Researchers have just identified a drug capable of preventing memory problems and increased anxiety in traumatized mice suffering from PTSD-like symptoms.

The finding has huge medical implications for future human PTSD (post traumatic stress disorder) treatment and/or prevention.

According to Howard Hughes Medical Institute investigators, a receptor called Oprl1 is altered when mice experience PTSD symptoms. The scientists then developed a drug that targets that specific gene, thus preventing the development of the disorder.

Mice were put through a traumatic event – being restrained to wooden boards – and were at a heightened state of fear.

The researchers then gave the mice the Oprl1-targeted drug and found that it had a preventive effect on PTSD and a significant impact on fear memory modulation.

The study, which was published in the journal Science Translational Medicine, indicated that humans with genetic variants of the Oprl1 gene are at a higher risk of developing PTSD after a traumatic event, suggesting that the new drug could have a similar effect in humans.

Study leader, HHMI investigator Kerry J. Ressler of the Emory University School of Medicine, said:

“PTSD is a tractable problem that can be prevented and treated if we put our mind to it. Bringing neuroscience and genetic approaches together provides a powerful way to understand this debilitating illness.”

PTSD is a severe anxiety disorder brought on by direct experience of traumatic events – the NHS (National Health Service) in the U.K estimated that about 40% of sufferers developed PTSD after a loved one died suddenly. A sufferer’s life may be completely disrupted, by reliving the horrific event through nightmares as well as flashbacks. Approximately 5% of men and 10% of women suffer from PTSD at some point in their lives.

Military veterans who served in combat are at a particularly high risk of developing the disorder. Researchers believe that the PTSD rate among armed forces who served in Iraq could be as high as 35%, according to a study published in the journal Management Science.

US Soldier in Iraq
Military personnel are at the highest risk of developing the disorder

Even though there are medications, as well as psychotherapy, that can help alleviate the symptoms of PTSD, researchers are trying to find ways of preventing the disorder from developing in the first place.

Ressler and his team set out to identify genes linked to the development of PTSD in mice. They made a group of mice undergo a traumatic event, which triggered a range of PTSD symptoms in some and milder fears in others. The mice that were extremely traumatized showed signs of anxiety, stress and confusion, which are very similar to the symptoms of PTSD in humans.

The researchers used a state-of-the-art screening method to analyze hundreds of genes in the mice and identify any major changes in patterns of gene expression. They found that there was one gene in particular that turned down in the PTSD group of mice compared to the group that didn’t undergo trauma. The gene, OPRL1 (opioid receptor-like 1), is a nociceptin receptor responsible for regulation of numerous brain activities, including pain processing.

In order to see whether activating the receptor with a drug could help prevent the development of PTSD, the scientists used a newly developed compound from the Scripps Research Institute that activates the receptor.

The drug they developed successfully prevented the development of PTSD symptoms in the laboratory animals.

Following this finding, the team wanted to determine whether Oprl1 could be linked to PTSD in humans. They analyzed the gene’s sequence in 1,800 people who were severely traumatized – some diagnosed with PTSD and others without the disorder.

There was one variant of Oprl1 that was more common in those who suffered from PTSD. Through a series of brain scans the scientists confirmed that people with that specific gene variation had altered patterns of fear-related neurological activity.

Ressler said: “There are likely many, many genes that are involved in the risk for PTSD following trauma, Oprl1 may be one of the many genes that contribute risk, though larger samples and replication studies are required to be certain of this.”

The team is now planning to conduct a series of follow-up studies to further understand the role Oprl1 plays in humans.

Ressler concluded:

“For any drug used to prevent PTSD, we would want to know who was most at-risk based on psychological and biomarker approaches. We would then predict that if we gave those individuals such a drug within a few hours after trauma, it would prevent the development of PTSD pathology.”

A previous study published in Biological Psychiatry revealed that increasing the presence of glucocorticoids may also reduce the risk of developing post-traumatic stress disorder (PTSD). Glucocorticoids, including cortisol, are a group of stress hormones that increase after experiencing stress, which may also prevent the prevalence of PTSD.

Written by Joseph Nordqvist