Systems Biology Studies for Biomarkers of Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Left untreated, PTSD can be life-threatening, as it is often linked with substance abuse and severe depression. Consequently, the identification of PTSD indicators (“biomarkers”) that can be detected in the blood or non-invasively is of great interest. Using both a social defeat mouse model of PTSD and minimally invasive data taken from U.S. Army veterans, we aim to identify biomarkers that aid in both the diagnosis and assessment of prognosis of individuals with PTSD. To do this, we use two complementary systems biology strategies: (1) application of statistical and machine learning approaches for building networks of interacting genes related to disease progression, and (2) construction of mechanistic mathematical models of PTSD-relevant neurological circuits. As a result of these strategies, we have constructed both a PTSD “Brain Core Module Network” and a “Fear Conditioning Neuro-Circuit Model” that together suggest many candidate biomarkers relevant to the PTSD disease mechanism.