Vermetten E, Lanius RA.
Handb Clin Neurol. 2012;106:291-342.

Abstract
Three decades of posttraumatic stress disorder (PTSD) research have placed it well on the map. PTSD is a young disorder that started being properly understood only from 1980 with incorporation in DSM-III, in which it was acknowledged that exposure to traumatic events can lead to long-term psychopathology. This chapter reviews the history and nosology of the disorder, epidemiology, and etiology, as well as the clinical features. It lists the diagnostic assessments and provides an overview of the biological framework of the disorder by addressing brain, neurohormonal, and transmitter alterations. Exposure to traumatic events is commonplace. The majority of exposed subjects are resilient, as this is still the rule rather than the exception.The reported prevalence of PTSD is twice as common in females compared to males. The A criterion in PTSD expressed the traumatic event, after which the symptom clusters are based on intrusions, avoidance, and irritability. Gene-environmental studies are needed, with a focus on specific, distinct endophenotypes and influences from environmental factors (e.g., traumatic early-life experiences, with abuse or neglect, as well as exposure to disasters or combat). PTSD is often accompanied by comorbid disorders, such as depression and other anxiety disorders, as well as drug and alcohol abuse and dependence. The disorder is heterogeneous, sometimes with complex features that focus on emotional dysregulation, attachment, and dissociation. Several validated trauma assessments are available that allow quantification of trauma symptomatology. The biological framework is based on the concepts of stress sensitization and fear conditioning as well as failure of inhibition. After the decade of the hippocampus we have seen a shift to the decade of the amygdala in the new millennium. Given the specific role of the prefrontal cortex in (neuro)psychological functions in patients with PTSD (i.e., attention and cognitive interference), interest in the role of the prefrontal cortex will increase significantly. Increased multidisciplinary involvement, with inclusion of genetics, endocrinology, immunology, (neuro)psychology, and psychopathology, is essential to find consistency between biological, emotional, and cognitive dysfunction in PTSD. A variety of effective psychological and pharmacological interventions can be used to treat PTSD. The mechanisms of exposure therapy and cognitive therapy in influencing neurobiological markers need to be further investigated. The same goes for emerging therapies such as eye movement desensitization and reprocessing, virtual reality exposure, internet therapy, and neurofeedback. There are no specific drugs for PTSD, except for the treatment of irritability and depressive features with selective serotonin reuptake inhibitors. Other options, such as specific serotonergic agents, e.g., 5-HT(1A) antagonists, norepinephrine blockers, corticotropin-releasing factor antagonists, glucocorticoid receptor antagonists, prazosin and a(1)-adrenergic blocker with nightmares, and use of beta-blockers early after trauma exposure, are investigated. New treatment options such as d-cycloserine and cortisol seem to offer opportunities to influence memory consolidation of traumatic experiences in timed relation to exposure. For health economy it is important to be aware that there is an economic burden associated with PTSD, and treatments require the use of scarce resources. They will ultimately provide tools to ascertain the relative efficiency of different treatment options and plan the availability of these for the affected population. This can be seen as the biggest challenge for the future evolution of the disorder.