Turning to Biomarkers to Put TBI Symptoms in the Past
Could the brain provide biological clues following a traumatic injury that would improve the outcome for the patient?
The George Washington University (GW) Hospital is partnering in a new study to determine whether biomarkers in a patient who has suffered a traumatic brain injury (TBI) can help reduce the risk of post-TBI symptoms such as post-traumatic stress disorder. TBIs account for the onset of PTSD in approximately 700,000 Americans each year. Depression and post-concussive syndrome (PCS) are also common in patients who develop PTSD. Research suggests, however, that if the determinants of risk are better analyzed and understood there is a better chance of successful preventive interventions.
Along with Walter Reed National Military Medical Center (Walter Reed) and the National Institutes of Health, GW’s School of Medicine and Health Sciences (SMHS) Department of Neurological Surgery is collaborating in a study funded by the Henry M. Jackson Foundation for the Advancement of Military Medicine. Jessica Gill, PhD, of the National Institute of Nursing Research, is serving as principal investigator. Gill has been exploring the mechanisms underlying neurological symptoms and deficits in military personnel with TBIs, as well as athletes with concussions. This line of inquiry employs a cutting-edge type of biomarker harvesting technology using a nanoparticle capture platform in a prospective sample of patients immediately following a trauma.
Findings from her research will identify the clinical and biological risks that predict PTSD onset and neurological compromise following a traumatic injury.
SMHS serves as a site for sample collection from civilian patients. Gill is joined on the Jackson grant by Anthony Caputy, MD, chair of the Department of Neurological Surgery and Hugo V. Rizzoli Professor of Neurological Surgery at SMHS, and Babak Sarani, MD ’97, RESD ’04, director of the Center for Trauma and Critical
Care at GW Hospital and associate professor of surgery and of emergency medicine at SMHS. The subjects are individuals who have had a severe closed (non-penetrating) head injury resulting from a fall, a car accident, or an assault, to name some examples.
Researchers are collecting specimens from these patients, specifically blood and cerebrospinal fluid, in order to search for these biomarkers that could predict an outcome. By examining the proteins and lipids in the serum of the cerebrospinal fluid they hope to determine if the level of consciousness changed.
Current scanning technologies — CT, MRI, and other techniques — do not necessarily reveal what’s happening at the molecular level in the brain. According to the researchers, some small evidence of head injury can be observed in these scans, but it’s not that good and not very predictive of the patient’s long-term outcome. The goal of the project is to identify a molecular marker to correlate with clinical examinations and imaging findings to better predict patient outcomes and improve their care.
Gill’s research suggests that DNA methylation may be a putative biomarker of psychiatric risk, as it reflects long-term changes in the function of the gene and may shape the recovery ability of the TBI patient through changes in cell function. Moreover, the neuroendocrine system appears to have a determine role. Prior research has shown that both PTSD and depression are associated with endocrine alterations, “leading us to question if this biological change may underlie vulnerability for the onset of PTSD as well as depression and post-concussive syndrome following a TBI,” according to Gill’s hypothesis. “In support of the idea of shared vulnerability, patients with a TBI also often display endocrine function alterations.”
Samples are still being collected at GW, from approximately 50 individuals, ages 18 to 65, and data continues to be tabulated and analyzed at the NIH.