Sleep disturbances and post-traumatic stress disorder; a perpetual circle?

Background: Sleep facilitates the consolidation of fear extinction memory. Disrupted sleep has been proposed as a vulnerability factor for the development of posttraumatic stress disorder (PTSD). Moreover, nightmares and insomnia are hallmark symptoms of PTSD, possibly interfering with fear extinction and compromising recovery. A perpetual circle may develop when sleep increases the risk for PTSD, and PTSD leads to an increase of sleep disturbances. To date, therapeutic options for alleviating sleep disturbances in PTSD are limited. Methods: We conducted two studies to examine the relationship between sleep and post-traumatic symptoms; 1. in 453 Dutch service members the impact of pre-deployment insomnia symptoms and nightmares on the development of PTSD symptoms at 6 months was assessed, 2. veterans with PTSD (n=13), veterans without PTSD (n=17) and healthy controls (n=15) slept in a sleep laboratory with an IV catheter out of which blood was sampled from 2200h to 0800h. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) were determined in conjunction with polysomnographic registrations, subjective sleep parameters and a declarative memory task before sleep. Memory consolidation was assessed the next morning. Also the relationship between obstructive sleep apnea syndrome (OSAS) and PTSD symptoms was examined. In addition to these studies, we systematically reviewed the literature on treatment options for sleep disturbances, and we conducted a randomized controlled trial (RCT) (n=14) comparing prazosin and placebo. Results: Pre-deployment nightmares predicted PTSD symptoms at 6 months post-deployment, however insomnia symptoms did not. Furthermore, a correlation between the apnea index and PTSD severity was observed, while OSAS was not more prevalent in patients with PTSD. We observed a significant increase in awakenings during sleep in PTSD, which were positively correlated with ACTH levels, and negatively correlated with GH secretion, and the subjective perception of sleep depth. Also, heart rate (HR) was significantly increased in PTSD patients. Interestingly, plasma levels of GH during the night were significantly decreased in PTSD. Furthermore, GH secretion and awakenings were independent predictors for delayed recall, which was lower in PTSD. Only a few RCTs have been published. They show promising results for olanzapine, and the 1-adrenoceptor antagonist prazosin. In our RCT prazosin was not associated with improvement of subjective and objective sleep parameters. However due to small sample sizes, the power to detect treatment-related differences was limited. Conclusions: Disturbed sleep due to nightmares increases the risk for PTSD. PTSD in turn leads to increased sleep fragmentation, decreased GH secretion and frequent nightmares, which may again compromise fear extinction, synaptic plasticity and recovery. This suggests that disturbed sleep is a precipitating and perpetuating factor in PTSD symptomatology, creating a perpetual circle. Both the activity of the hypothalamo-pituitary adrenal (HPA) axis and the sympathetic nervous system (SNS) may be involved in disturbed sleep in patients with PTSD. RCTs indicate that inhibiting noradrenergic activity with prazosin during sleep has a positive effect on nightmare complaints, while polysomnographic measures of sleep do not seem to be affected