Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Post-traumatic stress disorder (PTSD) is a maladaptive and debilitating psychiatric disorder characterized by re-experiencing, avoidance, negative emotions and thoughts, and hyperarousal in the months and years following exposure to severe trauma. PTSD has a prevalence of approximately 6–8% in the general population. However, this can increase to 25% among groups who have experienced severe psychological trauma, such as combat veterans, refugees and victims of assault. Multiple factors, including genetics, determine the risk of developing PTSD in the aftermath of severe trauma — at least 30–40% of the risk of PTSD is heritable — and history, for example, prior adult and childhood trauma. Furthermore, the study of threat-responding and its underlying circuitry has led to rapid progress in understanding learning and memory processes. By combining molecular–genetic approaches with a translational, mechanical knowledge of fear circuitry, transformational advances in the conceptual framework, diagnosis and treatment of PTSD are possible. In this Review, the study describes the clinical features and current treatments for PTSD, examines the neurobiology of symptom domains, highlights genomic advances, and discusses translational approaches to understanding mechanisms and identifying new therapies and interventions for this devastating syndrome.