REM Sleep, Safety Signal Learning, and Extinction Processes in PTSD

University Of California, San Diego, La Jolla CA

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Abstract

? DESCRIPTION (provided by applicant): Approximately 5.2 million adults suffer from posttraumatic stress disorder (PTSD) in a given year. PTSD is associated with a number of negative physical and mental health consequences. While evidence-based pharmacological and psychosocial interventions for PTSD have been developed within the last few decades, not all patients respond fully to treatment. Investigating the biological processes involved in the development and maintenance of PTSD as well as the mechanisms of treatment response will increase understanding of the disorder and aid in the development of effective interventions. Fear conditioning plays a crucial mechanistic role in PTSD, as patients with PTSD retain conditioned fear to cues associated with trauma long after the traumatic event has passed. Additionally, emerging evidence implicates deficits in safety learning in PTSD, as patients with PTSD are often unable to distinguish dangerous from safe environments. Extinction of conditioned fear is necessary for PTSD symptom reduction, either through the natural course of recovery or in response to exposure-based therapies for PTSD. In addition, it is crucial for patients to retain extinction over time as well as generalize extinction to a variety of settings ad cues in order to remain free of PTSD symptoms long-term. Our research group recently demonstrated an association between safety learning and Rapid Eye Movement (REM) sleep in healthy humans. The implications of this finding are particularly salient for patients with PTSD, because some of the most ubiquitous and distressing symptoms of PTSD are nightmares, which occur in REM sleep, and insomnia. Additionally, a growing body of research shows that sleep, particularly REM sleep, serves an important role in the acquisition, recall, and generalization of extinction memories in animal models and healthy humans. Nothing is known about the link between REM sleep and safety signal learning or extinction memory in clinical populations, though. This study will be the first to examine the relationship between safety signal learning, REM sleep, and extinction recall and generalization in PTSD patients. The specific aims of the proposal are: 1) determine if safety signal learning is related to subsequent REM sleep in patients with PTSD, and 2) determine if REM fragmentation is related to impaired a) extinction memory formation and b) extinction generalization, in patients with PTSD.