PHILADELPHIA — An interdisciplinary team of researchers from the Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia (CHOP), including specialists in neurobiology, psychiatry, and biomedical imaging, have received a $3.5 million grant from the Defense Advanced Research Projects Agency (DARPA)* to study how to enhance stress resilience in military personnel.
"This is an exciting opportunity to rapidly translate basic science results on brain circuitry and biomarkers of stress resilience from animal models into human populations" said the study's principal investigator, Seema Bhatnagar, PhD, assistant professor of Anesthesiology and Critical Care at Penn/CHOP. "The goal of these studies is to identify and validate novel treatment strategies that target significant health problems in military personnel, particularly post-traumatic stress disorder (PTSD). Such strategies have potential application for treating psychiatric health problems in individuals in the general population as well."
The new studies build on previously funded Penn/CHOP DARPA Phase 1 basic research. In the previous studies, the team examined neural circuits in the brain that are affected by stress exposure and how these circuits, in turn, can lead to dysfunction in physiology and behavior. From those investigations, the researchers were able to identify targets that could enhance resilience to stress and biomarkers of resilience to stress.
In the second phase, the team will validate the stress-resilience targets and test new stress-management strategies. The research will involve both basic research and translational studies and will also involve active duty personnel and veterans being treated for post-traumatic stress disorder (PTSD) at the Philadelphia VA Medical Center and two other military institutions. The Penn/CHOP team is one of two awardees in the nation to receive Phase 2 funding for their work.
"PTSD is a common and often disabling condition that is a direct outgrowth of extremely stressful experiences. Yet we know that, exposed to similar stressors, some people develop PTSD while others do not," said Mitchel Kling, MD, associate professor of Psychiatry at Penn. "The clinical and translational studies to be done in the second phase of our research will allow us to directly test the relevance of findings from the preclinical studies to the evaluation and treatment of individuals with PTSD and better illuminate the complex genetic and environmental underpinnings of PTSD."
The ultimate goal of the new Phase 2 studies is to help identify the types of events that produce the most severe psychological problems and to identify vulnerable individuals that could benefit from early treatment, or to prime these individuals to prevent these problems from emerging in the first place. The new research may also help to identify those individuals who need specific types of treatments, whether psychological, pharmacological and/or rehabilitative.
The team will also look into the effects of currently administered drugs in promoting stress resistance or stress vulnerability. Many of these drugs are currently approved by the Food and Drug Administration (FDA) and prescribed for common medical conditions such as hypertension. The findings could lead to the development of novel pharmacological and other types of treatment strategies for psychological health problems.
"The new, integrative approach implemented in our studies has exciting potential for providing a more complete depiction of both the kind and degree of brain pathology in these disorders" said James Gee, PhD, associate professor of Radiology at Penn. "The unique expertise of our multidisciplinary team is critical to the success of this ongoing research initiative."
Co-Investigators of the research teams include Ted Abel, PhD, Sheryl G. Beck, PhD, Rita Valentino, PhD, at Penn/CHOP and Phillip Gehrman, PhD, Paolo Nucifora, MD, PhD, and Richard Ross, MD, PhD, at the Philadelphia VA Medical Center/Penn as well as Investigators at Camp LeJeune and the National Intrepid Centre for Excellence at the Walter Reed National Military Medical Center.
*This document was cleared by DARPA on March 5, 2012. Approved for Public Release, Distribution Unlimited.