Development of an objective genomic biomarker-based screening tool for PTSD Background: Post-Traumatic Stress Disorder (PTSD) is a debilitating condition which affects US Service Members and Veterans disproportionately more often. Diagnosis is currently very subjective and referrals for definitive diagnosis and care are often based on responses to questionnaires. Delay in treatment often leads to maladaptive coping strategies, increased social dysfunction, decreased medical readiness.. The ability to develop a simple blood test based on biological markers of PTSD could revolutionize the care pathway by earlier diagnosis, decrease in stigma and the development of targeted novel therapeutics. Methods: Using a case control design, we compared the expression level changes as compared to baseline of patients with PTSD and patients without PTSD in order to find a pattern of expression that was predictive of PTSD. All patients had extensive evaluations by a trained psychiatrist as well as completing standardized self reporting tools for various mental health conditions. Blood samples were taken from each participant on the same day as the evaluation. Targeted RNA sequencing was carried out using the ADAPT Panel of 1003 genes involved in neuropsychiatric conditions and known related pathways. Findings: Using machine learning, we identified a pattern of gene expression across 21 genes that was predictive of PTSD. Measures of precision (Sensitivity, Specificity, and PPV) were better than the self reporting tools currently in use. Discussion: These findings are very promising for the development of an objective, blood based screening and/or diagnostic tool for PTSD; however larger training sets followed by clinical validation sets are needed to confirm these findings and control for co-morbid conditions such as alcohol use disorder, sleep disorders etc. Implications of this work: Diagnostic Precision: The use of RNA expression profiles as a biologic marker would increase the precision in a field where the current standard of subjective symptom based approach is limited by significant overlap in symptoms between conditions. Reduction of Stigma: A biologic biomarker for PTSD would establish a clear biologic basis for the symptoms the patient is experiencing and lessen the fear or perception that it is “all in their head”. Early Detection: The ability to screen objectively for PTSD objectively as we do for diabetes or thyroid will allow for earlier diagnosis and referral for treatment. Improved Treatment: Understanding of the biologic dysregulation underlying PTSD will allow for the development of targeted therapeutics. Conclusion: The discovery of an RNA expression profile exclusive to PTSD patients and its absence in healthy controls is a leap forward in the field of PTSD research. While further studies are needed to unravel the RNA profiles in PTSD's pathogenesis, severity and response to treatment, its presence provides a tangible biological anchor to a disorder often marred by its subjective diagnostic criteria. With continued research and exploration, we can disrupt the current symptom-based paradigm in mental health and bring precision to diagnostic tools and the development of novel treatment approaches rooted in molecular science.