Christine E. Marx, M.D.; Duke University Center and VA Medical Center of Durham, N.C.; PTSD/TBI INSTuST Clinical Consortium Award

PTSD and TBI affect very large numbers of servicemen and women and there's a really urgent and acute need to develop better treatments for PTSD and TBI.

They affect very large numbers of people and until recently have not been allocated the proportional resources to develop an understanding of their neurobiology and their optimal treatment.

We were granted a consortium award as one of 10 clinical sites that are part of a larger consortium headed by Mary Stein at the University of California at San Diego. And we're going to be participating in clinical trials trying to develop new treatment modalities for both PTSD and TBI.

My collaborator in that is Dr. Gerald Grant in the Department of Neurosurgery at Duke and as well as other collaborators across the country.

We focus on molecules called neurosteroids, which are endogenous molecules that are enriched in the brain that have a number of properties that make them very interesting targets for the treatment of PTSD and other disorders. A particular neuro-steroid, allopregnanolone has a number of properties that make it an interesting target for the treatment of psychiatric disorders. Specifically it increases neurogenesis; it decreases inflammation in animal models. It also is neuroprotective in rodent models of traumatic brain injury.

It is increased following the administration of selective serotonin reuptake inhibitors and so one of the hypotheses in the field currently is that neuro-steroid induction contributes to the therapeutic efficacy of a number of agents that are used in psychiatric disorders including PTSD and schizophrenia.

Allopregnanolone is also relevant to the stress response; it's increased following acute stress and it is thought that it feeds back to return an organism to a homeostatic state. Allopregnanolone levels are inversely related to psychiatric symptomology, specifically the lower the allopregnanolone levels the higher the symptoms of PTSD and the higher the symptoms of depression.

The hypothesis is that replenishing this molecule may have some clinical efficacy and may be therapeutic, potentially representing a new treatment approach that has multiple mechanistic possibilities.

Ganaxolone is a synthetic neuro-steroid analog of allopregnanolone, and it has a number of properties that make it a very interesting molecule to test for the treatment of PTSD. We've designed a randomized controlled trial utilizing ganaxolone to determine if this molecule has possible efficacy for the treatment of PTSD.

The VA definitely informs our research endeavors. Having a clinic that serves OEF-OIF veterans has been a really pivotal component of our efforts to understand these disorders better, to understand their neurobiology, to understand how this cohort may be different from prior cohorts who have been deployed, and it's an opportunity to serve the veterans who have made great sacrifices and to try to develop new treatments that will hopefully be helpful in the future.

Although much of the focus of these efforts are on servicemen and women, they have very important ramifications for these disorders in the general population. TBI is a relatively understudied area; it's extremely common. The numbers of people who sustain a TBI are very large. PTSD, lifetime prevalence in the U.S. is approximately 7%. So the research that emerges from these efforts I think will have far-reaching ramifications not only for servicemen and women but also for the population in general.