Post-Traumatic Stress Disorder: Basic Science and Clinical Practice.

POSTTRAUMATIC STRESS DISORDER (PTSD) WAS FIRST INTRODUCED AS A PSYCHIATRIC DIAGNOSIS IN 1980, AS THE TOLL OF COMBAT TRAUMA ON VETERANS of the Vietnam War was being recognized. However, a careful observer of human behavior, the poet Homer, identified the cardinal symptoms in an epic tale of a much earlier war.1 The sleep field has been slow to appreciate the prominent place of sleep disturbances, insomnia as well as recurrent nightmares, in the presentation of PTSD. These problems, in a large cohort of veterans of the current wars in Iraq and Afghanistan, as well as in veterans of earlier wars and victims of man-made and natural disasters, can be refractory to available treatments. It is therefore most timely that the prominent sleep researcher Peter Shiromani has teamed up with highly regarded authorities in clinical aspects of PTSD and the basic science of fear and anxiety, Terence Keane and Joseph LeDoux, respectively, to produce a book that will have much to offer both clinicians and investigators in the field of sleep. For the Sleep readership Post-Traumatic Stress Disorder will be of particular importance for the sections on basic arousal mechanisms and treatment strategies, both with chapters by leaders in the sleep field. Shiromani and Blanco-Centurion hypothesize that arousal systems important during waking for the maintenance of vigilance in the face of stress may also produce abrupt awakenings from sleep and that overactivation of arousal neurons could contribute to the disruption of sleep in PTSD. They then provide a clear and comprehensive overview of the mechanisms of normal sleep-wake control that are likely to malfunction in PTSD. Carter and de Lecea make a compelling case for the involvement of the hypocretin system in the sleep discontinuity, as well as the waking symptoms, of PTSD. Berridge's review of normal and stress-activated locus coeruleus-noradrenergic function offers an elegant synthesis of a complex area and discusses how noradrenergic antagonists might act to moderate the symptoms of PTSD. Ultimately there will need to be an explanation of how alpha-1 antagonist treatment, an exciting recent development in managing the nightmare and other sleep disturbances in PTSD, might work, particularly as noradrenergic locus coeruleus neurons are known to be slowed during NREM sleep and nearly silent during REM sleep. Sanford's and Tang's chapter will be essential reading for those interested in modeling the sleep disturbances of PTSD in animals. These authors make two overarching points. Both are exemplified by their findings of sleep changes in response to stress in rodents: first, a long-lasting response to more than mild stress (as in humans with PTSD) must be distinguished from an acute, perhaps homeostatic, response to a mild stressor; and second, in agreement with Yehuda and LeDoux,2 responses to stress that only a subset of animals show may be most translatable to PTSD, a disorder that develops in only a minority of humans exposed to a potentially traumatic stressor. Raskind's review of pharmacotherapy for PTSD is up-to-date, and among the finest syntheses of this information that I have read. He provides very useful commentary that will surely help clinicians to choose appropriate medications for difficult-to-treat populations, and he makes clear what the clinical psychopharmacology research agenda of the next decade should encompass. I found very convincing and novel this author's emphasis on the importance of assessing the response of individual symptoms, as well as a sum of all symptoms, in determining the efficacy of a treatment intervention. Raskind offers as a cogent example the sleep disturbances in PTSD; the SSRIs and SNRIs are widely used for treating the PTSD symptom complex, with some evidence basis, but these medications seem to neither improve insomnia nor reduce recurrent nightmares. A related point is that the SSRIs could even be expected to exacerbate sleep difficulties in PTSD, as they are the class of medications most commonly associated with acute REM sleep without atonia and REM sleep behavior disorder and patients with PTSD can display heightened motor activation during REM sleep.3,4 The contributions to Post-Traumatic Stress Disorder, with few exceptions, take the form of comprehensive reviews of the existing literature. Thus, it is surprising that the two chapters on psychotherapy for PTSD focus on two rather novel techniques, guided imagery and virtual reality exposure therapy (VRET), which may hold great promise but are not currently widely accepted treatment modalities. Rizzo et al. do describe prolonged exposure (PE), the only treatment for PTSD judged in a recent Institute of Medicine report to have a sufficient evidence basis, but this is primarily in the service of introducing VRET, which they argue may be more acceptable to veterans of the ongoing wars in Iraq and Afghanistan, men and women who may be reluctant to seek treatment for mental health problems with traditional “talk therapy.” A discussion of cognitive-processing therapy, which the Veterans Health Administration is now making available for the treatment of PTSD in veterans, would have been a useful addition.5 There are many other excellent chapters, authored by recognized experts, in this volume. Readers with a particular interest in sleep will, in several cases, have their appetite whetted for more information at the interface of PTSD and sleep. For example, Verfaellie and Vasterling provide a scholarly discussion of memory changes (during waking) in PTSD; yet for this reviewer they beg the question of how memory difficulties in PTSD may relate to recurrent nightmares, one way of remembering a traumatic event, during sleep. Others, familiar with the burgeoning literature on the role of sleep in memory consolidation, may wonder about a causal relationship between sleep disturbances and memory problems in PTSD. Liberzon's and Garfinkel's authoritative review of functional neuroimaging (during waking) in PTSD can serve as a reminder of the importance, as the technology advances, of imaging PTSD during sleep, when so much of the pathophysiology of the disorder is manifested. Post-Traumatic Stress Disorder should be seen as a landmark in the joining of the PTSD and sleep fields. That PTSD can only be fully understood and optimally treated in the context of sleep biology and sleep medicine will be recognized by researchers and clinicians alike. Learning how basic sleep mechanisms go awry in PTSD will in turn yield important insights into the functions of normal sleep.