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Compelling animal and human data indicate that stress compromises neurotrophic functions producing neural atrophy and reducing neuroplasticity resulting in dysfunction in brain circuitry associated with posttraumatic stress disorder (PTSD).This problem has been identified as the most important priority for studies of the neurobiology of PTSD.In the proposed symposium,we focus on recent developments in molecular imaging using positron emission tomography (PET) to close existing gaps between basic research in psychopathology,neurobiology and treatment with the ultimate goal to translate basic research into clinically relevant findings.To date,drug development in PTSD has been opportunistic,building almost solely on empirical observations with drugs approved for other indications.The next generation in PTSD drug development will focus on mechanism-based discovery and development,capitalizing on a burgeoning understanding of neural systems that mediate fear acquisition,consolidation,and extinction.State-of-the-art brain imaging using PET not only helps in the identification of novel targets for treatment development for PTSD,but also how PET imaging unravels mechanisms of resilience to the effects of traumatic stress which may inform novel treatment developments for patients with PTSD.Using novel radioligands for molecular targets,i.e.the serotonin 1B receptor or the norepinephrine transporter,we will present novel data unraveling molecular processes implicated in the human capacity to successfully adapt to extreme stress exposure.This symposium proposes that opportunities for new developments of prevention and treatment will occur through mechanism-based discovery,capitalizing on an increasing understanding of neural systems that mediate the psychiatric phenotype.