Could a new discovery pave the way for a resilience-boosting drug?
Camp Mackall, North Carolina, is home to the US Army’s ‘survival school’. Here, soldiers take part in survival, evasion, resistance and escape (SERE) training. This is among the toughest of all US military training programmes. Take the resistance component. At a mock prisoner-of-war camp, complete with concrete cells, razor wire and fake graves, ‘prisoners’ are put through simulated interrogations that generate “intense and uncontrollable stress”, in the words of a journal paper by a team led by Professor Dennis Charney and Professor Steven Southwick, of Mount Sinai School of Medicine and Yale University respectively.
Charney and colleagues realised that the survival school was a perfect controlled environment for the study of acute stress on the human body. They got permission to expose regular and special forces soldiers to tests before and after the training, and before and immediately after mock interrogations. These tests revealed that blood levels of a brain chemical called neuropeptide Y (NPY) correlated strongly with the soldiers’ ability to cope. Those with more NPY performed better during the interrogations. What’s more, the special forces soldiers, known for being especially cool under stress, had significantly higher levels of NPY compared with regular troops, both before and after the training. Twenty-four hours after the programme had finished, NPY levels in the special forces soldiers were back to their baseline, while those in regular soldiers were still considerably lower.
NPY is triggered by stress. It helps to curb the release of the hormone noradrenaline, which plays a crucial role in the fight-or-flight response. So more NPY means you should recover from stress faster – and so, in theory, be more resilient. Countless animal studies have shown that doses of NPY can reduce anxiety and fear. “[We have] thousands of papers on NPY in animals. Then we have this observation in humans, and then there’s the genetics,” says Charney. The genetic work suggests that people who have a form of NPY gene that means they naturally produce less are more prone to anxiety. Variations in NPY, then, seem to be important for understanding the neurobiology of resilience, Charney says.
The obvious next question is, what happens if you give NPY to people? Could NPY in drug form boost resilience? Or even treat post-traumatic stress disorder (PTSD)? Charney and his colleagues have created an NPY nasal spray. They tried giving patients with PTSD a single dose. As this had never been done before, the dose was low, “and we weren’t seeing much,” Charney says. Then, in 2013, another paper came out on rats, which showed success with a nasal spray at what would be a much higher dose for people than Charney’s team had used. Seven days after being put through a traumatic experience, rats that had got a dose of NPY right before the trauma, or immediately afterwards, showed significantly fewer signs of depression and anxiety than untreated rats.
In spring 2014 the US Food and Drug Administration granted approval for Charney’s proposal to try higher doses with PTSD patients. This research is now taking place. By spring 2015 “we’ll know if it works – or not,” Charney says.