How Genetic Makeup Can Influence Outcome After a Brain Injury

Dr. Jordan Grafman talks about the Vietnam Head Injury Study, started in 1981, that continues to look at the effects of brain injury on current and late-life function.

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I first became involved in studying people who had penetrating brain injuries in 1981 when I was in the Air Force. I was assigned to Walter Reed Army Medical Center just at the beginning of a study called the Vietnam Head Injury Study, and I was assigned to that study. That study was the first study really to look at the effects of traumatic brain injury in Vietnam veterans. We were able to see 525 Vietnam veterans who had brain injuries--almost all penetrating brain injuries-- and a number of other Vietnam veterans who had the same amount of combat, the same pre-injury intelligence scores, and we were able to bring them in for comparison purposes. They all came to Walter Reed for 1 week, and we started studying them at that time. So, originally we studied the Vietnam vets from 1981 to 1985 at Walter Reed, but we knew in the future we wanted to bring them back. At the time we studied them at Walter Reed, it was more or less about 15 years after their original injury, so we decided in around 2002 to bring them back for what we called Phase 3, and at the time we all believed that it would be important to try to look at in essence their genetic makeup and how that influenced their recovery of function, and late-life functioning. We were able to get their permission to draw blood when they came for this Phase 3 evaluation, which was conducted at the National Naval Medical Center. And as a result of doing that, we've learned a little bit about the contributions of genetic predisposition to outcome. We know that there are variants in individuals of any single gene. We all share the same genes, but there are individual differences in how those genes express themselves, and you can have 1 allele of a gene--1 type of gene--or I can have another type. It's the same gene, but a slightly different variation on the gene. So, it turns out that if you have 1 variant of a gene--a polymorphism, it's called-- you may actually perform better on a task than if you have the bad variant, and we were able to show that in our Vietnam vets on tasks ranging from global tests of intelligence to tests of so-called executive functions, and in the case of where you had the bad gene and you had a brain lesion your performance looked like what we would expect. On average, it's about 1-1/2 standard deviations below the average score of somebody who never had a brain injury. That's a significant difference, and it's something that was known in the literature already. What was more surprising is if you have the good gene, you looked just like the healthy, non-traumatic, brain-injured control, even if you had a lesion the same size as the person who had the other variant of the gene and performed poorly. It suggests that if you have the right version of a gene that's concerned, for example, with neuroplasticity--the reorganization of the brain after brain injury-- if you have the good version of that gene it would predict that you would do better in the long run. If you use this information in triaging a patient, it might tell you who's more likely to benefit or who needs therapy more than somebody else, and you might have a more intensive effort with somebody who has, for example, the bad version of that gene concerned with plasticity. So, that's something that's very important. Genetic information is important. It can teach us it should be part of the evaluation--I believe, certainly in the future--of people who have traumatic brain injury, but we should always remember that it's not your destiny. It's just a pointer to what to be aware of potentially.
Posted on BrainLine February 11, 2013.

Produced by Victoria Tilney McDonough, Justin Rhodes, and Erica Queen, BrainLine.