JUDY WOODRUFF: We have a science story about the search for effective treatments for post-traumatic stress disorder, or PTSD. It comes from WTTW Chicago Tonight, and is reported by Jay Shefsky
JAY SHEFSKY, WTTW correspondent: On the face of it, the cause of post-traumatic stress disorder seems obvious. If you live through a terrifying event, you may be left with fears and memories that can take over your life. What’s not so obvious is how PTSD could be prevented once someone has experienced the trauma.
Well, Northwestern scientist Dr. Jelena Radulovic thinks the key to preventing PTSD may lie in understanding the emotion of fear on a molecular level. She runs what they call the fear lab at Northwestern’s medical school.
DR. JELENA RADULOVIC, Northwestern University: In most (inaudible) so many levels in terms of psychology and cognitive science and neurobiology and neuroscience. So we study the molecular basis of fear.
SHEFSKY: In this study, they wanted to figure out the chemical changes that occur in a brain as it develops PTSD. They did this by looking at the brains of mice, but first, they subjected the mice to severe stress in two stages. In stage one, they immobilized the mouse for an hour by taping it to a board.
RADULOVIC: It’s a very well established and most widely used model of distress. It doesn’t cause pain in the animals, but it causes significant discomfort.
SHEFSKY: Stage two comes six hours later, when the mouse gets what Dr. Radulovic calls fear conditioning.
RADULOVIC: For fear conditioning, we place the animals in the box, and it freely explores the box for three minutes.
RADULOVIC: And after three minutes, it receives the mild shock for two seconds, and that’s it.
SHEFSKY: Dr. Radulovic says they designed the study with two stages because PTSD in humans is more likely to come from a series of events, not just a single trauma.
RADULOVIC: You have an earthquake, for example, which is a direct threat to your own life, and then while you have survived it, you still see that most people you know haven’t survived or are wounded or have suffered horrible injuries, so there is a strong physical stressor, which is followed by a series of emotional stressors.
SHEFSKY: And sure enough, if a mouse is subjected to both stages, being immobilized and then being shocked, it acts much more scared when it’s put back into the box where it was shocked. The researchers know this by measuring the amount of time the mouse stands frozen.
This mouse, for example, was shocked but had not been previously stressed by being strapped down. Now that it’s back in the box where it was shocked, it freezes 40 to 50 percent of the time. They say that’s a normal amount of fear after a bad experience.
Now, this video shows one of the mice that got both stages, stress and fear conditioning.
RADULOVIC: They freeze 80 to 90 percent of the time, and not only that their fear is intense, it’s also lasting because they can show this freezing for up to a month, and one month is a long time in the life of a mouse.
SHEFSKY: The final step involved looking at the mouse’s brain.
Thin slices were placed on slides to be examined under a microscope to try to understand on a molecular level what happens between the two stages of trauma. What they saw was this: When the mouse experienced the first traumatic event, being strapped down, its brain developed a kind of ongoing frenzied interaction between two proteins. That would calm down eventually, but if another traumatic event occurs within about six hours, the frenzied loop continues, and the memories and the fear become more strongly entwined.
So the question was this: Could researchers find a drug that would stop that frenzied protein interaction before the second traumatic event takes place, and would that prevent the PTSD?
A drug like Valium might work, Dr. Radulovic says, but that would come with side effects and the risk of addiction.
RADULOVIC: So we try to find a drug that would not cause side effects, which would keep memories normal, which would not cause sedation, and that would decrease fear.
SHEFSKY: They tried two newly developed anti-anxiety drugs called MPEP and MTEP. And the results were surprisingly effective. If the mice were injected with the drugs within five hours after the first stressful event, there was no sign of PTSD after the second event.
RADULOVIC: We first started very modestly, testing the inhibitor immediately after threat, and one hour later, three hours later, and we were very surprised and very positively surprised when we saw that the drug was effective also five hours after the end of stress.
SHEFSKY: Again, here is the video of the mouse that has been through both traumatic events, but received no drug. And here is a mouse who has received the drug. They say it behaves exactly as if it had never been through that first traumatic experience.
Animal studies, of course, always raise ethical questions. The thought of subjecting mice to stressful and frightening experiences and then killing them to examine their brains is controversial. I asked Dr. Radulovic to address the ethics of this study.
RADULOVIC: We are considering ethical problems all the time in the lab, and we are designing the experiments so that there is a minimal possible distress incurred to the animals in order to model human disorder.
SHEFSKY: But will this finding hold true for humans? While the drugs they used in the study are not yet approved for human use, there is one she says that is closely related, so a human trial could come relatively soon.
RADULOVIC: It was developed as a clinical drug for treatment of anxiety and not for prevention, so we believe that the drug can have a high potential in the prevention of the disorder.
SHEFSKY: And the results of this study can hardly come soon enough. While current PTSD sufferers would not be helped by this drug, perhaps the time will come when many of the thousands of new cases each year could be prevented.
GWEN IFILL: That report came from our colleagues at Chicago Tonight.