PTSD's inflammatory pathway
Study focuses on disorder’s effect on immune system
By Chris Horn, email@example.com, 803-777-3687
After 15 years of nearly continuous combat operations in Iraq and Afghanistan, post-traumatic stress disorder has become part of our everyday language, a phrase that captures the human psychological response to horror.
But while it is a familiar acronym, the disorder’s full effect on the body isn’t well understood. Mitzi Nagarkatti, chair of the pathology, microbiology and immunology department at the School of Medicine Columbia, has launched a five-year study to investigate how PTSD affects the immune system, particularly the inflammation cascade that can lead to cardiovascular disease, obesity or diabetes. Her lab was the first in the world to document epigenetic changes in combat veterans returning from the Persian Gulf, Iraq and Afghanistan wars.
“PTSD patients frequently have very high levels of pro-inflammatory cytokines and chemokines that induce inflammatory disease,” Nagarkatti says. “We’re looking at the mechanisms by which these immunological changes occur, especially epigenetic mechanisms.”
The $2.4 million study, funded by the National Institutes of Health, will analyze blood samples collected from a Detroit-area health system, some of which came from residents diagnosed with PTSD. Some of the neighborhoods from which the blood samples were collected have PTSD rates twice that of the general population.
The study will compare blood samples from three groups: those with PTSD, residents who have been traumatized but don’t exhibit signs of PTSD and residents who have not been exposed to extreme stress or trauma.
If we can develop a kind of fingerprint of PTSD, then we would have a diagnostic tool to say, ‘OK, this individual is more susceptible to developing PTSD so we need to consider giving this inhibitor.’ We could also measure how well a patient is responding to treatment by looking at what is happening at the molecular level.
Mitzi Nagarkatti, professor and chair, School of Medicine Columbia
Nagarkatti’s team will focus on the epigenome, the molecules including micro-RNA that affect the human genome and, ultimately, the immune system. Nagarkatti is interested in determining the precise pathways by which immune cells get activated and begin to cause chronic inflammation and damage to tissues and organs.
“Once those pathways of epigenetic activation of the immune system are better understood, new therapeutic interventions could lead to earlier diagnoses of PTSD, better treatments and even prevention of the disorder,” Nagarkatti says — therapeutic interventions could include inhibitors that block key aspects of the inflammation pathway that PTSD triggers.
“We have preliminary data to suggest some aspects of the epigenome could be manipulated so as to prevent some of the outcomes,” Nagarkatti says. “When we can target those — particularly the micro-RNA — by using certain inhibitors, we can prevent disease outcomes.”
Ultimately, Nagarkatti wants to develop diagnostic and prognostic tools and new interventions that can be used as preventative or therapeutic agents. The next-generation genome analyzer the team is using can reveal a highly fine-grained picture of chemical changes in the blood samples.
“If we can develop a kind of fingerprint of PTSD, then we would have a diagnostic tool to say, ‘OK, this individual is more susceptible to developing PTSD so we need to consider giving this inhibitor,’” Nagarkatti says. “We could also measure how well a patient is responding to treatment by looking at what is happening at the molecular level.”
Nagarkatti’s research team published a paper on its initial findings from the study in Scientific Reports last year. At this year’s annual meeting of the Society of Toxicology, attended by more than 6,500 scientists, it was named "paper of the year."
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