Epigenetic changes show up in people with PTSD

People with post-traumatic stress disorder seem to accumulate an array of chemical modifications to their DNA that are different from those found in healthy people, researchers report online May 3 in the Proceedings of the National Academy of Sciences.

The new findings, while showing differences between people with and without PTSD, don’t shed light on whether these differences might play a role in PTSD, says study coauthor Sandro Galea, a physician and epidemiologist at Columbia University in New York City.

Only a fraction of people who witness a traumatic event develop PTSD. In an attempt to identify what makes people who develop PTSD biologically different from those who don’t, Galea and his colleagues obtained blood samples from 100 people in the Detroit area. All had been exposed to at least one potentially traumatic event, and 23 were diagnosed with PTSD. The scientists tested 14,000 genes in these blood samples for chemical changes to DNA that can affect gene activity without altering the genetic information itself.

The researchers focused on the methylation of genes, a process in which a methyl molecule is added to DNA, typically turning off a gene and inhibiting production of the protein that the gene encodes. If people with PTSD have more or less methylation in specific genes, that might somehow contribute to PTSD, Galea says.

The team found that the people with PTSD showed less methylation in several immune system genes and more methylation in genes linked to the growth of brain cells. “There is evidence that PTSD is involved in immune dysfunction, and we suggest that that’s part of a larger process,” Galea says. Although previous studies have also suggested a PTSD link to immune gene activation, the connection is unclear.

“This is interesting data, but there are a lot of things still to do,” says Manel Esteller, a molecular geneticist at the Bellvitge Institute for Biomedical Research in Spain and the University of Barcelona who was not part of the study. “What’s missing is an explanation of how the traumatic stress really causes these changes in methylation — what is the mechanistic link?”

What’s more, the sample size of 23 patients is small, and PTSD diagnosis is tricky, says Naomi Breslau, a sociologist and epidemiologist who studies PTSD at Michigan State University in East Lansing. “I don’t believe this can be taken as a breakthrough.”

Galea agrees that finding the mechanisms involved will be the key to determining whether these methylation differences matter for PTSD. If further research clarifies how these changes play out in the body, he says, “that may allow us to eventually do something about it.”