Substance Abuse
The Problem with Drug Addicts
Fear of Marijuana

BTW thanks to the commenter SAO at Winds of Change and Joe Katzman also of Winds who brought this to my attention.

4 comments:

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THanks for the mention and link. I too am greatly interested and still have plans to blog more about this... Great post....job very well done

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eyesallaround said...

Interesting. I was in ICU for 2 months with a deadly strain of pneumonia, several surgeries, morphine hallucinations, and yet never experienced what I thought would be PTSD.. No flash-backs...