Learning, memory and brain plasticity in posttraumatic stress disorder: context matters.

We review evidence from our laboratory that suggests that in addition to enhanced cue conditioning and delayed cue extinction disturbed contextual learning may play an important role in the development and maintenance of posttraumatic stress disorder. Based on data from a longitudinal sample of rescue workers at high risk for posttraumatic stress disorder and data on single trauma exposed persons with and without posttraumatic stress disorder we show the crucial role of the hippocampus for contextual memory and impaired contextual learning along with enhanced cue conditioning and delayed extinction in PTSD. Using structural and functional magnetic resonance imaging we confirmed animal data on the role of the hippocampus in contextual and the importance of the amygdala in cue conditioning and the role of the frontal cortex in extinction. Genetic variants related to the modulation of the hypothalamus-pituitary-adrenal axis are associated with cue and genetic variants related to calcium signaling and memory processes and the regulation of the stress response are associated with context conditioning. These genes also play a role in PTSD. Further research needs to identify the predictive nature of these learning processes and plastic brain changes and their interaction with genetic characteristics changes for the transition into PTSD and its maintenance. A further focus needs to be on the identification of learning and memory mechanisms and the associated brain plasticity across disorders.