Showing papers in "Sleep in 2010"

Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies

Abstract: Background: Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes. Objectives: To assess whether the population longitudinal evidence supports the presence of a relationship between duration of sleep and all-cause mortality, to investigate both short and long sleep duration and to obtain an estimate of the risk. Methods: We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. We included studies if they were prospective, had follow-up >3 years, had duration of sleep at baseline, and all-cause mortality prospectively. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. We carried out sensitivity analyses and assessed heterogeneity and publication bias. Results: Overall, the 16 studies analyzed provided 27 independent cohort samples. They included 1,382,999 male and female participants (follow-up range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P <0.01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; [1.22 to 1.38]; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001). Conclusion: Both short and long duration of sleep are significant predictors of death in prospective population studies.

Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments.

Abstract: Study Objectives: To develop an archive of self-report questions assessing sleep disturbance and sleep-related impairments (SRI), to develop item banks from this archive, and to validate and calibrate the item banks using classic validation techniques and item response theory analyses in a sample of clinical and community participants

Surgical Modifications of the Upper Airway for Obstructive Sleep Apnea in Adults: A Systematic Review and Meta-Analysis

Abstract: A substantial portion of patients with obstructive sleep apnea (OSA) seek alternatives to positive airway pressure (PAP), the usual first-line treatment for the disorder. One option is upper airway surgery. As an adjunct to the American Academy of Sleep Medicine (AASM) Standards of Practice paper, we conducted a systematic review and meta-analysis of literature reporting outcomes following various upper airway surgeries for the treatment of OSA in adults, including maxillomandibular advancement (MMA), pharyngeal surgeries such as uvulopharyngopalatoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP), and radiofrequency ablation (RFA), as well as multi-level and multi-phased procedures. We found that the published literature is comprised primarily of case series, with few controlled trials and varying approaches to pre-operative evaluation and post-operative follow-up. We include surgical morbidity and adverse events where reported but these were not systematically analyzed. Utilizing the ratio of means method, we used the change in the apnea-hypopnea index (AHI) as the primary measure of efficacy. Substantial and consistent reductions in the AHI were observed following MMA; adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent; adverse events were reported more commonly. Papers describing positive outcomes associated with newer pharyngeal techniques and multi-level procedures performed in small samples of patients appear promising. Further research is needed to better clarify patient selection, as well as efficacy and safety of upper airway surgery in those with OSA.

Insomnia with Short Sleep Duration and Mortality: The Penn State Cohort

Abstract: Study Objectives: Because insomnia with objective short sleep duration is associated with increased morbidity, we examined the effects of this insomnia subtype on all-cause mortality.

Trends in the prevalence of short sleepers in the USA: 1975-2006.

Abstract: Study Objectives: To determine (1) whether short sleep has increased over 31 years; (2) whether trends in short sleep differed by employment status; (3) which sociodemographic factors predict short sleep; and (4) how short sleepers spend their time.

Sleep duration and cardiovascular disease: results from the National Health Interview Survey.

Abstract: CARDIOVASCULAR DISEASE (CVD) IS THE LEADING CAUSE OF MORTALITY IN THE UNITED STATES AND ELSEWHERE.1 RECENT STUDIES SUGGEST THAT sleep disorders adversely affect cardiovascular health.2 In the National Health Interview Survey (NHIS) 2004-2007, more than one-third of the population in the US were reported to have an abnormal sleep duration, defined as either a short or long sleep duration.3 Several studies have shown that compared to 7-8 hours of sleep, both shorter and longer sleep durations are associated with CVD risk factors such as diabetes,4,5 hypertension,6 and obesity.7 However, previous studies8–13 that examined the association between sleep duration and CVD showed inconsistent associations. This included studies that reported an association with CVD for short sleep duration only,13 or long sleep duration only,9,11,14 or both short and long sleep durations.8,10,12 Three previous studies have examined the association between sleep duration and CVD in the US.8,9,14 The Nurses' Health Study8 and the Women's Health Initiative Observational Study14 reported positive associations between sleep duration and coronary heart disease (CHD) in women. The First National Health and Nutrition Examination Survey (NHANES-1) Follow-up Study reported a positive association between sleep duration and stroke in a nationally representative cohort of 7,844 men and women; however no significant association was found between sleep duration and CHD.9 Accumulating evidence have shown that depression is related to both sleep duration15 and CVD risk.16 However, most of the studies8–10,13 that assessed the association between sleep duration and CVD have not adjusted for depression, potentially an important confounder in the association between sleep duration and CVD. In this context, we examined the association between sleep duration and CVD, including CHD and stroke in the NHIS 2005, a large, nationally representative sample of US adults after controlling for the effect of depression and other confounders.

Fatigue in Multiple Sclerosis: Mechanisms, Evaluation, and Treatment

Abstract: Among patients with multiple sclerosis (MS), fatigue is the most commonly reported symptom, and one of the most debilitating. Despite its high prevalence and significant impact, fatigue is still poorly understood and often under-emphasized because of its complexity and subjective nature. In recent years, an abundance of literature from specialists in sleep medicine, neurology, psychiatry, psychology, physical medicine and rehabilitation, and radiology have shed light on the potential causes, impact, and treatment of MS-related fatigue. Though such a diversity of contributions clearly has advantages, few recent articles have attempted to synthesize this literature, and existing overviews have focused primarily on potential causes of fatigue rather than clinical evaluation or treatment. The aims of this review are to examine, in particular for sleep specialists, the most commonly proposed primary and secondary mechanisms of fatigue in MS, tools for assessment of fatigue in this setting, and available treatment approaches to a most common and challenging problem.

Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort.

Abstract: Study Objectives: To investigate the relationship between sleep duration and insomnia severity and the risk of all-cause death and cardiovascular disease (CVD) events

Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults.

Abstract: Background: Practice parameters for the treatment of obstructive sleep apnea syndrome (OSAS) in adults by surgical modification of the upper airway were first published in 1996 by the American Academy of Sleep Medicine (formerly ASDA). The following practice parameters update the previous practice parameters. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine.

Sleep deprivation impairs the accurate recognition of human emotions.

Abstract: Study Objectives: Investigate the impact of sleep deprivation on the ability to recognize the intensity of human facial emotions.

The Association of Sleep Duration with Adolescents' Fat and Carbohydrate Consumption

Abstract: OVER THE PAST 40 YEARS, INSUFFICIENT SLEEP DURATION AMONG ADOLESCENTS HAS MARKEDLY INCREASED, WHEREBY TODAY ONLY ABOUT 33% OF teens are getting the recommended 9 hours of sleep.1 Concurrent with this rise in short sleep duration is the epidemic of obesity.2 Obesity in children and adolescents is a growing health concern because of its adverse impact on metabolism, blood pressure, respiratory disease, and quality of life,3 as well as its association with adult obesity and chronic illnesses, including cardiovascular diseases, cancer, musculoskeletal disease, and gastrointestinal disease.4,5,6 A number of studies have suggested that there is a link between sleep loss and weight gain in adults.7–9 For children, this finding has been consistent across large samples studied in various countries10,11 and in prospective studies.12 Studies with older children or adolescents have found the relationship between short sleep duration and obesity for males but not for females.13–15 Physiologic studies have shown that sleep deprivation may influence weight through effects on appetite, physical activity, and/or thermoregulation.16,17 Experimental reductions in sleep duration have been hypothesized to alter metabolic rate or to affect the levels of appetite regulatory hormones, leptin and ghrelin.16–21 An association between insufficient sleep and increased caloric intake has been demonstrated in some,22 but not other,23 studies. Differences in the literature may relate to differences in experiment design. Understanding the association between insufficient sleep and obesity in the population has been limited by a paucity of research that has quantified both energy intake and sleep duration in individuals studied in their native environments. Thus, it is unclear whether the mechanisms that mediate sleep loss and energy balance are through appetitive pathways, changes in energy expenditure, or altered metabolism. In this study, we examined the association between weekday sleep duration and energy consumption in adolescents aged 16 to 19 years studied in their natural environment. Using rigorously collected multiple-pass 24-hour food recalls and objectively measured sleep duration from wrist actigraphy, we tested the hypothesis that shorter sleep is associated with altered nutrient intake, including altered proportions of caloric intake from fats, carbohydrates, and snacks.

Continuous Positive Airway Pressure Reduces Risk of Motor Vehicle Crash among Drivers with Obstructive Sleep Apnea: Systematic Review and Meta-analysis

Abstract: Context: Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle crash.

Neurobehavioral Dynamics Following Chronic Sleep Restriction: Dose-Response Effects of One Night for Recovery

Abstract: RECOVERY OF NEUROBEHAVIORAL FUNCTIONS FROM CHRONIC CURTAILMENT OF SLEEP DURATION AS A RESULT OF WORK, MEDICAL CONDITIONS, OR lifestyle1 is not well understood. It has been rarely studied, despite the fact that a common sleep pattern for millions of people involves sleep restriction for 5 weekdays/workdays, followed by sleep extension on at least one weekend night (or day off from work).2–4 Much of what is known about recovery from sleep loss has been based on total sleep deprivation experiments, where robust NREM EEG slow wave activity (SWA, 0.5-4.5Hz) responses are the norm.5–9 Experiments in chronically sleep-restricted rats revealed increased recovery sleep duration, NREM and REM sleep durations, and elevated SWA, while only a small portion of the chronically lost sleep was actually recovered.10,11 Experiments in healthy humans have confirmed that chronic reduction of sleep can result in waking neurobehavioral deficits that become progressively worse over days;12–15 that the rate of accumulation of waking deficits is a function of the magnitude of the sleep restriction;12,15,16 and that measures of sleepiness, performance lapsing, and cognitive slowing can accumulate to deficit levels found for total sleep deprivation.15 These findings indicate that waking brain impairment from chronic sleep loss is sleep dose-dependent, that it can be as severe as that resulting from total sleep deprivation, and that the “sleep debt” is a result of prior sleep-wake history extending back in time more than a day. Thus, chronic sleep restriction appears to induce slow changes (spanning days to weeks) in neural processes mediating alertness, attention and other aspects of cognitive functioning, including learning and memory.17 How these slow (cumulative) changes are reversed via the dynamics of recovery sleep is not known. Kleitman suggested “sleep debts” are “liquidated” by extending recovery sleep duration (p. 317).18 However, the primary model of human sleep homeostasis, the two-process model,19,20 posits that the intensity and temporal dynamics of NREM EEG SWA, more so than sleep duration, reflect the recovery process. For example, the two-process model predicts only an initial modest (∼10%-20%) elevation in SWA over the first few days of sleep restricted to 4 h per night, which has been experimentally confirmed,15,21 although increases of 50% have been reported for a broader EEG frequency band (1.25-7.75 Hz).22 The relatively modest increment in SWA during and following sleep restriction is not congruent with the large cumulative neurobehavioral deficits that develop across days of sleep restriction.15 The apparent uncoupling during chronic sleep restriction of the putative marker of homeostatic sleep drive (SWA) and waking neurobehavioral functions suggests that sleep duration and/or other aspects of sleep (e.g., REM sleep) may also have a critical role in recovery of neurobehavioral capability following chronic sleep restriction. On the other hand, the high degree of colinearity among SWA, TST and the duration of sleep stages may prevent attributing recovery from chronic sleep restriction to a specific physiological feature of sleep. The dynamics of recovery of human waking alertness and neurobehavioral functions following chronic sleep restriction have not been systematically investigated. Experiments in healthy adults scheduled to 7 nights of sleep restricted to 3 h-7 h TIB12 or 5 nights of sleep restricted to 4 h TIB22 yielded data suggesting that some neurobehavioral functions may not return to baseline following up to 3 recovery sleep periods limited to 8 h TIB.12,23 Studying the dynamics of recovery from cumulative sleep loss is critical to a range of behavioral guidelines (e.g., days off duty for recovery from work schedules),24 biological questions (e.g., mechanisms and rates of homeostatic sleep drive build-up and dissipation),25 and theoretical issues (e.g., processes to instantiate into mathematical models predicting sleep and alertness).26–28The present experiment was designed to provide the first systematic, randomized, sleep dose-response data on the dynamic recovery of neurobehavioral functions when a single recovery sleep opportunity follows 5 days of nocturnal sleep restriction to 4 h TIB. The study tested the hypothesis that following sleep restriction, recovery of primary measures of neurobehavioral alertness would increase monotonically in relation to the duration of time allowed for recovery sleep. We also sought to determine the features of sleep that parallel this recovery.

Effects of sleep deprivation on dissociated components of executive functioning.

Abstract: SLEEP LOSS IS A GROWING THREAT TO SAFETY IN MODERN SOCIETIES, AS BOTH WORK HOURS AND COMMUTE TIMES ARE EXTENDED.1 SLEEP LOSS impairs performance on simple cognitive tasks such as signal detection and reaction time (RT) tests.2 Many occupational settings, however, require executive functioning—the ability to initiate, monitor, and stop actions so as to achieve goals3—in order to execute complex tasks such as interpersonal communication, creative problem solving, and decision making.4 Thus, an important question is to what extent executive functions are impaired by sleep loss.5 The real-world relevance of this question is illustrated by occupational disasters including the nuclear meltdown of Chernobyl, the grounding of the Exxon Valdez, and the disastrous launch decision of the Challenger space shuttle, all of which involved complex decision errors for which sleep loss has been cited to be a contributing factor. Several studies have examined deficits in executive functioning during sleep deprivation.6–20 Between studies there has been considerable inconsistency as to whether and how executive functions were found to be impaired.21 For example, two recent studies found that sleep deprivation impaired performance on a go/no-go task,8,9 which is typically considered to measure the ability to inhibit a prepotent response. Another study, using Stroop task performance as an index of ability to inhibit a prepotent response, reported that this executive function was not impaired during sleep deprivation.19 Similarly, one study reported that sleep deprivation changed behavioral decisions involving risk on a lottery choice task,16 while another study using a different gambling task observed no significant differences in choices made after sleep loss.20 Inconsistencies like these have made it difficult to derive a uniform account of whether and how sleep deprivation affects executive functions. Horne and colleagues12 have posited that sleep deprivation especially impairs performance on tasks tapping executive functions because these tasks selectively rely on the prefrontal cortex. A basis for this theory is provided by EEG-based and neuroimaging evidence that sleep loss affects the frontal lobes more than most other brain areas. For instance, studies have shown that sleep pressure, as operationalized by increased theta power density in the waking EEG, is most evident in frontal areas during total sleep deprivation (TSD).22,23 Using PET neuroimaging, which allows greater anatomical specificity, it has been documented that TSD decreases metabolism specifically in the prefrontal cortex.24 From findings like these it has been inferred that sleep loss would impair executive functioning and performance on tasks that rely on prefrontal cortical function more than non-executive task performance. In this vein, a parallel between the cognitive impairments seen in sleep deprivation and those seen in aging has been hypothesized,12 as both conditions seem to selectively involve reduced activity in the prefrontal cortex. There is ample evidence, however, that sleep deprivation also impairs performance on cognitive tasks requiring relatively little executive control.25 This includes the psychomotor vigilance test (PVT), a simple RT task measuring sustained attention.26 Based in part on detailed analyses of RT data from the PVT, Dinges and colleagues postulated that performance impairment during sleep deprivation is caused by an increase in moment-to-moment variability of attention resulting from the interaction of the homeostatic drive for sleep, the circadian drive for wakefulness, and compensatory effort to perform.27 They hypothesized that the variability in performance due to difficulty sustaining attention would transfer to a wide variety of cognitive tasks since “attention is a requirement of many goal-directed activities.”27 According to this “state instability” theory, sleep deprivation does not necessarily cause impairments in executive functions tasks because of selective deficits in the prefrontal cortex, but at least in part due to deficits in the ability to sustain attention. The theory implies that through impairment of sustained attention, sleep deprivation affects cognitive performance globally, including not only executive functioning and other higher order cognitive processes, but many other aspects of performance as well. One reason that different views exist as to how and why executive functioning may be degraded during sleep deprivation is that the tasks commonly used to measure executive functions do not allow dissociation of the various cognitive processes contributing to performance. By definition, executive functions operate on other cognitive processes, and any task that targets executive functions therefore also implicates non-executive cognitive processes (i.e., the task impurity problem).3 As such, a low score on an executive functions test does not necessarily arise from impairment of the target executive functions; it could also result from impairment of other component cognitive processes involved in the task.28 In the present laboratory study, we investigated sleep-deprived performance on an executive functions battery. The tasks in the battery were selected because they allow for the dissociation of some of the intertwined components of cognitive performance. Our battery made it possible to isolate 2 specific executive function components: working memory scanning efficiency, and suppression of irrelevant information that leads to proactive interference (that is, inhibition of information that is no longer relevant). Both of these executive function components involve the prefrontal cortex.29,30 They are associated with working memory capacity, and are fundamentally important to executive control during complex task performance.28 We investigated the extent to which working memory scanning efficiency, resistance to proactive interference, and other elements of task performance are affected by acute TSD.

Sleep Patterns Before, During, and After Deployment to Iraq and Afghanistan

Abstract: ACCORDING TO A 2008 REPORT FROM THE NATIONAL SLEEP FOUNDATION, AMERICANS ARE WORKING MORE AND SLEEPING LESS, WITH THE AVERAGE work day lasting 9 hours 28 minutes and time in bed only 6 hours 55 minutes.1 The US military is at particularly high risk for sleep disturbances due to hazardous working conditions, inconsistent work hours, harsh environments, routine exposure to loud noises, and crowded sleeping spaces.2,3 Exposures to these adverse working conditions are often intensified during deployments, including the current increased operational tempo, with lengthy and frequent deployments, as well as demanding training exercises. Deployment-related factors may lead to sleep complaints, including circadian desynchronosis, total or partial sleep deprivation, lengthy sleep latency, and wakening after sleep onset that may, in turn, exacerbate mental and physical health symptoms following deployment.2,3 The quantity and quality of sleep affect many aspects of physical and mental health.4–12 Military personnel deployed in support of Operation Iraqi Freedom and Operation Enduring Freedom may be at increased risk for chronic sleep loss, as well as many other adverse physical and mental conditions, compared with nondeployed military personnel.13–15 Sleep deprivation has been studied extensively and is associated with many physical and psychological effects, including increased risk-taking behavior,7,11 decreased threat detection,10 impaired decision making,7,11,12 performance degradation,4,8,9 mood disturbances,8 and tunnel vision.6 Short sleep duration has also been associated with obesity, weight gain, and heart disease.5,16,17 A recent cross-sectional study of 156 deployed US Air Force Airmen found that 40% of respondents suffered from at least 1 sleep disturbance, and 75% of respondents reported diminished sleep quality while deployed when compared to sleep quality at home.3 The purpose of this study was to determine any association between deployment in support of the operations in Iraq and Afghanistan and sleep quantity and quality in a large military population. We hypothesized that military personnel who had deployed would have more trouble sleeping and sleep less than those who have not deployed. The Millennium Cohort Study18 includes all Service branches of the US military, active-duty, Reserve, and National Guard personnel. A substantial proportion (22%) of cohort members were deployed in support of the operations in Iraq and Afghanistan between baseline and follow-up surveys. This population provided valuable information on sleep patterns, as well as behavioral, occupational, and demographic characteristics among participants who completed their survey during and after deployment.

Earlier Parental Set Bedtimes as a Protective Factor Against Depression and Suicidal Ideation

Abstract: Study Objectives: To examine the relationships between parental set bedtimes, sleep duration, and depression as a quasi-experiment to explore the potentially bidirectional relationship between short sleep duration and depression. Short sleep duration has been shown to precede depression, but this could be explained as a prodromal symptom of depression. Depression in an adolescent can affect his/her chosen bedtime, but it is less likely to affect a parent's chosen set bedtime which can establish a relatively stable upper limit that can directly affect sleep duration.

The prevalence of short sleep duration by industry and occupation in the National Health Interview Survey.

Abstract: THE NATIONAL SLEEP FOUNDATION (NSF) RECOMMENDS THAT HEALTHY ADULTS SLEEP 7-9 H/DAY; BUT EPIDEMIOLOGICAL STUDIES SUGGEST THAT mean sleep duration among American adults has decreased substantially over time, with an increased percentage of adults who report an average sleep duration of ≤ 6 h/day1,2 Recent surveys indicate that American workers average 67 to 76 h of sleep per workday3,4 Both short and long habitual sleep time have been found to be associated with increased risks of mortality,5,6 hypertension,7,8 coronary heart disease,9 and diabetes10 In addition, short sleep duration has been found to be associated with self-rated poor health11 and elevated body mass index (BMI)12 Among workers, insufficient sleep can affect job performance and workplace safety, which are important occupational health considerations13–15 In addition to understanding the effects of sleep duration, it is important to study determinants that predict or influence an individual's sleep duration16 This issue is important because: 1) understanding the primary determinants of sleep duration will allow for the design of studies that can appropriately control for confounders and effect modifiers; and 2) knowledge of the determinants of sleep duration will allow for identification of subgroups at highest risk for sleep related morbidity, so that these subgroups can be targeted with appropriate interventions Non-occupational factors that have been associated with short sleep duration include demographic factors: being male,17–20 being non-Hispanic black,18,21 being divorced or widowed,18,19 low levels of education,7,18,19 and urban residence18 Some studies have found a U-shaped relationship between age and short sleep duration, with lower prevalence of short sleep duration among young adults and older adults, compared to middle-aged adults2,17; while other studies have suggested a more linear increase in prevalence of short sleep duration with age7 High self-reported stress,18 smoking,18,20,22,23 activity limitations and leisure-time physical inactivity,18,23 and alcohol consumption18,22,23 have also been associated with short sleep duration Employed persons tend to have a higher prevalence of short sleep duration than unemployed persons18; and, with regard to work schedules, early morning start times,24 rotating shifts,25 night shifts,26 and long work hours17 are associated with short sleep duration

Association of short sleep duration with weight gain and obesity at 1-year follow-up: a large-scale prospective study.

Abstract: Study Objectives: To investigate the association between short sleep duration and elevated body mass index (BMI) and obesity in a large sample of Japanese adults over a short period

Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea.

Abstract: OBSTRUCTIVE SLEEP APNEA (OSA) IS A COMMON DISORDER IN WHICH RECURRENT SLEEP RELATED UPPER AIRWAY OBSTRUCTION CAUSES SLEEP fragmentation and intermittent hypoxemia. Ethnicity has been suggested as an important risk factor for OSA. However, defining the role of ethnicity is complex, as it incorporates genetic, environmental, and cultural factors that can, individually or in combination, influence the other recognized risk factors for OSA. Whilst earlier prevalence studies suggest that OSA may be more common in certain ethnic groups,1,2 recent data in Hong Kong Chinese,3 Indians4 and Koreans5 suggest that OSA prevalence in these ethnic groups are not dissimilar to the Caucasian populations.6 Obesity and craniofacial factors are well recognized in the pathogenesis of OSA. It is also becoming clear that the balance and interaction between these two risk factors is crucial in the development of OSA.7,8 It is likely that such interaction is strongly influenced by ethnicity. Cephalometric studies have suggested that craniofacial factors are important determinants of OSA risk in Asian cohorts.9–11 Similarly, studies evaluating the role of obesity suggest that whilst it is a consistent risk factor for OSA across ethnic groups, the risk attributable to obesity differs between racial groups.3,6 Despite suffering from a similar degree of OSA, patients from Asian groups are generally less overweight compared to their Caucasian counterparts, suggesting that ethnicity may differentially influence the attribution of these OSA risk factors. To date, studies that have explored these complex interactions remain limited, especially in a direct inter-ethnic comparison. Hence the aim of this study was to explore the differences in craniofacial structures and obesity between Caucasian and Chinese patients with OSA.

The Effect of Short Sleep Duration on Coronary Heart Disease Risk is Greatest Among Those with Sleep Disturbance: A Prospective Study from the Whitehall II Cohort

Abstract: STUDY OBJECTIVES: Short sleep duration is associated with increased CHD (coronary heart disease) mortality and morbidity, although some evidence suggests that sleep disturbance is just as important. We investigated whether a combination of short sleep duration and sleep disturbance is associated with a higher risk of CHD than their additive effects. SETTING: The Whitehall II study. PATIENTS OR PARTICIPANTS: The Whitehall II study recruited 10,308 participants from 20 civil service departments in London, England. Participants were between the ages of 35 and 55 years at baseline (1985-1988) and were followed up for an average of 15 years. INTERVENTIONS: N/A. MEASUREMENTS: Sleep hours and sleep disturbance (from the General Heath Questionnaire-30) were obtained from the baseline survey. CHD events included fatal CHD deaths or incident nonfatal myocardial infarction or angina (ICD-9 codes 410-414 or ICD-10 120-25). RESULTS: Short sleep duration and sleep disturbance were both associated with increased hazards for CHD in women as well as in men, although, after we adjusted for confounders, only those reporting sleep disturbance had a raised risk. There was some evidence for an interaction between sleep duration and sleep disturbance. Participants with short sleep duration and restless disturbed nights had the highest hazard ratios (HR) of CHD (relative risk:1.55, 95% confidence interval:1.33-1.81). Among participants who did not report any sleep disturbance, there was little evidence that short sleep hours increased CHD risk. CONCLUSION: The effect of short sleep (< or = 6 hours) on increasing CHD risk is greatest among those who reported some sleep disturbance. However, among participants who did not report any sleep disturbance, there was little evidence that short sleep hours increased CHD risk.

Sleep Symptoms Predict the Development of the Metabolic Syndrome

Abstract: THE CLUSTERING OF CARDIOVASCULAR RISK FACTORS KNOWN AS THE METABOLIC SYNDROME IS STRONGLY AND PROSPECTIVELY LINKED WITH incident cardiovascular events, diabetes, and mortality.1 Given that prevalence rates of the metabolic syndrome are estimated at 20% in the adult population,2 identifying modifiable risk factors associated with the development of the metabolic syndrome is of critical public health importance. Several prospective studies have documented an independent relationship between sleep disturbances, including sleep disordered breathing (SDB) and sleep duration, and increased risk of developing individual components of the metabolic syndrome, including obesity, hypertension, glucose intolerance, and diabetes.3–8 Additionally, a handful of cross-sectional studies have shown that a broader range of self-reported sleep disturbances, including snoring, sleep duration, difficulty initiating and maintaining sleep, and poor sleep quality, as well as polysomnographically assessed sleep architecture are associated with prevalent metabolic syndrome.9–13 However, to our knowledge, no study to date has prospectively examined the relationship between sleep disturbances that commonly present in clinical practice and the development of the metabolic syndrome. Given evidence that there may be added prognostic value of the metabolic syndrome, over and above its individual components, and the inability of cross-sectional studies to support the proposed direction of causality between sleep disturbances and metabolic dysregulation, prospective evidence is clearly needed to examine whether sleep disturbances predict the development of the metabolic syndrome. Most epidemiologic studies of sleep and CVD risk have examined sleep symptoms rather than sleep disorders identified by diagnostic criteria, such as insomnia or obstructive sleep apnea syndrome (OSAS), which are the two most common adult sleep disorders.14 Understanding the relative impact of sleep symptoms versus sleep disorders may have important public health implications given that symptoms are much more prevalent than disorders,14 and the putative mechanisms linking sleep with cardiometabolic consequences may differ for symptoms and disorders. Moreover, there is considerable overlap in SDB and insomnia symptoms. Thus, to better understand the pathophysiology underlying links between sleep symptoms and cardiometabolic risk, it is critical to examine the independent effects of respective insomnia and SDB symptoms as well as more formally defined disorders. The present study investigated the degree to which insomnia or SDB predicted the development of the metabolic syndrome and its component factors (hyperglycemia, central adiposity, hypertension, hypertriglyceridemia, and low high density lipoprotein cholesterol) over a 3-year period in a community sample. We used two different case definitions for both insomnia and SDB. For insomnia, we examined individual insomnia symptoms as well as insomnia syndrome, which included a sleep complaint along with reported daytime impairment. For SDB, we examined whether snoring, the most common symptom of OSA, predicted the development of the metabolic syndrome, independent of apnea-hypopnea index, a physiological indicator of OSA. Given racial and gender differences in the prevalence of sleep disorders and the metabolic syndrome, for significant effects, we explored whether relationships between sleep symptoms and the metabolic syndrome differed among men and women and among blacks and whites.

Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study.

Abstract: INSOMNIA IS THE MOST COMMON SLEEP DISORDER, YET LITTLE IS KNOWN ABOUT THE MECHANISMS, CAUSES, CLINICAL COURSE, AND CONSEQUENCES of this highly prevalent chronic condition.1 Many studies have established that insomnia is highly comorbid with psychiatric disorders and is a risk factor for the development of depression, anxiety, and suicide.2 However, the evidence on the association of insomnia with medical morbidity is very limited.1,2 Although insomniacs commonly complain of cognitive deficits, mainly of attention and concentration, there is a surprising lack of evidence to suggest a link between chronic insomnia and cognitive dysfunction in objective testing.3–5 In fact, published reviews demonstrated poorer performance among patients with insomnia in only a small number of studies (approximately 10% to 25%), according to the 2006 Standards in Insomnia Committee. Thus they concluded that no specific psychomotor or cognitive-performance measure can be recommended for routine use in insomnia studies.6 In the 3 most recent studies,7–9 using polysomnography and performance data to compare insomniacs to normal sleepers, results were mixed. Two of 3 studies included only small sample sizes, whereas the third included a relatively large group of research volunteer primary insomniacs and used a rather narrowly focused battery. To date, our sample is the largest population-based study using full polysomnography and a comprehensive neuropsychological battery that has been conducted in adults to investigate the association of insomnia and performance. We have previously reported that objective short sleep duration in insomnia may be an index of the biological severity of the disorder. Specifically, insomnia with short sleep duration has been shown to be associated with a high risk for hypertension10 and type 2 diabetes11 as well as with activation of the hypothalamic-pituitary-adrenal (HPA) axis.12–14 The latter finding is particularly relevant to neuropsychological performance because hyperactivity of the HPA axis has been shown to be associated with neurocognitive deficits.15–18 Based on these observations, we speculate that insomniacs with short sleep duration may be at high risk for deficits in neuropsychological performance. In order to test this hypothesis, we examined the joint effects of the complaint of chronic insomnia and objective sleep duration on the neuropsychological performance of a large cross-sectional population-based sample from The Penn State Cohort.

Sleep Disturbance Immediately Prior to Trauma Predicts Subsequent Psychiatric Disorder

Abstract: THERE IS CONVERGENT EVIDENCE THAT LIFETIME HISTORY OF INSOMNIA IS A RISK FACTOR FOR SUBSEQUENT PSYCHIATRIC DISORDER. STUDIES OF adults have repeatedly found that sleep disturbance is associated with greater risk for development of depression1–5 and anxiety1,3 in adults. There is also evidence that sleep problems in children or adolescents is predictive of subsequent mental health problems.6 One possible reason for the relationship between sleep disturbance and subsequent psychiatric disorder is that impaired sleep may limit one's capacity to manage stressors that precipitate psychiatric disorder. Impaired sleep disturbance prior to a stressor may contribute to subsequent disorder because it (a) limits the cognitive resources available to manage the stress, (b) contributes to hyperarousal that may lead to psychiatric disorder, (c) represents an additional stressor that compounds the effect of the environmental stressor, or (d) limits restorative sleep that is required to manage stressful events. To date, no studies have directly examined the influence of sleep disturbance immediately prior to experiencing a marked stressor on development of subsequent psychiatric disorder. Previous epidemiological studies have typically studied the onset of chronic sleep disturbance prior to the onset of psychiatric disorder; however, this approach does not allow specification of the sleep disturbance immediately prior to a stressor that may precipitate psychiatric disorder. One small study reported that sleep disturbance prior to Hurricane Andrew was associated with increased risk of disorder following the trauma.7 This study's conclusions were limited, however, by obtaining reports of pre-trauma sleep functioning 6 months after the hurricane. The current study aims to test the proposal that sleep disturbance immediately prior to traumatic stressor increases the risk of subsequent psychiatric disorder. This large longitudinal study of survivors of traumatic injury was conducted across 4 hospital sites and assessed sleep disturbance in the 2 weeks prior to the traumatic injury. Participants were re-assessed 3 months later to determine the relationship between sleep disturbance and development of a range of psychiatric disorders. We predicted that patients with sleep disturbance immediately prior to the traumatic injury would be more likely to develop posttraumatic psychiatric disorders. On the basis of convergent evidence that sleep disturbance is prevalent in many psychiatric disorders,8 it is important to ensure that the effect of sleep disturbance is not a proxy for the influence of prior psychiatric disturbance immediately prior to the trauma. Accordingly, this study assessed for lifetime psychiatric disorders, and controlled for prior disorder.

The Use of Exogenous Melatonin in Delayed Sleep Phase Disorder: A Meta-analysis

Abstract: Study Objectives: To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder.

Age-related reduction in daytime sleep propensity and nocturnal slow wave sleep.

Abstract: EPIDEMIOLOGICAL STUDIES HAVE DOCUMENTED AN INCREASED PREVALENCE OF SLEEP COMPLAINTS, INCLUDING INSOMNIA, IN OLDER ADULTS.1,2 The rate of prescriptions for hypnotics is high for this segment of the population although the effectiveness of current hypnotics remains unsatisfactory.3 Whether and how the age-dependent increase in insomnia is related to the age-related changes in sleep regulation in healthy individuals is currently not known. Healthy aging is associated with profound changes in sleep but there is no consensus on the interpretation of these changes in the context of models of sleep regulation and the consequences of these changes in nocturnal sleep for daytime function have not been established. Sleep complaints frequently mentioned in relation to aging are sleep interruptions, early morning awakening, and difficulty falling asleep.4 These changes in nocturnal sleep are thought to be related to the complaints of waking-not-refreshed, daytime napping and sleepiness.1,5 This linkage between nocturnal and diurnal complaints is supported by the widespread view of sleep as a recovery process in which the increase in sleep interruptions and the loss of deep sleep with age are viewed as indicators of less recuperative or insufficient sleep. The question of whether these age-related changes in sleep and daytime sleepiness are secondary to poor health and sleep disorders or are also observed in healthy aging has received some attention.6 One common answer is that aging in healthy people is not necessarily associated with poor sleep and that sleep need is not reduced in old age,7 but experimental evidence in favor or against this view is rather limited. Physiological studies of sleep have also documented marked changes in sleep structure in healthy older people. Key changes include a striking age-related reduction in slow wave sleep (SWS) and computer detected slow wave activity (SWA), as well as reductions in sleep continuity and sleep maintenance parameters.8,9 Reductions in REM sleep and total sleep time (TST) are also observed with aging, although these changes are less striking.10 These age-related changes in physiological sleep parameters are nearly continuous across the adult lifespan but the time course of changes differs between the various sleep parameters.8,10 Changes in sleep structure, sleep continuity, sleep maintenance, and early morning awakening can be interpreted within the framework of the homeostatic and circadian regulation of sleep.11–13 In this widely accepted conceptualization of sleep regulation, SWS/SWA is considered a principle marker of the homeostatic process, whereas sleep continuity, maintenance, and early morning awakening are determined by the interaction of the circadian and homeostatic processes. Several experimental approaches have attempted to identify the relative contribution of these 2 processes, and their interaction with the age-related changes in sleep.14,15 Sleep deprivation and sleep satiation experiments have probed sleep homeostasis in older adults. Circadian phase shifting through scheduled light exposure experiments have quantified the contribution of circadian phase. Forced desynchrony experiments investigated the interaction of the circadian and sleep process. Key findings that are consistent across these protocols are: (1) the homeostatic and circadian regulation of sleep operates in old age; and (2) age-related changes in SWS and sleep continuity/duration persist across all circadian phases. One overarching interpretation of these findings is that the age-related reduction in SWS sleep reflects a reduction in homeostatic sleep drive/need. According to this interpretation, the reduced sleep continuity and maintenance, early morning awakening, and increased susceptibility to circadian phase misalignment and other internal and external stimuli are secondary to the reduction in homeostatic sleep drive and the depth of sleep. An alternative interpretation is that the changes in SWS and sleep continuity primarily reflect sleep that is less efficient in dissipating sleep pressure without an underlying reduction in homeostatic sleep drive or sleep requirement. When sleep is seen as a restorative process, these 2 interpretations lead to opposite predictions with respect to daytime consequences—such as sleepiness— of the age-related nocturnal sleep changes. The interpretation that aging is associated with a reduced homeostatic sleep drive predicts age-related reductions or no change in daytime sleep propensity, provided that sleep opportunity does not change with age. In contrast, when the age-related changes in sleep are seen as an indication of sleep being less efficient in dissipating sleep pressure or insufficient, a build up of homeostatic sleep pressure is predicted. This should lead to excessive daytime sleepiness in older people, if not pathological sleepiness seen in clinical examples of disrupted sleep such as in sleep apnea.16 Insufficient sleep resulting in a build-up of homeostatic sleep pressure without changing total sleep duration can be modelled by experimental disruption of SWS. In SWS deprivation experiments, in which subjects are prevented from entering deep sleep by administration of acoustic stimuli contingent upon the ongoing EEG, a homeostatically regulated rebound of SWS occurs.17–19 This rebound is observed within a sleep episode if the SWS disruption takes place at the beginning of the sleep episode. The rebound is observed during the subsequent sleep episode when the sleep disruption is continued to the end of the nocturnal sleep episode.20 This implies that the SWS deficit is carried over an intervening wake episode and that homeostatic sleep pressure is higher during wake episodes following SWS disruption. The daytime consequences of either age-related changes in sleep or experimental disturbances of SWS and sleep continuity, however, have not been studied extensively. One early study, in which daytime sleep propensity was assessed using the multiple sleep latency test (MSLT), it was found that older people were sleepier,21,16 or at least as sleepy as young people.22 Subsequent studies have largely confirmed these findings although in some it was noticed that older people may be as sleepy or less sleepy than young people.6,23 Studies of the effects of aging on daytime functioning, including sleepiness, varied considerably in their control of sleep-wake history and the extent of the general health and sleep screening and nocturnal sleep structure and continuity were not always quantified. Therefore, firm conclusions on the relationship between daytime sleep propensity and aging can currently not be drawn. The association between SWS and sleep continuity and daytime sleep propensity has not been firmly established in healthy individuals, and it is not known whether this relationship changes with age. Descriptive studies in patient populations have provided some evidence for a role of sleep continuity and SWS in the regulation of daytime sleep propensity.24 Small-scale experimental studies of SWS disturbances and associated changes in sleep continuity have been shown to affect daytime sleep propensity in healthy individuals,25–27 but whether these effects are of a similar magnitude in all age-groups is not currently known. In order to better understand the nature of the age-related changes in sleep and daytime sleep propensity and to investigate the role of SWS sleep and sleep continuity in the regulation of daytime sleep propensity, we conducted a large-scale experiment in which sleep and daytime sleep propensity was quantified under baseline conditions as well as during and after experimental disruption of SWS. The experimental disruption of SWS allowed for the assessment of responsiveness of daytime sleep propensity to insufficient sleep. The experiment was conducted in carefully screened healthy young, middle-aged, and older individuals, all of whom were scheduled to an 8-h sleep opportunity for at least 5 nights prior to the 4-day laboratory experiment. The data demonstrate that, whereas experimental disturbances of SWS lead to increased daytime sleep propensity in all age groups, at baseline aging is associated with a reduction of daytime sleep propensity, despite reductions in nocturnal SWS and sleep continuity.

Functional neuroimaging insights into the physiology of human sleep.

Abstract: Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep. Citation: Dang-Vu TT; Schabus M; Desseilles M; Sterpenich V; Bonjean M; Maquet P. Functional neuroimaging insights into the physiology of human sleep. SLEEP 2010;33(12):1589-1603.

Post-H1N1 narcolepsy-cataplexy.

Abstract: NARCOLEPSY-CATAPLEXY, A DISEASE CAUSED BY THE LOSS OF ∼70,000 HYPOCRETIN CELLS IN THE HYPOTHALAMUS AFFECTS ∼20 PER 100,000 INDIVIDUALS, with an incidence of ∼ 0.3–0.6 per 100,000 person-years.1,2 Onset is most typically in the teens, and cases with onset before age 6 or after 40 are rare in Western Europe and North America.3 The disease is extremely tightly associated with human leukocyte antigen (HLA) DQB1*06024, so that DQB1*0602 negative cases without documented loss of hypocretin cells, as measured by cerebrospinal fluid (CSF) hypocretin levels, are exceptional; only 5 such cases have been reported in the literature. The cause of narcolepsy is likely autoimmune based on the HLA association, association with T-cell receptor polymorphisms,5 and recently reported Tribbles 2 autoantibodies.6 As for most autoimmune diseases, twin pairs are most often discordant (65% to 80%), and environmental triggers are suspected to play a critical role.1 Most notably, two recent reports have found an association with past streptococcus infections,7,8 leading to the speculation that upper airway infections could be involved in many cases as a cofactor. The possibility that narcolepsy could be a rare side effect of H1N1 flu vaccination was first reported by the Swedish Medical Product agency in August 2010 (6 cases). Additional cases (up to 14) were also reported in Finland, potentially linked to Pandemrix vaccination, an H1N1 vaccination formulation containing the adjuvant ASO3. Vaccination has been suspended in these countries.9 In three major centers of reference for narcolepsy—Montpellier, France; Montreal, Canada; and Stanford University, United States—we noticed in the first months of 2010 an unusual increase in abrupt onset narcolepsy-cataplexy diagnosed within a few months of H1N1 onset. These observations were made independently and first discussed among directors of the 3 centers at a sleep meeting in spring 2010, prior to any media attention. From September 2008 to August 2009, 9 recent-onset cases (symptoms of less than one year duration before being diagnosed) were identified in the 3 centers. The following year (September 2009–August 2010), 31 recent onset cases were identified (8 cases in Montpellier, 9 in Montreal, 14 at Stanford). These cases were examined for past H1N1 exposure or vaccination by review of clinical charts, and when possible additional interviews by phone or in person. Of the 31 cases, 14 post-vaccination cases were identified at Montpellier (n = 6), Montreal (n = 4), and Stanford University (2 of 4 US cases were vaccinated in Europe). In addition, 2 cases following H1N1 infection (as opposed to vaccination) were also reported at Stanford. These patients were interviewed to specify the date of cataplexy onset. Information regarding date of vaccination and type of vaccine was also obtained in all cases. Multiple sleep latency tests (MSLTs) were performed in all cases older than 9 years old. Serum, CSF, and DNA were collected for biochemical measurements. Serum samples were tested for the presence of antistreptolysin O (ASO).7 The presence of anti-TRIB2 antibodies was tested in Lausanne, Switzerland, for the 6 French cases6 or at Stanford, USA, for the remaining cases.10 DNA was tested for the presence of DQB1*0602. CSF hypocretin-1 levels were measured as previously described.11 A summary description of the 16 post-H1N1 cases is reported in Table 1. All cases were HLA DQB1*0602 positive with severe sleepiness and definite/severe cataplexy. All were Caucasian except case 3 (African American), and 50% were male. In 10 cases, CSF hypocretin-1 was found to be extremely low ( 200 pg/mL). MSLTs were performed in 11 cases, with confirmation of diagnosis in all cases, i.e., mean sleep latency < 8 minutes and ≥ 2 SOREMPs. The post streptococcal marker ASO was positive in 11 cases (68.7%), confirming a previous report in recent-onset cases.7 None of our post-H1N1 subjects were anti-TRIB2 positive, in contrast to recent-onset cases collected in prior years.6,10,12 Brain MRI (performed in 6 cases) were unremarkable except for the presence of a pineal cyst in 2 cases. The most striking features of our sample were the abrupt onset and the unusual severity of both sleepiness and cataplexy. Rapid weight gain was frequently noted, as is typical with abrupt onset cases. Finally, we noted that age at onset was often atypical, with 5 cases with onset after age 38, and 2 with very early onset (under 5 years of age from the United States). Of the 14 post-vaccination cases, 11 cases followed adjuvanated vaccination, while 3 were vaccinated without adjuvant. Delay between vaccination and cataplexy onset in these cases ranged from 2 days (strong local response followed by a generalized reaction following vaccination) to 5 months, although in 9 of the 14 post-vaccination cases the onset occurred 2–8 weeks following vaccination. As the delay between onset and diagnosis is often long,1,13 more cases are likely to be identified in the future. Table 1 Characteristics of post H1N1 narcolepsy patients How could H1N1 vaccination or infection trigger narcolepsy? Possible hypotheses include a specific immune response to H1N1 (and possibly subsequent molecular mimicry) or generalized stimulation of the immune system. In Europe and Canada, as well as the cases reported in Scandinavia, most cases followed vaccination with ASO3. This vaccine has been reported to be associated with side effects suggestive of stronger immune stimulation.14 In the United States, where vaccination did not contain the ASO3 adjuvant, only 2 post-vaccination cases were documented. The strength of the immune response (higher with adjuvant, or after actual infections), rather than the specificity of the immune response to H1N1, may thus be involved. Several of our patients showed high ASO titers, suggesting that they had recent or recurrent streptococcus infections. An association between streptococcal infection and recent-onset narcolepsy was reported previously, in the absence of H1N1 vaccination. One possibility is that streptococcus infection could also act as a nonspecific immune trigger, for example via superantigen stimulation of dormant autoreactive T-cell clones. It is possible that these factors increase brain inflammation or blood brain penetration nonspecifically, allowing the autoimmune process to reach hypocretin cells. Fever and the administration of various adjuvants have been reported to increase blood brain penetration and activate brain microglia in animal models.15 Cases reported here with their temporal link between vaccination and disease onset and unusual clinical presentation, with rapid development and severity of both excessive daytime somnolence and cataplexy, suggest that H1N1 vaccination or exposure may trigger narcolepsy. However, there are several limitations and potential confounding factors, such as increased awareness of narcolepsy and more efficient diagnostic processes leading to faster diagnosis and increased identification of recent-onset cases. Another limitation is that a large portion of the population was either vaccinated or had H1N1 infection, including many unrecognized instances of infection, increasing the difficulty to document a specific association between narcolepsy onset and H1N1 infection or vaccination. Nevertheless, these correlative findings indicate an urgent need for further examination of a possible link. Even if confirmed, as for other better-established post-vaccination autoimmune reactions such as Guillain-Barree, post-flu vaccination narcolepsy is likely to be an exceptionally rare complication.16–18 To our knowledge, vaccination has not previously been reported as a triggering factor for narcolepsy. The consequences of withholding vaccination should be weighed against the risk of potentially lethal H1N1 infections (that may also trigger narcolepsy based on our data). Considering that all cases reported here were HLA DQB1*0602 positive, HLA typing prior to vaccination could be considered in the future and would represent the first vaccinogenomic intervention.

Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent Health.

Abstract: ATHEROSCLEROSIS IS A DISEASE PROCESS RECOGNIZED TO BEGIN IN THE FIRST DECADES OF LIFE.1 IDENTIFICATION AND MANAGEMENT OF RISK factors for atherosclerosis can decrease the morbidity and mortality from the disease. Evidence from both experimental and population-based studies have implicated short sleep duration in the pathogenesis of obesity,2,3 diabetes,4,5 and hypertension,6,7 all of which are potent risk factors for atherosclerosis. There is growing evidence that short sleep duration may also play a role in the etiology of another primary risk factor for atherosclerosis, high cholesterol. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in postmenopausal women treated with hormone replacement therapy.8 Cross-sectional associations have been found between short sleep durations and lower HDL cholesterol levels in adult American women with type 2 diabetes9 and in adult Japanese women from the general population.10 Short sleep durations were found to be associated with the highest total cholesterol levels among all sleep duration categories in cross-sectional analyses that included both men and women from Norwegian11 and Korean12 adult populations. A number of mechanisms could mediate the relationship between inadequate sleep and hypercholesterolemia. First, sleep restriction has been shown to increase appetite by decreasing leptin and increasing ghrelin levels.2 Increased appetite could raise body weight and increase dietary intake of cholesterol, trans-fats, and saturated fats. Second, inadequate sleep is associated with daytime fatigue, which could lessen one's resolve to engage in physical activity. Physical activity has been shown to lower LDL and raise HDL levels.13 Third, inadequate sleep could increase stress. Acute stress has been shown to significantly increase total and LDL cholesterol levels,14 and acute stress responsivity has been shown to predict clinically elevated cholesterol levels and LDL cholesterol levels 3 years later.15 Stress has been theorized to increase blood lipids through catecholamine-induced lipolysis and the release of free fatty acids that serve as substrate for triglyceride resynthesis and hepatic VLDL production.14 We are not aware of any previous population-based studies on the relationship between sleep duration and high cholesterol that have had longitudinal designs. A longitudinal study has the advantage of observing the temporal relationship between sleep duration and high cholesterol to strengthen the counterfactual argument that if short sleep duration had not occurred, then high cholesterol would not have occurred. Knowledge of the relationship between sleep duration and the incidence of hypocholesterolemia could lead to the development of interventions to decrease the morbidity and mortality associated with high cholesterol. In this study, we explored whether short sleep durations in adolescence would be associated with increased odds of having been diagnosed with high cholesterol 7 to 8 years later in young adulthood among subjects who participated in the National Longitudinal Study of Adolescent Health (Add Health). We hypothesized that physical activity, emotional distress, and body weight would act as mediators of the relationship. We theorized that the relationship would be stronger in women than in men given results from previous cross-sectional population based and experimental studies.

Separating the Contribution of Glucocorticoids and Wakefulness to the Molecular and Electrophysiological Correlates of Sleep Homeostasis

Abstract: Study Objectives: The sleep-deprivation–induced changes in delta power, an electroencephalographical correlate of sleep need, and brain transcriptome profiles have importantly contributed to current hypotheses on sleep function. Because sleep deprivation also induces stress, we here determined the contribution of the corticosterone component of the stress response to the electrophysiological and molecular markers of sleep need in mice.

Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study.

Abstract: AN INCREASED FREQUENCY OF IMPULSE CONTROL DISORDERS (ICDS) HAS BEEN RECOGNIZED WITH THE USE OF DOPAMINERGIC AGENTS IN A SUBSET OF patients with Parkinson disease (PD). The central dopaminergic reward system has been implicated, possibly due to overstimulation of mesolimbic dopamine receptors.1 Recognized ICDs in this setting include pathologic gambling,2–7 hypersexuality,7–9 compulsive shopping,7,9 compulsive eating,10 punding,11–14 and compulsive medication use.15 Punding is characterized by complex, stereotyped, and often purposeless repetitive actions such as continued handling or sorting of common objects, manipulation of technical equipment, excessive grooming or cleaning, and hoarding.13,14 Several of these entities are formally designated as “impulse control disorders” in the Diagnostic and Statistical Manual of Mental Disorders (4th Edition),16 but this group of behaviors can be recognized as a whole by a common inability to resist impulses, drive, or temptation to engage in ultimately self-destructive acts. Controversy remains regarding their overall classification because of overlap with obsessive-compulsive and addiction processes. In patients with PD, ICDs are relatively common, with estimated lifetime prevalence rates of 3% to 8% for pathologic gambling, 2.5% to 7.2% for hypersexuality, and 0.4% to 1.5% for compulsive shopping.1,7 For comparison, the lifetime prevalence of pathologic gambling in the general population is between 0.3% and 2%.1,3,17–19 Similar data for other ICDs are less well established. One questionnaire-based study demonstrated an overall lifetime prevalence of pathologic gambling, hypersexuality, or compulsive shopping in patients with PD of 6.1% but a statistically significant heightened rate of 13.7% with the use of dopaminergic agonists in this population.9 The individual lifetime prevalence rates in the subset of patients using dopaminergic agonists in this study were 7.2% for pathologic gambling, 7.2% for hypersexuality, and 1.4% for compulsive shopping.9 A recent retrospective analysis of 267 local patients with PD found new-onset compulsive gambling or hypersexuality in 18.4% of subjects taking therapeutic doses of dopamine agonists (defined as ≥ 2 mg of pramipexole or 6 mg of ropinirole daily).20 Numerous reports in the literature confirm a similar striking relationship between ICDs and the use of dopaminergic agents in PD.1–10,12,15 A consistent dose effect has not been demonstrated.1 The relationship between ICDs and the use of dopaminergic medications in disease processes other than PD has not been as well studied. Several case reports suggest that pathologic gambling may have an increased frequency with the use of dopaminergic agonists in restless legs syndrome (RLS).19,21,22 A recent retrospective survey of 77 patients with idiopathic RLS actively taking dopaminergic medication found increased gambling in 6% and excessive sexual behaviors in 4% of the subjects.23 RLS is a common and important neurologic disorder. Epidemiologic studies suggest that 10% to 15% of adults in European and North American countries meet criteria for diagnosis, including 2.5% in which the condition seriously affects quality of life.24–27 Although the precise pathophysiology remains unknown, dysfunction of central dopaminergic systems has been implicated, and dopaminergic agents are widely used for treatment of symptoms.28 Given the potentially devastating psychosocial consequences of ICDs, a better understanding of the frequency of these behaviors is essential to improve medical management of RLS. We performed a prospective, case-control study to determine the frequency of ICDs in patients with RLS using dopaminergic agents. Our primary hypothesis was that the frequency would be higher than in a comparative group of patients with obstructive sleep apnea (OSA).