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PTSD may be prevented, researchers find

Scientists identify a gene in traumatized mice that is also linked to post-traumatic stress disorder in humans – and find that a drug can treat symptoms in mice by triggering a key brain receptor.

June 05, 2013|By Alan Zarembo, Los Angeles Times
  • U.S. soldiers take part in an operation in support of Afghan soldiers in Wardak province, Afghanistan.
U.S. soldiers take part in an operation in support of Afghan soldiers in… (Carolyn Cole, Los Angeles…)

Experts estimate that up to 20% of U.S. troops returning from Iraq and Afghanistan suffer from post-traumatic stress disorder, a condition that can be stubbornly difficult to treat.

But what if PTSD could have been prevented in the first place?

Scientists have done something similar in traumatized mice. Days after a harrowing experience being restrained on wooden boards, they were given a drug that triggers a brain receptor thought to be involved in how mice — and people — respond to fear.

"We prevented PTSD-like symptoms," said Emory University neuroscientist Raul Andero Gali, lead author of a study published Wednesday in the journal Science Translational Medicine.

The study raises the possibility that similar drugs could one day be given to people after combat, car accidents or other types of trauma. The prospects for developing such a treatment are very good, said Sheena Josselyn, a neuroscientist at the University of Toronto who was not involved in the research.

Andero's team set out to find genes that could help explain why some trauma victims are more vulnerable to PTSD, an anxiety disorder in which they continue to feel stressed or frightened even when they are no longer in danger.

The scientists taped mice to the wooden boards for two hours each — a technique known to cause PTSD symptoms, including learning and memory problems and anxiety.

The researchers later killed the animals, along with a control group that had not been subjected to the trauma.

That was followed by the removal of amygdala tissue, a region of the brain that plays a key role in the formation of emotional memories. Using a sophisticated screening method, the researchers combed through tens of thousands of genes and looked for differences in how the two groups of mice expressed those genes.

One stood out. Known as OPRL1, it contains instructions for making a receptor for a brain chemical called nociceptin.

The scientists wondered whether activating that receptor with a drug would have any effect on the development of PTSD symptoms.

So they traumatized more mice and then trained them to expect a mild electric shock after hearing a 30-second tone. Some of the mice received injections of the drug.

The next day, researchers repeatedly played them the tone but did not give them the shock.

Mice that had received the drug quickly learned not to fear the tone. The untreated mice, however, continued to freeze in place and act in other ways that indicated they were still traumatized.

In short, activating the nociceptin receptor appeared to dampen a process known as "fear memory consolidation."

In the final step of their study, the scientists examined the OPRL1 gene in more than 1,800 people who had suffered trauma as children and had PTSD. Those who had a specific — and relatively common — version of the gene had worse PTSD symptoms.

In addition, 110 of the childhood trauma victims were blasted with air when certain shapes were displayed on a monitor — an effort to train them to recognize those shapes as danger signals.

Then their fear responses were monitored as they were shown a different series of shapes without any air blasts.

Trauma victims who had the particular version of OPRL1 were not as good at distinguishing between the dangerous shapes and the safe ones.

In a commentary published with the study, two experts on trauma-related mental health disorders wrote that variations in the OPRL1 gene might one day be used to predict who is at greatest risk for PTSD and to guide their treatment.

Dr. Karen Seal of UC San Francisco and Dr. Murray Stein of UC San Diego also noted that the findings were consistent with observational studies suggesting that trauma patients who receive morphine are less likely to develop PTSD. Morphine acts on a brain receptor that's related to the one targeted in the new study.

But Rachel Yehuda, a neuroscientist and PTSD expert at Mount Sinai School of Medicine in New York, questioned whether it made sense to block the brain's natural responses to stressful situations.

"Some of these responses are there to protect the body and mind," she said. "I am not sure that I would want a soldier in the field to go to combat without his fear response, because this might actually kill him."

alan.zarembo@latimes.com

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