Researchers say they\u2019ve found a gene that appears to increase or decrease the risk of post-traumatic stress disorder among combat vets.<\/p>\n
If this study can be replicated, it could help answer the question of why one soldier experiencing trauma develops PTSD while another does not. That, in turn, could lead to ways to boost stress resilience.<\/p>\n
\u201cWe\u2019re really excited about this because it may help us open a new paradigm between PTSD and TBI,\u201d says Dr. Mark Miller, a clinical and research psychologist with the VA’s National Center for PTSD and an associate professor at Boston University School of Medicine. \u201cPeople studying TBI-related impairments have found that TBI and PTSD are often highly correlated. What we\u2019re thinking is that there may be some commonality that has a molecular basis to it. I\u2019m kind of anticipating that next decade or so will show lot of advances in neuroprotective and neurodegenerative responses.\u201d<\/p>\n
Miller and his team recently published an article in \u201cMolecular Psychiatry\u201d which explained the work they did in what\u2019s believed to be the first genome-wide scan for genetic risk factors associated with PTSD. Their work followed up on studies of twins which showed that sensitivity to stress could be inherited, that it wasn\u2019t totally a function of stress in the environment.<\/p>\n
First came DNA samples from 496 military veterans and 233 of their spouses; 53.7 percent of the participants met the criteria for PTSD. \u00a0Then the researchers analyzed genetic data for association with PTSD using a microarray chip that contained probes for 2.5 million SNP (single-nucleotide polymorphisms) spread across the entire genome<\/p>\n
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\u201cSNPs are rungs on the ladder of the DNA double helix called base pairs where there is known variation across humans,\u201d Miller told me. That allowed researchers to see if the stressed vets shared any common genetic difference.<\/p>\n
It turned out that they did, and it wasn\u2019t a gene that Miller and his team were familiar with. They found a statistically significant association with a variant of the retinoic acid orphan receptor A (RORA) gene, which was unfamiliar to them at the time.<\/p>\n
\u201cRORA has never been linked to PTSD before to our knowledge,\u201d said Miller, the study\u2019s lead investigator. \u201cBut when we read up on it, we found that it had previously been linked to other disorders such as attention-deficit hyperactivity disorder, bipolar disorder, autism and depression. In other words, it was a psychiatrically relevant gene.\u201d<\/p>\n
One of the major roles of RORA is protecting brain cells from the damaging effect of injury and disease and possibly traumatic brain injuries, Miller told me. He believes RORA produces a protein that helps protect neurons from neurotoxic effects of stress, including oxidative stress. An imbalance between oxidants and antioxidants in a cell, oxidative stress can be caused by physical damage or traumatic stress.<\/p>\n
\u201cOur hypothesis is that those who have the RORA risk marker may have a RORA gene that is less capable of mounting a neuroprotective reaction to stress, causing structural damage and functional changes to neurons that RORA should be protecting,\u201d said Miller.<\/p>\n
Again, this is a new study that hasn\u2019t been replicated, but if future studies bear out its findings, researchers may be able to develop gene therapies or pharmaceutical ways to enhance the function of the RORA gene. And that may help stress-vulnerable people become more resilient.<\/p>\n
Incidentally, the genome-wide association study is an extremely broad-based look at all associations, rather than a selective look at just some of the usual suspects \u2013 specifically the dopamine and the serotonin systems.<\/p>\n
\u201cWe looked at the serotonin transporter valve and didn\u2019t see any strong association,\u201d Miller told me. \u201cHowever, there\u2019s plenty of literature supporting its importance. The caveat goes back to the limitations of GWAS. We have to apply such a strict statistical threshold that many lesser associations had to fall by the wayside. The fact that we didn\u2019t find it in this study doesn\u2019t mean it doesn\u2019t play a role in the general population or in a population substrata.\u201d<\/p>\n