Translational Methods For Ptsd Research PDF Download

Development of clinical diagnostic criteria has driven progress since the paradigm shift in psychiatric care toward modern medical practice in the mid-20th century. This shift toward a biological understanding of psychiatric disorders led to the discovery of drug-treatment options, but has yet to lead to definition of any clinical biomarkers for psychiatric disorders. Due to advances in genomics, metabolomics, and neuroimaging methods, biomarker discovery has become a major research focus. In clinical studies this has centered around comparing patient population to control populations. However, in the case of post-traumatic stress disorder, comparison of patient populations with healthy controls has been shown to highlight differences in the populations that may be independent of PTSD diagnosis. Twin studies have shown that many factors found in past PTSD studies were also characteristic of the non-PTSD diagnosed healthy twin. This is cause for skepticism toward the results of clinical trials where biomarkers of psychiatric disorders are being studied, as they may not differentiate diagnostic biomarkers from susceptibility biomarkers. Preclinical studies done using psychiatric disorder models will be critical in biomarker discovery due to the complexity of studying psychiatric disorder development and of structuring studies that can delineate different types of biomarkers in humans. This work leveraged an animal model of post-traumatic stress disorder and a multi-modal approach to investigate psychiatric disorder development. We assessed trauma response and outcome through behavioral monitoring of freezing during the trauma itself and PTSD-like behavioral assessment after a prolonged period post-trauma respectively. The effect of trauma on neuroendocrine response was also measured in a subset of animals through corticosterone assay. To investigate neuroimaging biomarkers of susceptibility we measured pre-trauma brain-wide functional connectivity using awake rodent resting state functional magnetic resonance imaging. Through these methods we found that behavioral response during trauma was correlated with both the neuroendocrine response during trauma and the presentation of PTSD-like symptoms post-trauma. The freezing behavior during trauma was also correlated with the functional connectivity measures pre-trauma and revealed a subset of brain circuits that form a network framework of PTSD susceptibility. These results represent the importance of animal model studies of psychiatric disorders in their ability to differentiate biomarkers of susceptibility versus disorder through longitudinal assessment of disorder development.