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Psychobiologic Mechanisms of Posttraumatic Stress Disorder

Dennis S. Charney, MD; Ariel Y. Deutch, PhD; John H. Krystal, MD; Steven M. Southwick, MD; Michael Davis, PhD
Arch Gen Psychiatry. 1993;50(4):294-305. doi:10.1001/archpsyc.1993.01820160064008.
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Posttraumatic stress disorder (PTSD) is an illness of considerable prevalence, often characterized by high morbidity, treatment resistance, and a chronic course. The core symptoms of PTSD include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and autonomic hyperarousal. We propose several neurobiologic mechanisms that may account for these primary symptoms of PTSD. Preclinical investigations of the effects of stress on learning and memory processes suggest that fear conditioning, behavioral sensitization, and a failure of extinction may be important in the persistence and reexperiencing of traumatic memories and stressor sensitivity. The pathophysiology of PTSD may involve dysfunction of several brain structures, particularly the amygdala, locus coeruleus, and hippocampus, as well as noradrenergic, dopamine, opiate, and corticotropinreleasing factor neurochemical systems. Acutely, severe psychological trauma results in the parallel activation of these systems, producing an array of adaptive behavioral and physiologic responses necessary for survival. In PTSD, however,

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