Wilfred R. Pigeon

Meta-Analysis of Sleep Disturbance and Suicidal Thoughts and Behaviors

OBJECTIVE The potential association of various sleep disturbances to suicidal thoughts and behaviors is the subject of several reviews. The current meta-analysis was conducted to estimate the size of the association generally as well as between more specific relationships. DATA SOURCES Electronic databases for years 1966-2011 were searched to identify candidate studies using PubMed search terms suicide and sleep or sleep initiation/maintenance disorders or dreams or nightmares or sleep disorders/psychology or sleep disorders/epidemiology as well as Ovid search terms suicide and sleep or insomnia or nightmares. The search was supplemented by cross-referencing from identified articles and reviews. STUDY SELECTION Original studies reporting both sleep disturbance and suicide outcomes were identified with 39 of 98 studies (40%) comprising 147,753 subjects selected for inclusion. DATA EXTRACTION Data were extracted by multiple independent observers and verified by a study author. The meta-analysis was performed using random-effects models. The size of associations was calculated for all types of sleep disturbances and suicide outcomes combined and for more specific categories including nightmares, insomnia, and insomnia subtypes and suicidal ideation, suicide attempts, and suicide. Moderator effects were evaluated. RESULTS Overall, sleep disturbance was significantly associated with an increased relative risk for suicidal ideation, suicide attempt, and suicide ranging from 1.95 (95% CI, 1.41-2.69) to a relative risk of 2.95 (95% CI, 2.48-3.50) in unadjusted studies. Associations were smaller, but remained highly significant among adjusted studies. Depression did not moderate the association between sleep and suicide variables. CONCLUSIONS This meta-analysis supports an association between sleep disturbance and suicidal thoughts and behaviors. Sleep disturbances in general, as well as insomnia and nightmares individually, appear to represent a risk factor for suicidal thoughts and behavior. This proposition is further bolstered by the result that depression did not show risk moderation.

The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain

STUDY OBJECTIVES To assess the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in patients with non-malignant chronic pain. METHODS Twenty-eight subjects with chronic neck and back pain were stratified according to gender, age, and ethnicity, then assigned to one of the two treatment groups: CBT-I or a contact control condition. INTERVENTION Eight weeks of CBT-I including sleep restriction, stimulus control, sleep hygiene, and one session of cognitive therapy devoted to catastrophic thoughts about the consequences of insomnia. MEASUREMENTS AND RESULTS Outcomes included sleep diary assessments of sleep continuity, pre-post measures of insomnia severity (ISI), pain (Multidimensional Pain Inventory), and mood (BDI and POMS). Subjects receiving CBT-I (n=19), as compared to control subjects (n=9), exhibited significant decreases in sleep latency, wake after sleep onset, number of awakenings, and significant increase in sleep efficiency. The diary findings were paralleled by significant changes in the ISI (p=0.05). Significant improvement (p=0.03) was found on the Interference Scale of the Multidimensional Pain Inventory. The groups did not significantly differ on mood measures or measures of pain severity. CONCLUSIONS CBT-I was successfully applied to patients experiencing chronic pain. Significant improvements were found in sleep as well as in the extent to which pain interfered with daily functioning. The observed effect sizes for the sleep outcomes appear comparable to or better than meta-analytic norms for subjects with Primary Insomnia.

Heart rate variability during sleep and the early development of posttraumatic stress disorder

BACKGROUND Noradrenergic function has been linked to posttraumatic stress disorder (PTSD) and might have a role in mediating sleep disturbances of the disorder. Our objective was to relate a peripheral manifestation of noradrenergic function, sympathetic nervous system activity as indexed by heart rate variability during sleep, to the development of PTSD in subjects with recent traumatic injuries. METHODS Subjects who had recall of life-threatening experiences were recruited from one of two regional trauma centers. Select subjects received a polysomnographic recording within 1 month of the trauma. Digitized electrocardiogram recordings were extracted from early and late rapid-eye-movement (REM) and preceding non-REM sleep periods. Autoregression was applied to R-R interval time series to calculate the ratios of low-frequency to high-frequency spectral densities (LF/HF ratios), which index sympathetic activation. Posttraumatic stress disorder status was determined at 2 months. RESULTS There was a significant state x group interaction: LF/HF ratios were higher during the REM sleep of the nine subjects who were positive for PTSD symptoms, compared with the 10 subjects who were PTSD negative. CONCLUSIONS Our findings are consistent with the possibility that increased noradrenergic activity during REM sleep contributes to the development of PTSD.

Chapter 60 – Etiology and Pathophysiology of Insomnia

Of all the sleep disorders, insomnia is perhaps the only one where there has been a substantial amount of top-down theorization. This may be the case because a framework is required to comprehend a disorder that has multiple causes and an insidious and progressive course. In this chapter, four general models of the etiology and pathophysiology of insomnia are summarized and critically evaluated. In particular, we review how each model characterizes the hyperarousal that is thought to be responsible for disturbing sleep continuity. Additional information is provided on how sleep homeostasis and circadian considerations may mediate, moderate, or interact with the hyperarousal. Insomnia is often considered a disorder of hyperarousal; that is, the patient has a level of arousal that is incompatible with the initiation or maintenance of sleep. The concept of hyperarousal is, however, likely to be quite complex. What is meant by arousal? How does it become elevated? Is hyperarousal a tonic phenomenon, and if not, what factors mediate or moderate its occurrence or intensity? Is arousal a singular construct, and are hyperarousal and sleep necessarily mutually exclusive? In this chapter, we review physiologic, cognitive, behavioral, and neurocognitive models of insomnia. Each of these will be summarized as it pertains to primary insomnia and sleep state misperception insomnia (paradoxical insomnia). These models may also be relevant to the extrinsic or secondary insomnias, which, when chronic, have a great deal in common with primary insomnia.1,2 In addition to reviewing the four models, we also summarize how sleep homeostasis and circadian considerations mediate, moderate, or interact with hyperarousal. Finally, we review a recent hypothesis that suggests that hyperarousal may be better conceptualized as a failure of wakefulness inhibition. PHYSIOLOGIC MODEL OF INSOMNIA The physiologic model suggests that chronic insomnia may be understood as a condition in which the patient has a trait level of arousal, or a level of arousal prior to or during the preferred sleep period, that is incompatible with good sleep continuity. This model assumes that physiologic arousal and sleep are mutually exclusive. Studies evaluating physiologic arousal in insomnia have used a variety of techniques, including basic psychophysiologic measures, whole-body metabolic rate, heart rate variability, caffeine-induced insomnia, neuroendocrine measures, and functional neuroimaging. The studies discussed next support the general concept of physiologic hyperarousal but have yet to be integrated into a formal model that explains how insomnia develops and how arousal effects promote sleeplessness (Fig. 60–1). Psychophysiolgic Measures of Arousal Early studies comparing elevated physiologic arousal between poor sleepers and good sleepers were based on electrophysiologic measures of heart rate, respiration rate, skin and core body temperature, muscle tone, skin conductance and resistance, and peripheral blood flow or vasoconstriction.3-8 Overall, these studies showed that poor sleepers exhibit increased physiologic arousal, and in the case of ECG measures of heart rate, this arousal was particularly evident at sleep onset. Several methodologic difficulties limit the interpretation of these studies. First, subjects in these investigations would not necessarily meet current definitions for primary insomnia, and the inclusion of subjects with other types of insomnia (e.g., sleep phase delay disorder or insomnia secondary to major depression) could have influenced the findings. Second, it is not clear whether these studies carefully excluded short episodes of sleep prior to consolidated sleep onset or short awakenings after sleep onset. The failure to do so could account for some of the sleep onset and nocturnal findings regarding hyperarousal. Third, most of the early studies did not distinguish between state and trait hyperarousal. This distinction is important in order to determine whether physiologic hyperarousal is a 24-hour phenomenon or whether it occurs only at night, only during the sleep period, or only in association with sleep-related stimuli. Of the early studies that provided data regarding this last issue, the results varied based on the measures and protocols adopted.6,7 When examining body temperature, Adam and colleagues found persistent effects across the day. 714 Figure 60–1. The physiologic model. THE PHYSIOLOGIC MODEL

Distinguishing between excessive daytime sleepiness and fatigue: toward improved detection and treatment.

INTRODUCTION Excessive daytime sleepiness (EDS) and fatigue occur in high percentages in the general population. They are common complaints in primary care and in specialty medicine. Although they may represent distinct or overlapping phenomena, the general medical literature does not normally distinguish between EDS and fatigue. Despite their prevalence, both EDS and fatigue are identified and treated in a relatively small proportion of those affected. The similarity of EDS and fatigue may create diagnostic ambiguity and thereby contribute to under-identification and under-treatment. Fatigue, in particular, is thought to be difficult to manage when it is identified. METHODS The literature was searched for reviews, meta-analysis and similar levels of papers focused on EDS or fatigue. RESULTS EDS and fatigue are operationalized in ways that contribute to blurring rather than to distinguishing between them. Existing measures of both EDS and fatigue may also contribute to their misidentification. Effective treatments for both symptoms have been established. Behavioral interventions are effective and underutilized. DISCUSSION We suggest more precise operationalization of EDS and fatigue, leading to a refinement of existing measures or development of new tools, a structured interview with fatigue and EDS sections in the clinical setting, and more consideration for behavioral interventions.

Sleep Disturbance Preceding Suicide Among Veterans

OBJECTIVES We examined the role of sleep disturbance in time to suicide since the last treatment visit among veterans receiving Veterans Health Administration (VHA) services. METHODS Among 423 veteran suicide decedents from 2 geographic areas, systematic chart reviews were conducted on the 381 (90.1%) who had a VHA visit in the last year of life. Veteran suicides with a documented sleep disturbance (45.4%) were compared with those without sleep disturbance (54.6%) on time to death since their last VHA visit using an accelerated failure time model. RESULTS Veterans with sleep disturbance died sooner after their last visit than did those without sleep disturbance, after we adjusted for the presence of mental health or substance use symptoms, age, and region. CONCLUSIONS Findings indicated that sleep disturbance was associated with time to suicide in this sample of veterans who died by suicide. The findings had implications for using the presence of sleep disturbance to detect near-term risk for suicide and suggested that sleep disturbance might provide an important intervention target for a subgroup of at-risk veterans.

Longitudinal relationships of insomnia, nightmares, and PTSD severity in recent combat veterans.

OBJECTIVE This observational, longitudinal study of veterans with recent combat exposure describes the prevalence, severity and associations of posttraumatic stress disorder (PTSD), insomnia, and nightmares over time. METHODS Eighty recent combat veterans recruited from Veterans Health Administration primary care settings met inclusion criteria including hazardous alcohol use and at least subthreshold PTSD. Insomnia status and nightmare status were assigned based on the Insomnia Severity Index total score and the PTSD Checklist nightmare item, respectively. Participants were re-assessed six months following their baseline assessment. Analyses of variance compared insomnia and nightmare groups on PTSD, depression, and alcohol use severity. Analyses of covariance (controlling for baseline differences) examined whether insomnia and/or nightmares were associated with the clinical course of PTSD. Persistence of conditions was also examined. RESULTS At baseline, 74% presented with insomnia and 61% endorsed distressing nightmares. Insomnia was associated with significantly higher PTSD and depression severity at both baseline and six months. The presence of nightmares was associated with significantly higher PTSD severity at both time points and with depression severity at baseline only. Despite decreases in PTSD and depression severity, insomnia severity was relatively unchanged after six months. The prevalence and severity of nightmare complaints diminished modestly over time. CONCLUSION Among this sample of recent combat veterans, insomnia and nightmares were each strongly associated with the severity of both PTSD and depressive symptoms. Over time, insomnia in particular did not appear to resolve spontaneously and was associated with ongoing PTSD. Addressing insomnia early, therefore, may be a strategy to alter the course of PTSD.

The hypocretin neurotransmission system in myotonic dystrophy type 1

Background: Patients with myotonic dystrophy type 1 (DM1) frequently have symptoms of excessive daytime sleepiness (EDS). Some patients with DM1 show sleep-onset REM, similar to that observed in narcolepsy. Narcolepsy is characterized by impaired hypocretin (Hcrt) neurotransmission. Objective: To test for dysregulation of Hcrt neurotransmission in a prospective cohort of patients with DM1. Methods: Hcrt levels in CSF were measured by radioimmunoassay. Sleep physiology was assessed by overnight polysomnography (PSG) and a multiple sleep latency test (MSLT). Splicing of Hcrt receptor 1 and 2 (HcrtR1 and HcrtR2) mRNA was examined in postmortem samples of temporal cortex. Results: Seventeen of 38 patients with DM1 reported symptoms of EDS. Among patients with DM1 with EDS who underwent PSG/MSLT, 7 of 13 showed reduced sleep latency, sleep-onset REM, or both. However, CSF Hcrt levels in DM1 (mean 277 pg/mL, n = 38) were not different from controls (mean 277 pg/mL, n = 33). Also, splicing of HcrtR1 and HcrtR2 mRNA in patients with DM1 was similar to controls. Conclusions: Excessive daytime sleepiness and dysregulation of REM sleep occur frequently in patients with myotonic dystrophy type 1 (DM1). However, the pathophysiologic basis is distinct from narcolepsy, as patients with DM1 do not have a consistent defect of Hcrt release or receptor splicing.

Comparative effectiveness of CBT interventions for co-morbid chronic pain & insomnia: a pilot study.

INTRODUCTION Chronic pain is difficult to treat and often precedes or exacerbates sleep disturbances such as insomnia. Insomnia, in turn, can amplify the pain experience. Both conditions are associated with inflammatory processes, which may be involved in the bi-directional relationship between pain and sleep. Cognitive behavioral therapy (CBT) for pain and CBT for insomnia are evidence based interventions for, respectively, chronic pain and insomnia. The study objectives were to determine the feasibility of combining CBT for pain and for insomnia and to assess the effects of the combined intervention and the stand alone interventions on pain, sleep, and mood outcomes compared to a control condition. METHODS Twenty-one adults with co-occurring chronic pain and chronic insomnia were randomized to either CBT for pain, CBT for insomnia, combined CBT for pain and insomnia, or a wait-list control condition. RESULTS The combined CBT intervention was feasible to deliver and produced significant improvements in sleep, disability from pain, depression and fatigue compared to the control condition. Overall, the combined intervention appeared to have a strong advantage over CBT for pain on most outcomes, modest advantage over both CBT for insomnia in reducing insomnia severity in chronic pain patients. DISCUSSION CBT for pain and CBT for insomnia may be combined with good results for patients with co-occurring chronic pain and insomnia.

The evidence base of sleep restriction therapy for treating insomnia disorder

Sleep restriction therapy is routinely used within cognitive behavioral therapy to treat chronic insomnia. However, the efficacy for sleep restriction therapy as a standalone intervention has yet to be comprehensively reviewed. This review evaluates the evidence for the use of sleep restriction therapy in the treatment of chronic insomnia. The literature was searched using web-based databases, finding 1344 studies. Twenty-one were accessed in full (1323 were deemed irrelevant to this review). Nine were considered relevant and evaluated in relation to study design using a standardized study checklist and levels of evidence. Four trials met adequate methodological strength to examine the efficacy of therapy for chronic insomnia. Weighted effect sizes for self-reported sleep diary measures of sleep onset latency, wake time after sleep onset, and sleep efficiency were moderate-to-large after therapy. Total sleep time indicated a small improvement. Standalone sleep restriction therapy is efficacious for the treatment of chronic insomnia for sleep diary continuity variables. Studies are insufficient to evaluate the full impact on objective sleep variables. Measures of daytime functioning in response to therapy are lacking. Variability in the sleep restriction therapy implementation methods precludes any strong conclusions regarding the true impact of therapy. A future research agenda is outlined.