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

Abstract

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, although this can increase to 25% among groups who have experienced severe psychological trauma, such as combat veterans, refugees and victims of assault. The risk of developing PTSD in the aftermath of severe trauma is determined by multiple factors, including genetics — at least 30–40% of the risk of PTSD is heritable — and past history, for example, prior adult and childhood trauma. Many of the primary symptoms of PTSD, including hyperarousal and sleep dysregulation, are increasingly understood through translational neuroscience. In addition, a large amount of evidence suggests that PTSD can be viewed, at least in part, as a disorder that involves dysregulation of normal fear processes. The neural circuitry underlying fear and threat-related behaviour and learning in mammals, including the amygdala–hippocampus–medial prefrontal cortex circuit, is among the most well-understood in behavioural neuroscience. 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, mechanistic knowledge of fear circuitry, transformational advances in the conceptual framework, diagnosis and treatment of PTSD are possible. In this Review, we describe the clinical features and current treatments for PTSD, examine the neurobiology of symptom domains, highlight genomic advances and discuss translational approaches to understanding mechanisms and identifying new treatments and interventions for this devastating syndrome. Post-traumatic stress disorder (PTSD) is one of the few neuropsychiatric disorders for which the timing and cause of onset are understood, facilitating research into the underlying mechanisms. In this Review, Ressler and colleagues examine the neurobiology of PTSD, highlighting new insights from omics studies and discussing future directions of research. Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder, characterized by re-experiencing, avoidance, negative emotions and thoughts, and hyperarousal. PTSD is frequently comorbid with neurological conditions such as traumatic brain injury, post-traumatic epilepsy and chronic headaches. PTSD has a prevalence of approximately 6–8% in the general population and up to 25% among individuals who have experienced severe trauma. Many of the neural circuit mechanisms that underlie the PTSD symptoms of fear-related and threat-related behaviour, hyperarousal and sleep dysregulation are becoming increasingly clear. Key brain regions involved in PTSD include the amygdala–hippocampus–prefrontal cortex circuit, which is among the most well-understood networks in behavioural neuroscience. Combining molecular–genetic approaches with a mechanistic knowledge of fear circuitry will enable transformational advances in the conceptual framework, diagnosis and treatment of PTSD. Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder, characterized by re-experiencing, avoidance, negative emotions and thoughts, and hyperarousal. PTSD is frequently comorbid with neurological conditions such as traumatic brain injury, post-traumatic epilepsy and chronic headaches. PTSD has a prevalence of approximately 6–8% in the general population and up to 25% among individuals who have experienced severe trauma. Many of the neural circuit mechanisms that underlie the PTSD symptoms of fear-related and threat-related behaviour, hyperarousal and sleep dysregulation are becoming increasingly clear. Key brain regions involved in PTSD include the amygdala–hippocampus–prefrontal cortex circuit, which is among the most well-understood networks in behavioural neuroscience. Combining molecular–genetic approaches with a mechanistic knowledge of fear circuitry will enable transformational advances in the conceptual framework, diagnosis and treatment of PTSD.