A Human Model That Suggests a Role for Sleep in the Cognitive Neuropsychology of PTSD and Recovery

IN THE LEAD ARTICLE OF THE CURRENT ISSUE OF SLEEP, PACE-SCHOTT AND COLLEAGUES UTILIZED AN EXPERIMENTAL PARADIGM TO EVALUATE THE role of sleep in the extinction of fear-conditioned memory.1 They tested “extinction recall” where a period of sleep versus an equivalent period of wake time followed the conditioning/extinction phase of the experiment. While not detecting an effect of sleep on the degree of extinction, they did find that the generalization of extinction from an extinguished stimulus to a similar stimulus that was presented in the conditioning but not during the extinction phase of the experiment, depended on sleep. While relationships between sleep and fear conditioning and extinction have been demonstrated in animal studies, this appears to be a unique demonstration in humans. Of further significance, commented on by the authors, is the relevance of their findings to the pathogenesis and cognitive-behavioral treatment of anxiety disorders. The model of fear conditioning and “failure of extinction” is highly salient to posttraumatic stress disorder (PTSD). Most individuals will have distressing images, waking thoughts, and related dreams for a period of time following stressful and threatening experiences. For people with PTSD, memories of being fired upon, seeing the mutilated body of a fellow combatant, or the brutality and threat of an assault can remain vivid or readily rekindled, and can be accompanied by automatic behavioral responses (such as a startle reaction) for decades after traumatic experiences. In addition to the face validity of the model of failed extinction, one study utilizing a laboratory paradigm demonstrated diminished extinction in a group with PTSD.2 Another study that evaluated police recruits, demonstrated reduced extinction prior to trauma exposure to be a predictor of developing PTSD.3 Sleep is frequently disrupted in the aftermath of a traumatic event.4 Recent research has provided some clarity regarding the contribution of sleep disturbances to the development and maintenance of PTSD, and the nature of sleep disturbances in the disorder. A recent meta-analysis of 20 polysomnographic studies indicates that patients with PTSD have been found to have lighter sleep (more stage 1, less stage 3) and elevated REM density compared to controls.5 Studies conducted by our group have documented an association of fragmented REM sleep with the development of PTSD during the early aftermath of trauma.6 Increased arousals and awakenings from REM sleep were reported in a study of a community recruited sample with current or past PTSD7 and a recent clinical study from Japan noted “REM interruption” in association with PTSD.8 However, too few studies had examined REM sleep disruption for it to have been detected in the meta-analysis. The significance of the REM sleep findings for PTSD likely relate to the dependence of emotional memory consolidation9 and contextual fear extinction in an animal model10 on REM sleep mentioned by Pace-Schott et al. In a recent report noting the enduring impact of sleep immediately following acquisition on consolidating emotional memory, Wagner et al.11 suggest that sleep deprivation directly after trauma might prevent PTSD. While this hypothesis is presently untested, implications of REM sleep learning findings for PTSD interventions need to consider that extinction is an active (and reversible) learning process12 as is the emotional processing that is thought to underlie therapeutic effects of psychological treatments for PTSD.13 Therefore, and in view of the findings of Pace-Schott et al., it is likely that intact sleep is important for emotional recovery from trauma or PTSD, at least beyond a short period when trauma memory is initially consolidated. There are a number of ways that the effects of sleep disruption on learning could be modeled to relate to PTSD and its treatment. Pace-Schott et al. specifically demonstrated the necessity of sleep for generalization from an extinguished stimulus to a similar un-extinguished stimulus. Over-generalization, e.g., experiencing all loud noises as alarming, all members of an ethnic group and gender of an assailant as threatening, has been identified as a cognitive distortion that underlies PTSD.13 Pace-Schott et al. discuss how generalization is also important for the success of exposure treatments. With regard to the treatment of PTSD or emotional recovery from trauma, generalization could be adaptive when positive and/or reassuring experiences lead to being less distressed by, more trusting of, and/or confident in another person, group, or situation. The findings of Pace-Schott and others from the growing and compelling literature on sleep, learning, and emotional processing raise many possibilities for modeling PTSD phenomena and for translation into interventions. An example from what has long been an elusive quest to find pharmacotherapies that reduce nightmare symptoms of PTSD is the growing evidence for the effectiveness of prazosin.14 This adrenergic antagonist has been shown to block disruption of REM sleep from noradrenergic stimulation in an animal model15 and to increase the amount of REM sleep and duration of REM periods in a PTSD trial.16 While the findings of Pace-Schott et al. and other sleep learning experiments raise many questions that are presently unanswered, they increase our confidence that a good night's sleep is beneficial to recovery from trauma and PTSD.