Rapid eye movement sleep & extinction trial in post-traumatic stress disorder

This Randomized Controlled Trial (RCT) investigates whether the dual orexin receptor antagonist lemborexant increases rapid eye movement (REM) sleep and improves fear extinction recall compared to a placebo control. Participant with previous trauma exposure and PTSD will be recruited and randomly assigned to the double-blinded drug condition. The intervention group receives one dose of 10mg lemborexant orally about 1h before bedtime. On the test day, participants will complete a standardized and well-validated fear conditioning and extinction task which examines their capacity to acquire conditioned fear (via recording skin conductance response [SCR] reflecting physiological arousal to stimuli paired with a mild electric shock) and extinguishing fear. Prior to the task, the level of shock will be individually set at a level that is uncomfortable, but not painful. For the fear acquisition phase, they will look at visual images of a scene containing a desktop lamp which lights up with a color. One color will be associated with a mild electrical shock (the CS+), the other colored circle is never associated with shock (the CS-). This will be followed immediately by the fear extinction phase in which they will look at both colored lights which will never be followed by shock. This paradigm is adapted from Milad, Orr, Pitman, & Rauch (2005) and the approximate duration of the task is 20 minutes. SCR will be recorded to reflect sympathetic arousal. SCR amplitude typically increases to the CS+ compared to the CS- in the acquisition phase, and then gradually reduces over the extinction phase. The slope of decline of SCR over the fear extinction phase reflects how well an individual can inhibit/regulate their fear and reflects their capacity for fear extinction learning. Next, participants view emotive and neutral images selected from the International Affective Picture System (IAPS, task duration approximately 10 minutes). Then, participants will take the drug (oral tablet) under direct supervision by research staff and sleep at the lab while polysomnography (PSG) records sleep including REM sleep during the test night. This is followed by a recovery night at home to allow full drug washout (an ambulatory PSG records REM sleep during the recovery night). The participants return to the lab the next morning for the follow up. First they are asked to remember, recognized and rate the IAPS images they have seen two days before. Then, they complete the extinction phase again while SCR is recorded to measure recall of fear extinction. The extent that their fear returns reflects how well they remember the fear extinction from the first test day. The following week, participants record any intrusive memories that they have of the IAPS images.