<p>Recent interest in optimizing diagnostic thresholds for Post-traumatic Stress Disorder (PTSD) screening tools is motivated by the need to improve diagnostic accuracy and facilitate early treatment of PTSD within high-risk populations. However, existing approaches focus on diagnostic accuracy without considering the costs of screening and subsequent treatment, nor the impact of social stigma – which can undermine their effectiveness. We develop a modeling framework that captures the complex interplay between the screening selection rate, screening and treatment outcomes and costs, and the role of social stigma. Critically, our model incorporates feedback loops capturing how social stigma evolves in a vicious cycle wherein it inhibits effective screening and treatment, increasing the prevalence of severe cases of PTSD and future stigma. Our analytical study characterizes the model’s structural properties, including optimal screening selection rates and the long-term dynamics of stigma. Our numerical study, motivated by PTSD screening in the U.S. military, compares cost and stigma dynamics across various screening selection rates. Our results highlight the need to select screening thresholds that can balance the two objectives of lowering costs and social stigma in order to break the vicious cycle of stigma surrounding PTSD.</p>