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, who led the research with Dr. Ronen Segman of the Psychiatric Laboratory at Hadassah University Hospital-Mt. Scopus.
However, the symptoms brought on by PTSD – like sleeping disorders, difficulty in concentrating, irritability, nightmares and flashbacks to the traumatic event – may not emerge sometimes until four months after the event, and may persist months and years later.
The researchers discovered unique biomarkers in blood taken from patients treated in at the Hadassah emergency room just hours after being exposed to a traumatic event. This physiological “signature” has been found to accurately identify the 12 percent or so of patients will develop PTSD. The results of the team’s findings were published in the prestigious journal Molecular Psychiatry.
“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 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.”
The test group included 24 people who were diagnosed as ‘shock casualties’ in the emergency room after experiencing a traumatic event. Blood samples were taken in the emergency room and again four months later. Shalev said that they did not take blood from trauma victims who suffered physical harm because they wouldn’t have been able to prove that the biomarkers were not affected by medications and treatments that they underwent in the emergency room.
Of the 24 blood samples, certain biomarkers were found in 12 of the patients both in the emergency room and four months later. When all two-dozen patients were followed up four months later – generally considered the period after a traumatic event when PTSD sets in – the same 12 patients were diagnosed clinically with PTSD; the other 12 had none of these biomarkers.
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.
Shalev said that future plans include replicating the findings on an independent sample, with more advanced micro arrays than those. He also hopes to find specific ‘disturbed’ genes that truly contribute to the occurrence of PTSD, and thereby understand the occurrence of the disorder and come up with eventual ideas about remedy.
“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 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.”
“Research is like climbing the Himalayas – the further one gets into the mountains – the steeper the slope becomes, the view gets better and better, and one has to be supplied with more oxygen. Thus the challenges ahead of us are major on both organizational and hypothesis testing levels.”