Showing papers in "Sleep in 2009"

Insomnia with objective short sleep duration is associated with a high risk for hypertension.

Abstract: INSOMNIA IS, BY FAR, THE MOST COMMONLY ENCOUNTERED SLEEP DISORDER IN MEDICAL PRACTICE. HOWEVER, RELATIVELY LITTLE IS KNOWN about the mechanisms, causes, clinical course, and consequences of this highly prevalent chronic condition.1,2 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.1,2 However, in contrast to the other most common sleep disorder, sleep disordered breathing (SDB), chronic insomnia has not been linked with significant medical morbidity, e.g., cardiovascular disorders. Few studies that have examined the association of chronic insomnia with hypertension have reported modest and inconsistent effects of little or no clinical significance.3–6 In fact, Kripke et al. found a reduced mortality rate for those individuals complaining of sleep difficulties after 6 years of follow-up.7 Most, but not all, studies have reported that insomnia is associated with an overall hypersecretion of ACTH and cortisol, suggesting an activation of the hypothalamic-pituitary-adrenal (HPA) axis in these patients.8–11 Given the well-established association of hypercortisolemia with significant medical morbidity, e.g., hypertension, metabolic syndrome, osteoporosis,12 the paucity of data linking insomnia with these medical disorders is a paradox. In our studies, we observed and reported that the activation of the HPA axis in insomnia was strongly and positively correlated with objective indices of sleep disturbance.8,9 Specifically, hypercortisolemia was found primarily in insomniacs who demonstrated short sleep duration in the sleep laboratory but not in those whose objective sleep duration was similar to that of normal sleepers. Similarly, earlier studies have shown higher autonomic activation, including heart rate, 24-h metabolic rate, and impaired heart rate variability, in insomniacs selected based on objective polysomnographic criteria.13–16 Based on these observations, we speculate that objective short sleep duration may be an index of the biological severity of the disorder and that insomniacs with short sleep duration are at high risk for adverse medical outcomes. To test this hypothesis, we examined the joint effect of the complaints of chronic insomnia and poor sleep (a milder form of insomnia), and objective sleep duration on the prevalent hypertension in a large cross-sectional population-based sample from central Pennsylvania. We hypothesized that chronic insomnia is associated with a significant risk of hypertension, and that the comorbidity of insomnia and hypertension is enhanced by objective short sleep duration.

The New AASM Criteria for Scoring Hypopneas: Impact on the Apnea Hypopnea Index

Abstract: POLYSOMNOGRAPHY (PSG) IS PERFORMED FOR A WIDE VARIETY OF INDICATIONS, MOST COMMONLY FOR INVESTIGATION OF OBSTRUCTIVE SLEEP APNEA (OSA). OSA is characterized by repeated episodes of upper airway obstruction resulting in cessation (apnea) or reduction (hypopnea) in airflow during sleep. The apnea hypopnea index (AHI), a count of the number of apneas and hypopneas per hour of sleep, is the key measure used for case identification, for quantifying disease severity, and for defining disease prevalence in normal and clinical populations. Despite the importance of this measure, inter-laboratory variations in apnea and, in particular, hypopnea definition have been reported.1,2 Differences in hypopnea definition relate to the degree of airflow reduction and/or oxygen desaturation required and the requirement for associated EEG arousal. The effect of varying definitions of hypopnea on AHI has been examined in a number of studies3–6 and the importance of standardizing the hypopnea definition, and thereby reducing inter-laboratory variability in AHI, has been recognized.3,5,7,8 In 1999, the American Academy of Sleep Medicine (AASM) produced a consensus report,9 targeted at clinical research rather than clinical practice,10 recommending standardized scoring criteria for a range of respiratory events. These guidelines (also known as “Chicago Criteria”) described 2 types of hypopneas: (i) Those with a > 50% decrease in a valid measure of airflow without a requirement for associated oxygen desaturation or arousal, and (ii) Those with a lesser airflow reduction in association with oxygen desaturation of > 3% or an arousal. The lack of clinical practice guidelines was addressed in 2001 when the AASM, via the Clinical Practices Review Committee, published a position paper11 which described a hypopnea as an abnormal respiratory event lasting ≥ 10 sec with ≥ 30% reduction in thoracoabdominal movement or airflow, and with ≥ 4% oxygen desaturation. This is currently the approved hypopnea definition for the Centers for Medicare and Medicaid Services in the United States to determine eligibility for treatment funding.12 Nevertheless, in 2005 the AASM, via the Practice Parameters Committee, reported that, “Several clinical definitions of hypopnea are in clinical use and there is no clear consensus.”13 In a further attempt to improve standardization, the AASM recently published the Manual for the Scoring of Sleep and Associated Events.14 In this manual there is a “recommended” and an “alternative” hypopnea definition; and either can be used at the discretion of the clinician or investigator. The recommended definition is the same as the definition published in the AASM 2001 position paper: hypopnea scoring requires ≥ 30% reduction in nasal pressure signal excursions from baseline and associated ≥ 4% desaturation from pre-event baseline. The alternative definition requires ≥ 50% reduction in nasal pressure signal excursions and associated ≥ 3% desaturation or arousal. Introduction of new standards is likely to lead to a period when individual laboratories assess and change their practices and when different laboratories use different methodologies. This study aims to assist in interpretation of clinical or research results in this setting. Specifically, this study examines the impact of the 2 recently published hypopnea definitions on the AHI, compared to the previously published “Chicago” hypopnea definition, and subsequently examines the impact on the measured prevalence of OSA in a cohort of patients presenting for diagnosis or exclusion of obstructive sleep apnea. Compared to similar previous studies3–6 it is unique in its focus on published standard hypopnea definitions.

The Economic Burden of Insomnia: Direct and Indirect Costs for Individuals with Insomnia Syndrome, Insomnia Symptoms, and Good Sleepers

Abstract: INSOMNIA IS A PREVALENT PUBLIC HEALTH PROBLEM, WITH BETWEEN 6% AND 10% OF THE POPULATION MEETING DIAGNOSTIC CRITERIA FOR INSOMNIA syndrome1–3 and about a third of the population experiencing insomnia symptoms at any given moment.2 Despite its high prevalence, there is little information on the economic burden of insomnia. Information on the costs of illnesses, an indicator of their burden to society, is increasingly driving policy decisions about the funding and development of health care and research programs and priorities. Insurance companies are also concerned with the costs of illnesses and the impact that interventions may have in reducing symptoms and health care system utilization. Economic evaluations of the cost of illnesses or the cost effectiveness of treatments consider 2 broad categories of costs. These include direct costs associated with the consumption of resources (e.g., consultations, products, and testing), and indirect costs associated with the loss of resources (e.g., absenteeism, reduced productivity).4 While studies show a relationship between insomnia severity and the use of health-care service and product utilization,5–9 quantification of the associated costs is scarce. Similarly, some studies have reported a relationship between insomnia, increased absenteeism, and decreased productivity,10–13 yet the economic burden of this has been less frequently measured. The National Commission on Sleep Disorders Research estimated the direct costs of insomnia in the United States at $13.9 billion for the year 1995,14 whereas Leger et al.15 estimated the total cost of insomnia in France at about 10 million francs (or $2 billion US). The indirect costs associated with insomnia have received less attention in the literature, primarily because these costs are more difficult to estimate and quantify, there is no single database from which to draw, and measurement of these variables is more subject to interpretation and memory bias. Stoller16 attempted to quantify work-related deficits by combining data obtained in a study of workplace performance in Navy servicemen17 with her own insomnia prevalence estimate of 33% and a performance decrement estimate of 4%. The monetary value of absenteeism and lost productivity was estimated at $41.1 billion annually (1995 US$). A per person estimate was attempted by Chilcott and Shapiro,5 who suggest a decrease in work productivity due to insomnia of 10%. This amounts to $3,000 per insomnia sufferer per year. Stoller16 also looked at a number of other indirect costs, including insomnia-related accidents, alcoholism, and depression, estimating their costs at between $77.05 and $92.13 billion. Although these estimates have been criticized because they are based on liberal prevalence rates and relied on some questionable assumptions,9 they are still frequently used to describe the indirect economic consequences of insomnia. A French study18 concluded that insomnia is associated with increased absenteeism and reduced productivity, with associated costs about twice as high for insomnia patients as for good sleepers. The methods of costing did not allow, however, for an analysis of the proportional contribution of insomnia. There was also a methodological problem associated with double-counting costs that may have inflated cost estimates. Using existing data banks, Hillman et al.19 estimated the financial costs of all sleep disorders combined (e.g., insomnia, sleep apnea, periodic limb movements) for Australia at about $1,524 million, or 0.8% of the Australian gross domestic product. While an innovative approach was used to estimate fractions of other health impacts attributable to sleep disorders, this study did not permit the identification of costs associated with individual sleep disorders. A recent study by Ozminkowski et al.20 used medical claims data for health-care services, and absenteeism and short-term disability records to assess costs of insomnia occurring in adults in the US. After matching adult (aged 18–64) subsamples on variables determined by propensity score analysis, indirect costs combined were $1,253 higher in individuals with insomnia as compared to those without insomnia. The matching procedure and use of objective data lend strength to this study. However, costs related to reduced productivity, transportation, use of alcohol, and use of over-the-counter products were excluded from the analysis, suggesting that the results may underestimate the real cost of insomnia. Despite recent progress in documenting the economic burden of insomnia, some methodological weaknesses limit the current state of knowledge on this topic. The use of large administrative databases precludes analysis of potential confounding variables such as the reasons for consultations, use of OTC products, actual consumption of prescribed medications and, for some medications, the target ailment for which it was prescribed. When workplace records are used to obtain absenteeism data, reasons for absences are rarely provided and productivity data are not available. Similarly, the use of official accident records precludes identification of the contributing role of insomnia to these events. Studies typically use 2 groups—individuals with and without insomnia; the inclusion of an intermediate category would allow analysis of a linear relationship between costs and insomnia severity. The purpose of this study was to estimate, from the societal perspective, direct and indirect costs of insomnia. Costs were compared across three groups of participants classified as being good sleepers, having insomnia symptoms or having insomnia syndrome. The proportional contribution of insomnia to overall consultation costs and three indirect dependent cost variables, absenteeism, productivity and accidents, was also calculated.

Sleep disordered breathing in children in a general population sample: prevalence and risk factors.

Abstract: THE PREVALENCE OF SLEEP DISORDERED BREATHING (SDB) IN CHILDREN, BASED ON OBJECTIVE FINDINGS, HAS BEEN ESTIMATED IN SEVERAL STUDIES.1–10 These prevalence estimates have varied widely from 0.7% to 13.0%. This wide range of prevalence is at least partially due to the fact that SDB in children was defined based on an assortment of methods of assessing for the presence of SDB. These methods included: only hemoglobin oxygen saturation (SpO2)2,8; SpO2 + airflow3,4; and SpO2 + airflow + effort.5,7,9 Only 3 of these studies used a full polysomnogram (PSG),1,6,10 however, the number of subjects evaluated in these PSG studies was very small (N = 12–50). The majority of these studies had relatively narrow age ranges,2–4,6–10 while others had relatively wide age ranges.1,5 Some of these studies were primarily focused on ages < 6 years 2–4,8 while others included subjects as old as 18 years.1,5 Another limitation of the available studies is that they have not systematically assessed a wide range of risk factors that may contribute to SDB in children. This may reflect the paucity studies large enough to evaluate potential variables. Thus, the objectives of this study were (1) to establish the prevalence of SDB based on cutoff points of respiratory events that we have previously observed to be associated with a clinically significant risk (i.e., elevated systolic blood pressure), and (2) to identify independent risk factors for SDB. This study is based on the largest population-based sample of elementary school-aged children available to date.

Sleep duration and biomarkers of inflammation.

Abstract: MOUNTING EVIDENCE FROM BOTH OBSERVATIONAL AND EXPERIMENTAL RESEARCH SUGGESTS SLEEP DURATION PLAYS AN IMPORTANT ROLE IN HEALTH. Studies suggest both short and extended durations of sleep are associated with increased risk for all-cause mortality, coronary heart disease, diabetes, and obesity.1–5 The mechanisms by which altered sleep duration affects health are unclear, but experimental studies suggest altered sleep may impact levels of cytokines known to be important in regulating inflammation. Experimental sleep deprivation has been shown to acutely elevate pro-inflammatory cytokine levels including C-reactive protein (CRP) and interleukin-6 (IL-6).6–8 However, it is not clear whether this pro-inflammatory effect observed with short-term sleep deprivation experiments persists chronically. While one week of modest sleep restriction has been associated with elevations in IL-6 and tumor necrosis factor alpha (TNFα),9 a large population based study found no relationship between habitual sleep duration in the long term and CRP levels.10 Because chronic elevations in cytokines such as CRP and IL-6 are associated with an increased risk of adverse health outcomes such as diabetes and heart disease,11–13 any effect of sleep duration on regulation of these cytokines could have important long-term health effects. In this study, we sought to use a well-characterized cohort with standardized polysomnography (PSG) that allowed careful adjustment for sleep apnea severity, to examine whether an association exists between sleep duration and inflammatory mediators that might explain the associations between sleep duration and disease.

Incidence and risk factors of insomnia in a population-based sample.

Abstract: INSOMNIA IS AMONG THE MOST PREVALENT HEALTH COMPLAINTS. APPROXIMATELY 9% OF THE GENERAL POPULATION REGULARLY SUFFER FROM INSOMNIA, and about 30% do so occasionally.1–3 Incidence rates reported in longitudinal studies vary extensively (from 3% to 20%), depending on the population studied, the time interval (e.g., 1 year versus 10 years), and the definition of insomnia used (i.e., insomnia syndrome versus symptoms). For instance, it is estimated that over a period of one year, approximately 6% of the general population develop an insomnia syndrome,4 and approximately 20% develop insomnia symptoms, with the latter figures being based on samples of older adults5 and individuals with chronic health problems.6 Furthermore, new onset of insomnia is generally more frequent among women and individuals with medical conditions, psychiatric disorders, and a perceived stressful life.4,7–9 Based on a tripartite conceptual framework widely used to explain the development of insomnia,10–12 3 types of factors are involved at different times during the course of insomnia. First, everyone is, to some degree, predisposed to develop insomnia. Second, a precipitating event is usually associated with the onset of insomnia. Third, insomnia is perpetuated over time by psychological and behavioral factors, even after precipitating factors have been controlled or eliminated. The most commonly hypothesized predisposing factors include demographic factors (e.g., aging, female gender, living alone),1,3,13 familial/hereditary conditions (a personal or family history of insomnia),14–16 psychological factors (e.g., anxiety, depression, personality traits),4,17–19 and physiological and lifestyle factors (e.g., arousability and smoking).20,21 Precipitating factors include stressful life events (e.g., divorce),9,22 as well as psychological and health-related factors (e.g., pain, mental health problems).10,23 Finally, maintaining factors include maladaptive sleep habits (e.g., excessive amounts of time spent in bed, napping, chronic medication use) and dysfunctional cognitions about sleep loss and its impact on life (e.g., worry over sleep loss).10 Most studies investigating insomnia risk factors have been either retrospective or cross-sectional, precluding unequivocal inference about the relationship between these factors and the development of insomnia. The extent to which depression and anxiety trigger insomnia or represent consequences of insomnia remains ambiguous. The few longitudinal studies of insomnia have provided informative data about incidence and risk factors, although most of those studies have focused predominantly on selected samples such as young adults,7,28 elderly adults,8,24,25 or patients attending medical practices.6,26,27 Only one longitudinal study evaluating the relation between sleep problem symptoms (i.e., insomnia and hypersomnia) and psychiatric disorders sampled the population at large.4 Few studies have used standard diagnostic criteria to define insomnia. Moreover, previous studies have used various time frames and most have not adequately operationalized their measure of incidence. For instance, most studies have not differentiated between incident cases of first episode of insomnia (no prior history of insomnia) and cases of recurrence (with past history of insomnia). Furthermore, the majority of studies included only individuals experiencing insomnia at the time of the second assessment in their incidence estimates5,6,8,29 rather than all cases emerging during the interval between baseline and follow-up assessment.7 Since insomnia may prove transient or episodic, incidence rates may have been underestimated in previous studies. The National Institutes of Health30 called for additional longitudinal studies using well-operationalized and stringent diagnostic criteria to estimate insomnia incidence and identify risk factors within the general population. The objectives of this study were to estimate the incidence of insomnia symptoms and syndrome and to identify associated risk factors in a cohort of good sleepers sampled from the general population and followed over a one-year period.

Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke.

Abstract: Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease. Sympathetic overactivity is associated with RLS/PLMS, as manifested by increased pulse rate and blood pressure coincident with PLMS. Causality is far from definitive. Mechanisms are explored as to how RLS/PLMS may lead to high blood pressure, heart disease, and stroke: (a) the sympathetic hyperactivity associated with RLS/PLMS may lead to daytime hypertension that in turn leads to heart disease and stroke; (b) in the absence of daytime hypertension, this sympathetic hyperactivity may predispose to heart disease and stroke either directly or indirectly via atherosclerotic plaque formation and rupture; and (c) comorbidities associated with RLS/PLMS, such as renal failure, diabetes, iron deficiency, and insomnia, may predispose to heart disease and stroke. One theoretical cause for sympathetic hyperactivity is insufficient All diencephalospinal dopaminergic neuron inhibition of sympathetic preganglionic neurons residing in the intermediolateral cell columns of the spinal cord. We cannot exclude the possibility that peripheral vascular, cardiovascular, and cerebrovascular disease may also contribute to RLS/PLMS, and mechanisms for these possibilities are also discussed.

Sleep Behaviors and Sleep Quality in Children with Autism Spectrum Disorders

Abstract: measurements and results : The CSHQ, sleep diaries, and 10 nights of actigraphy using the Sadeh algorithm of children with ASD and TD control subjects were compared. CSHQ showed 66.1% of parents of children with ASD (62.5% autism, 76.2% PDD-NOS, 58.3% Asperger disorder) and 45% of parents of the control subjects reported that their children had sleep problems. Actigraphic data showed that 66.7% of children with ASD (75% autism, 52.4% PDD-NOS, 75% Asperger disorder) and 45.9% of the control subjects had disturbed sleep. Conclusions : The prevalence estimate of 45% for mild sleep disturbances in the TD cohort highlights pediatric sleep debt as a public health problem of concern. The prevalence estimate of 66% for moderate sleep disturbances in the ASD cohort underscores the significant sleep problems that the families of these children face. The predominant sleep disorders in the ASD cohort were behavioral insomnia sleep-onset type and insomnia due to PDD.

Lucid dreaming: a state of consciousness with features of both waking and non-lucid dreaming.

Abstract: study objectives : The goal of the study was to seek physiological correlates of lucid dreaming. Lucid dreaming is a dissociated state with aspects of waking and dreaming combined in a way so as to suggest a specific alteration in brain physiology for which we now present pre liminary but intriguing evidence. We show that the unusual combination of hallucinatory dream activity and wake-like reflective awareness and agentive control experienced in lucid dreams is paralleled by significant changes in electrophysiology. design : 19-channel EEG was recorded on up to 5 nights for each participant. Lucid episodes occurred as a result of pre-sleep autosuggestion. setting : Sleep laboratory of the Neurological Clinic, Frankfurt University. Participants : Six student volunteers who had been trained to become lucid and to signal lucidity through a pattern of horizontal eye movements. Measurements and results : Results show lucid dreaming to have REMlike power in frequency bands δ and θ, and higher-than-REM activity in the γ band, the between-states-difference peaking around 40 Hz. Power in the 40 Hz band is strongest in the frontal and frontolateral region. Overall coherence levels are similar in waking and lucid dreaming and significantly higher than in REM sleep, throughout the entire frequency spectrum analyzed. Regarding specific frequency bands, waking is characterized by high coherence in α, and lucid dreaming by increased δ and θ band coherence. In lucid dreaming, coherence is largest in frontolateral and frontal areas. conclusions : Our data show that lucid dreaming constitutes a hybrid state of consciousness with definable and measurable differences from waking and from REM sleep, particularly in frontal areas.

"Stepped care": a health technology solution for delivering cognitive behavioral therapy as a first line insomnia treatment.

Abstract: There is a large body of evidence that Cognitive Behavioral Therapy for insomnia (CBT) is an effective treatment for persistent insomnia However, despite two decades of research it is still not readily available, and there are no immediate signs that this situation is about to change This paper proposes that a service delivery model, based on "stepped care" principles, would enable this relatively scarce healthcare expertise to be applied in a cost-effective way to achieve optimal development of CBT services and best clinical care The research evidence on methods of delivering CBT, and the associated clinical leadership roles, is reviewed On this basis, self-administered CBT is posited as the "entry level" treatment for stepped care, with manualized, small group, CBT delivered by nurses, at the next level Overall, a hierarchy comprising five levels of CBT stepped care is suggested Allocation to a particular level should reflect assessed need, which in turn represents increased resource requirement in terms of time, cost and expertise Stepped care models must also be capable of "referring" people upstream where there is an incomplete therapeutic response to a lower level intervention Ultimately, the challenge is for CBT to be delivered competently and effectively in diversified formats on a whole population basis That is, it needs to become "scalable" This will require a robust approach to clinical governance

Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study

Abstract: PREVIOUS COHORT STUDIES HAVE DEMONSTRATED THAT SHORT OR LONG SLEEP DURATION IS ASSOCIATED WITH THE INCIDENCE OF OR MORTALITY FROM cardiovascular disease,1–4 as well as total mortality.1,3–6 The National Health and Nutrition Examination Survey I showed a 1.5-fold increase in the risk of stroke for persons with more than 8 hours of sleep, compared with those with 6 to 8 hours of sleep.1 The Nurse's Health Study also reported that, compared with 8 hours of sleep, short or long sleep duration of 5 or more hours or 9 or more hours was associated with an increased incidence of coronary heart disease for women aged 40 to 65 years,2 and, compared with 7 hours of sleep, long sleep duration of 9 or more hours was associated with mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes, whereas short sleep duration of 5 hours or less was associated with mortality from all causes and noncardiovascular disease for women aged 40 to 65 years.3 The Whitehall II cohort study found a U-shaped association between sleep duration and mortality from cardiovascular disease and noncardiovascular disease and between sleep duration and all causes for men and women aged 35 to 55 years.4 An earlier report of our Japanese cohort study5 also showed a U-shaped relationship between sleep duration and total mortality, but cause-specific analyses were not carried out. Thus, the association between short or long sleep duration and mortality from cardiovascular disease and other causes for Japanese men and women has remained unclear. To examine the sex-specific associations of sleep duration and mortality from stroke, coronary heart disease, and other causes, as well as total mortality, we analyzed the extended follow-up data from a large-scale prospective study of approximately 98,000 Japanese men and women.

Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset

Abstract: NARCOLEPSY-CATAPLEXY IS A LIFELONG, DISABLING NEUROLOGICAL DISORDER, AFFECTING 1 IN 2000. CHARACTERISTIC SYMPTOMS INCLUDE EXCESSIVE daytime sleepiness and episodes of sudden loss of muscle tone, triggered by strong emotions (cataplexy). Onset is typically during adolescence, and predisposition involves both genetic and non-genetic factors, as suggested by the low monozygotic concordance but increased familial predisposition.1 The disorder is unique because of its extremely tight association with HLA-DQB1*0602 and hypocretin cell loss, suggesting autoimmune destruction; only 5 patients in the world have been described with low CSF hypocretin-1, a marker of hypocretin cell destruction, and DQB1*0602 negativity.2 Recently, using a Genome Wide Association, we found association with polymorphisms in the T-cell receptor α (TCR) loci.3 TCR is the major receptor of HLA-peptide presentation, and plays a critical role in mediating immune responses in normal (e.g., infectious) or abnormal (e.g., autoimmune) responses. Whereas much progress has been made toward understanding genetic predisposition in narcolepsy, little is known regarding environmental triggers. Retrospective questionnaire studies have found increased stress and decreased sleep amounts prior to narcolepsy onset.4 Case reports, describing a few unusual cases, have found sudden onset of narcolepsy 3 days after head trauma5 or various other unusual triggers (bee sting, etc). In all these cases, however, findings may be coincidental and are likely confounded by bias recall. More recently, a well-designed population based study of narcolepsy has been initiated and found increased smoking exposure in patients with narcolepsy as a risk factor6; the authors suggested the effect to be secondary to increased upper respiratory tract infections in secondary smoking. This, together with the report more than 20 years ago of increased ASO and ADB titers in a small number of narcoleptic patients regardless of disease duration,7,8 a finding that was later refuted,9 led us to reexamine the topic of infectious trigger in narcolepsy. It has been our clinical experience that narcolepsy is increasingly recognized close to onset, whereas 10-20 years ago, the disorder was diagnosed more than 10 years after onset (median time).10 We reasoned that a possible infectious trigger would not be detectable long after onset of narcolepsy, thus explaining variable results obtained in these first studies. Indeed, we also ourselves attempted to duplicate these anti-streptococcal findings in long standing narcolepsy cases, but could not find any differences with controls (Scott Fromhertz, unpublished results). We hypothesized that if streptococcal infections were indeed a trigger for narcolepsy onset, it would be best detected in newly identified patients, many of which had recent onset.

Sleep classification according to AASM and Rechtschaffen & Kales: effects on sleep scoring parameters.

Abstract: FOR APPROXIMATELY 40 YEARS THE ONLY WIDELY ACCEPTED STANDARD FOR DESCRIBING THE HUMAN SLEEP PROCESS WAS THE MANUAL OF SLEEP CLASSIFICATION by Rechtschaffen and Kales.1 On the basis of these scoring rules, sleep recordings are divided into 7 discrete stages (wake, stage 1, stage 2, stage 3, stage 4, stage REM, and movement time). Even though in many cases this standard is useful, the rules of Rechtschaffen and Kales have also been criticized for leaving plenty of room for subjective interpretation, which leads to a great variability in the visual evaluation of sleep stages.2,3 Last but not least, the standard rules were developed for young healthy adults4,5 and do not necessarily directly apply to elderly subjects and patients. The American Academy of Sleep Medicine (AASM)6 modified the standard guidelines for sleep classification by Rechtschaffen and Kales and developed a new guideline for terminology, recording method, and scoring rules for sleep-related phenomena. The manual is the result of a review of literature, analysis and consensus which addresses 7 topics: digital analysis and reporting parameters, visual scoring, arousal, cardiac and respiratory events, movements and pediatric scoring. One of the major changes is a change in terminology: in the AASM classification, sleep stages S1 to S4 are referred to as N1, N2, and N3, with N3 reflecting slow wave sleep (SWS, RK stage REM is referred to as stage R. According to the AASM manual, a minimum of 3 EEG derivations, sampling activity from the frontal, central, and occipital regions, has to be recorded. The recommended derivations are F4-M1, C4-M1, and O2-M1 (right-sided active electrodes and a reference over the left mastoid, rather than the ear).7 The new manual also deals with the definition of the sleep-wake transition, sleep spindles, K-complexes, slow wave sleep, and REM sleep, as well as arousals and major body movements. In summary, the major changes of the new manual comprise EEG derivations, the merging of stages 3 and 4 into N3, the abolition of stage “movement time,” the simplification of many context rules as well as the recommendation of sampling rates and filter settings for polysomnographic (PSG) reporting and for user interfaces of computer-assisted sleep analysis.6 To date there are no studies evaluating the effects of the new standard on sleep scoring data. The aim of the present investigation was to describe in detail differences between visual sleep scoring according to the Rechtschaffen and Kales classification and scoring based on the new AASM guidelines in normal subjects of different age groups and sleep-disturbed patients.

Molecular signatures of obstructive sleep apnea in adults: a review and perspective

Abstract: The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.

Sleep and depression in postpartum women: a population-based study.

Abstract: Study Objectives: (1) To describe the prevalence of and risk factors for postpartum maternal sleep problems and depressive symptoms simultaneously, (2) identify factors independently associated with either condition, and (3) explore associations between specific postpartum sleep components and depression.

A Nightly Bedtime Routine: Impact on Sleep in Young Children and Maternal Mood

Abstract: SLEEP PROBLEMS ARE ONE OF THE MOST COMMON CONCERNS OF PARENTS OF YOUNG CHILDREN, OCCURRING IN APPROXIMATELY 20% TO 30% OF INFANTS AND toddlers,1,2 and one of the most common behavioral issues brought to the attention of pediatricians.3,4 There are a number of studies on the efficacy of behavioral interventions for the sleep problems, and the American Academy of Sleep Medicine has even released a standards of practice document for behavioral treatment of bedtime problems and night wakings in young children.1,5 Overall, it was found that of 52 treatment studies reviewed, 94% reported that behavioral interventions were efficacious and 80% of children treated demonstrated clinically significant improvement. Noteworthy was that the majority of the intervention studies reviewed included a bedtime routine as part of a multi-component treatment program. However, no studies have ever evaluated the efficacy of a bedtime routine independent of other treatments. A bedtime routine is a common and simple behavioral intervention for sleep issues in young children, with over 90% of pediatricians recommending institution of a bedtime routine to their patients with sleep difficulties.3 Research shows that daily routines in general lead to predictable and less stressful environments for young children and are related to parenting competence, improved daytime behaviors, and lower maternal mental distress.6–8 A bedtime routine is one such daily family routine and consists of parents engaging their child in the same activities in the same order on a nightly basis prior to turning out the lights (“lights out”). It is expected that a bedtime routine will similarly improve behavior and will result in children falling asleep quicker with less disruptive behaviors at bedtime. Furthermore, in considering the efficacy of sleep-related interventions on children, it is important to note that sleep issues in young children also have a significant negative impact on parents. For example, studies have found elevated levels of depressed mood in mothers of infants and toddlers having sleep disturbances.9,10 Conversely, studies indicate that successful treatment of children's sleep problems with behavioral interventions results in improvements in parental well-being.11,12 Therefore, improvement in parental mood following institution of a bedtime routine is also expected given that routines overall result in reduced parental distress, as discussed above. Thus, the overall objectives of the current studies were to examine the effects of a consistent bedtime routine on infant and toddler sleep, as well as its impact on maternal mood. We hypothesized that a bedtime routine would result in (1) decreased sleep onset latency, (2) reduction of disruptive bedtime behaviors, and (3) improved maternal mood.

Race and Financial Strain are Independent Correlates of Sleep in Midlife Women: The SWAN Sleep Study

Abstract: MOUNTING EVIDENCE SUGGESTS THAT SLEEP DIFFERS SIGNIFICANTLY ACROSS RACIAL AND ETHNIC GROUPS IN WAYS THAT MAY BE IMPORTANT TO health and functioning.1–5 Most consistent among these effects is a marked decrease in laboratory-assessed slow wave sleep and a concomitant increase in stages 1 and 2 of NREM sleep in African Americans compared to Caucasians.3–7 Other dimensions of sleep shown to differ between African Americans and Caucasians include sleep duration, continuity and subjective sleep quality, although these relationships are not as strong and consistent as those observed for sleep architecture.8 Far fewer studies have compared sleep across other racial and ethnic groups. Hale and Do9 evaluated data from 32,749 respondents to the 1990 health promotion supplement of the National Health Interview Survey (NHIS) and found that, compared to Caucasians, the prevalence of short sleepers (< 6 hours/night) was higher among all racial and ethnic minorities surveyed including African Americans, Hispanics and non-Hispanic “others.” As measured by one night of in-home polysomnography (PSG) collected in the population-based Sleep Heart Health Study (SHHS), Redline and colleagues reported that American Indians and African Americans had lighter sleep than Caucasians, Hispanics, or Asian Americans.10 Despite growing evidence that sleep differs by race and/or ethnic minority status, few studies have evaluated possible causes or correlates of these differences. It has been suggested that socioeconomic status (SES), which is closely tied to race and ethnic minority status in many countries, including the United States, may play an important role in the relationship between minority racial/ethnic status and disturbed sleep.5,6,11 Indeed, a number of studies have reported significant associations among subjective sleep complaints and various indices of SES including lower education, occupational status and income, although these studies did not evaluate the influence of race on the SES-sleep relationship.12–17 Three recent studies reported that both race/ethnicity and traditional measures of SES, income, and education, were significant correlates of behavioral or PSG-assessed indices of sleep.2,6,18 For instance, Mezick and colleagues evaluated the independent effects of race and SES on sleep in a cohort of midlife men and women who were self-identified as either non-Hispanic Caucasian or African American. Lower SES, as measured by a composite score of income and education, was associated with greater PSG-assessed wakefulness after sleep onset, after adjusting for other confounding variables, including race. Sleep quality, duration, and architecture were unrelated to SES in the Mezick et al., study. These studies provide some support for the hypothesis that certain dimensions of sleep may be related to traditional markers of SES, independent of race. The extent to which other dimensions of SES affect, or are affected by, sleep have received less empirical attention. We have hypothesized that financial strain, which is a key chronic stressor associated with lower SES, may be a sensitive marker of the SES-sleep relationship.11 We reported that financial strain, operationalized as difficulties with paying for basics like food and housing, was a significant correlate of increased subjective sleep quality complaints in a sample of 462 midlife women, one-third of whom were African American.11 In multivariate models, financial strain attenuated the relationship between income and sleep quality, which is consistent with the hypothesis that stress pathways are important to the SES-sleep relationship. Stress pathways by which financial strain might interfere with sleep include increased worries and negative affect, as well as endocrine and autonomic dysregulation.19–24 More recently, we demonstrated that chronic and ongoing financial strain was associated with significant decreases in PSG-assessed sleep efficiency in a large sample of community-dwelling elders, after adjusting for a host of variables known to impact sleep in late life.25 Although these studies suggest that financial strain may be an important correlate of sleep, the extent to which financial strain plays a role in the SES-sleep or race-sleep relationship has not been evaluated. The present study evaluated relationships among race and markers of SES in relation to sleep in a multiracial sample of midlife women enrolled in the SWAN Sleep Study, which was designed to characterize sleep during the menopausal transition. Sleep during the menopausal transition provides an opportune model for evaluating the influence of race and SES on sleep because subjective sleep complaints and some sleep disorders are much more frequent in perimenopausal and menopausal women.26–30 Moreover, sleep disturbances that arise during the menopausal transition may be a marker for the development of later chronic health conditions and declines in general health and functioning occurring in the postmenopausal years. SWAN Sleep Study participants included African American, Caucasian, and Chinese women. Measures of sleep were subjective sleep quality, as measured by the validated Pittsburgh Sleep Quality Index (PSQI),31 and indices of sleep duration, continuity, and architecture including NREM electroencephalographic (EEG) power, as measured by multinight in-home PSG. We hypothesized that African American race would be associated with worse sleep, compared to Caucasian and Chinese participants. We further hypothesized that markers of SES, as measured by educational attainment and financial strain, would affect the race-sleep relationship. Specifically, we hypothesized that lower educational attainment and financial strain would attenuate observed relationships among race and sleep after adjusting for other factors that might confound relationships among race, SES, and sleep in midlife women.

Long Working Hours and Sleep Disturbances: The Whitehall II Prospective Cohort Study

Abstract: STUDY OBJECTIVE: To examine whether exposure to long working hours predicts various forms of sleep disturbance; short sleep, difficulty falling asleep, frequent waking, early waking and waking without feeling refreshed. DESIGN: Prospective study with 2 measurements of working hours (phase 3, 1991-1994 and phase 5, 1997-1999) and 2 measurements of subjective sleep disturbances (phase 5 and phase 7, 2002-2004). SETTING: The Whitehall II study of British civil servants. PARTICIPANTS: Full time workers free of sleep disturbances at phase 5 and employed at phases 5 and 7 (n = 937-1594) or at phases 3, 5, and 7 (n = 886-1510). MEASUREMENTS AND RESULTS: Working more than 55 hours a week, compared with working 35-40 hours a week, was related to incident sleep disturbances; demographics-adjusted odds ratio (95% CI) 1.98 (1.05, 3.76) for shortened sleeping hours, 3.68 (1.58, 8.58) for difficulty falling asleep; and 1.98 (1.04, 3.77) for waking without feeling refreshed. Repeat exposure to long working hours was associated with odds ratio 3.24 (1.45, 7.27) for shortened sleep, 6.66 (2.64, 16.83) for difficulty falling asleep, and 2.23 (1.16, 4.31) for early morning awakenings. Some associations were attenuated after adjustment for other risk factors. To a great extent, similar results were obtained using working hours as a continuous variable. Imputation of missing values supported the findings on shortened sleep and difficulty in falling asleep. CONCLUSION: Working long hours appears to be a risk factor for the development of shortened sleeping hours and difficulty falling asleep.

Cognitive behavioral therapy for patients with primary insomnia or insomnia associated predominantly with mixed psychiatric disorders: a randomized clinical trial.

Abstract: CHRONIC INSOMNIA IS A SERIOUS FORM OF SLEEP DISTURBANCE ASSOCIATED WITH REDUCED QUALITY OF LIFE, INCREASED RISKS FOR SERIOUS PSYCHIATRIC illness, and enhanced healthcare utilization among millions worldwide.1–3 Insomnia may present either as a primary sleep disorder or as a disorder comorbid with another sleep, medical, or psychiatric disorder or a combination thereof. Both primary insomnia (PI) and comorbid insomnia (CMI) are relatively common maladies, but CMI is more prevalent than PI in both clinical venues4,5 and the general population at large.6 Moreover, CMI may be more persistent and have even more serious consequences than PI. Recent data,7 for example, show that insomnia sufferers with comorbid gastrointestinal problems, chronic pain, hypertension, or problems with breathing or urination report more chronic insomnia than do those without such conditions. Furthermore, when insomnia occurs comorbid with a psychiatric illness such as major depression, it complicates disease management and often remains as a residual symptom that enhances risk for both suicide and relapse.8,9 In view of these considerations, patients who present with insomnia and particularly those with CMI warrant early and effective treatment. Pharmacotherapy with benzodiazepine receptor agonists or sedating antidepressants currently remains the most common treatment offered to patients with insomnia.10 However, cognitive behavioral therapy (CBT), designed to address sleep-disruptive beliefs and habits, has become an increasingly well-regarded insomnia treatment.10 Results of meta-analyses (e.g., Smith, et al.11) and head-to-head comparisons12 suggest CBT produces short-term sleep improvements that compare favorably to those achieved with various forms of pharmacotherapy. Furthermore, sleep improvements following CBT appear to endure long after treatment is completed,13 and limited data suggest that patients prefer CBT over treatment with sleep medications.14 Given such observations, CBT has become a popular alternative for insomnia management. Most evidence supporting the efficacy of CBT comes from studies conducted with patients with PI, although there is some limited evidence supporting use of this treatment with CMI as well. Some uncontrolled case series or clinic-based studies have suggested the efficacy of CBT among patients with CMI and mixed psychiatric and medical conditions.15 Other case series or quasi-experimental studies have suggested CBT may be efficacious for treating insomnia in such specific patient groups as those with chronic pain,16 cancer,17 posttraumatic stress disorder,18 and clinical depression19 and those with mixed serious mental disorders.20 In addition, a number of small to moderately sized, single-site, randomized clinical trials have suggested that CBT is efficacious for patients with insomnia and comorbid chronic peripheral pain syndromes,21 treated breast cancer,22 fibromyalgia23, mixed medical disorders,24 mixed psychiatric and medical disorders,25 and alcoholism.26 Despite these findings, it is yet to be determined whether patients with PI or CMI show similar improvement from an equal and standard dose of CBT intervention. The current study tested the relative efficacy of CBT against a sleep hygiene control treatment (SH) in patients with PI and in a group of patients with CMI composed predominantly of individuals with mixed comorbid psychiatric disorders. The study hypotheses predicted that CBT would produce significantly greater short- and longer-term improvements in insomnia symptoms than would sleep hygiene in the sample as a whole. The data obtained were also examined to assess the relative efficacy of CBT in the PI and CMI groups considered separately.

Sleep-dependent improvement in visuomotor learning: a causal role for slow waves.

Abstract: STUDY OBJECTIVES: Sleep after learning often benefits memory consolidation, but the underlying mechanisms remain unclear. In previous studies, we found that learning a visuomotor task is followed by an increase in sleep slow wave activity (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz during non-rapid eye movement sleep) over the right parietal cortex. The SWA increase correlates with the postsleep improvement in visuomotor performance, suggesting that SWA may be causally responsible for the consolidation of visuomotor learning. Here, we tested this hypothesis by studying the effects of slow wave deprivation (SWD). DESIGN: After learning the task, subjects went to sleep, and acoustic stimuli were timed either to suppress slow waves (SWD) or to interfere as little as possible with spontaneous slow waves (control acoustic stimulation, CAS). SETTING: Sound-attenuated research room. PARTICIPANTS: Healthy subjects (mean age 24.6 +/- 1.0 years; n = 9 for EEG analysis, n = 12 for behavior analysis; 3 women). MEASUREMENTS AND RESULTS: Sleep time and efficiency were not affected, whereas SWA and the number of slow waves decreased in SWD relative to CAS. Relative to the night before, visuomotor performance significantly improved in the CAS condition (+5.93% +/- 0.88%) but not in the SWD condition (-0.77% +/- 1.16%), and the direct CAS vs SWD comparison showed a significant difference (P = 0.0007, n = 12, paired t test). Changes in visuomotor performance after SWD were correlated with SWA changes over right parietal cortex but not with the number of arousals identified using clinically established criteria, nor with any sign of "EEG lightening" identified using a novel automatic method based on event-related spectral perturbation analysis. CONCLUSION: These results support a causal role for sleep slow waves in sleep-dependent improvement of visuomotor performance.

Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder.

Abstract: TEMPOROMANDIBULAR JOINT DISORDER (TMD) HAS BEEN DESCRIBED AS A PROTOTYPIC IDIOPATHIC PAIN SYNDROME CHARACTERIZED BY POORLY understood, episodic, masticatory muscle and/or joint pain. TMD affects an estimated 12% of the population.1 As in other idiopathic pain disorders such as fibromyalgia and irritable bowel syndrome, patients often present with overlapping signs and symptoms including psychological distress, neuroendocrine abnormalities, and chronic insomnia.2,3 Recent theoretical perspectives have proposed that these “central sensitivity syndromes” share a common central nervous system substrate characterized by heightened processing of noxious input, which contributes to overlapping daytime sequelae among these disorders.4 Several cross-sectional studies have demonstrated that compared to controls, TMD patients exhibit enhanced responsivity to a variety of painful stimuli measured both at facial and extracranial anatomic sites.5–7 Pain sensitivity at “unaffected” (i.e., non-jaw) sites suggests the involvement of central pain processing mechanisms, beyond peripheral contributions. Recent longitudinal work has reported that enhanced laboratory pain sensitivity in pain free individuals is linked to genetic polymorphisms that predict the development of new onset TMD.8 This suggests that central processes associated with pain amplification may be critical to understanding the etiopathophysiology of TMD. Clinical factors that contribute to pain amplification in TMD, however, are poorly understood. Our group has focused on the possibility that sleep disturbance is one such factor that may directly contribute to central sensitization and pain amplification.9 We recently reported, for example, that sleep onset insomnia symptoms predict the development of chronic pain following serious burn injury.10 While it is often assumed that insomnia or sleep loss occurring in the context of chronic pain occurs secondarily to the sleep interrupting effects of pain, we and others have demonstrated that insomnias associated with chronic pain are often phenotypically similar to primary insomnia.11 Shared features include high levels of pre-sleep cognitive rumination and evidence of maladaptive coping strategies that may exist prior to the development of pain and/or independently contribute to insomnia symptoms. It is unknown, however, whether primary insomnia is associated with alterations in laboratory pain sensitivity when it occurs either as a sole condition or as part of a chronic pain disorder such as TMD. Only a handful of investigations have systematically sought to evaluate the sleep quality of TMD patients. These studies have consistently found that the majority ( > 50%) of TMD patients report poor sleep quality, and that subjective ratings of poor sleep are associated with increased clinical pain severity and psychological distress.12–14 Fundamental descriptive data using polysomnography and standard research diagnostic interviews to quantify the range of sleep disorders in TMD and determine their possible associations with laboratory measures of pain sensitivity are lacking. The extant literature has largely focused on possible relationships between sleep bruxism and TMD.15,16 Sleep bruxism, however, has not been found to be associated with either poor sleep quality or polysomnographic measures of sleep continuity or architecture disturbances.17–19 The objective of this study was to address two critical gaps in the literature: (1) characterize the spectrum of sleep disorders in a well-described sample of myofascial TMD patients, using polysomnography and state-of-the art structured diagnostic interviews; and (2) evaluate possible associations between observed sleep disorder indices and laboratory measures of pain threshold. We hypothesized that rates of primary insomnia would be substantive in TMD and that primary insomnia would be associated with reductions in pain threshold at both masseter and extracranial sites.

Banking sleep: realization of benefits during subsequent sleep restriction and recovery.

Abstract: AMERICAN ADULTS REPORT SLEEPING AN AVERAGE OF 6.8 HOURS ON WEEKNIGHTS1—CONSIDERABLY LESS THAN THE 8 H OF SLEEP THOUGHT TO BE necessary to restore and sustain optimal daytime alertness. However, despite its near-ubiquitousness, chronic sleep restriction has not been scientifically studied to the same extent as acute, total sleep deprivation. In part, this has most likely been due to (a) the relative logistical difficulties associated with studying chronic sleep restriction in a controlled manner, and (b) an implicit, parsimonious assumption that the effects of chronic sleep restriction are qualitatively identical to those of acute total sleep deprivation, differing only in terms of the rate at which the deficits accrue. In previous studies of chronic sleep restriction (≥ 7 consecutive nights) it has been shown that performance and alertness are degraded in a dose-dependent manner.2,3 Also apparent in both studies were (a) substantial individual differences in performance during (resilience to) sleep restriction, and (b) a failure for some aspects of performance to be restored to baseline levels after 3 nights of recovery sleep (with 8 h time in bed per night). Extrapolating from total sleep deprivation studies,4–6 this amount of recovery sleep may not have been sufficient for full recovery, but still was anticipated to produce greater levels of performance improvement than what was observed. Instead, this finding suggested the intriguing possibility that the neurobiological mechanism(s) underlying performance and alertness vary as a function of (and perhaps adapt to) habitual, nightly sleep duration, and that such changes have a relatively long time constant—requiring multiple (e.g., 7) days of continuously elevated sleep pressure (i.e., a longer duration than would typically be imposed in a formal total sleep deprivation study or be manifested in nature as a result of exposure to stressors). Consistent with the possibility of a slow-to-adapt physiological mechanism that mediates alertness and performance, cross-study comparisons of results from some other of our studies7,8 were also consistent with the possibility that recovery rate following multiple days of sleep restriction varies as a function of prior, habitual sleep duration: during which full recovery occurred in volunteers after 2 nights of 8 h time in bed (TIB) when sleep restriction was preceded by 1 week of self-reported TIB of 10 h/night. Therefore, the present study was conducted to systematically determine the effects of prior sleep history on rates of performance and alertness degradation during chronic (7 nights) sleep restriction and during the subsequent recovery period. Specifically, it was predicted that “banking extra sleep” by extending nightly TIB would confer protective benefits during subsequent sleep restriction and facilitate recovery from that sleep restriction.

A review of the effects of sleep during the first year of life on cognitive, psychomotor, and temperament development.

Abstract: During the first year of life, infants spend most of their time in the sleeping state. Assessment of sleep during infancy presents an opportunity to study the impact of sleep on the maturation of the central nervous system (CNS), overall functioning, and future cognitive, psychomotor, and temperament development. To assess what is currently known regarding sleep during infancy and its effects on cognitive, psychomotor, and temperament development, we assessed the relevant literature published over the last several decades. To provide a foundation for a more in-depth understanding of this literature, we preface this with an overview of brain maturation, sleep development, and various assessment tools of both sleep and development during this unique period. At present, we do not have sufficient data to conclude that a causal relationship exists between infant sleep and cognitive, psychomotor, and temperament development. Caution should be used in predicting outcomes, as the timing and subjectivity of evaluations may obviate accurate assessment. Collectively, studies assess a wide array of sleep measures, and findings from one developmental period cannot be generalized readily to other developmental periods. Future studies should follow patients longitudinally. Additionally, refinements of existing assessment tools would be useful. In view of the relatively high reported pediatric prevalence of cognitive and behavioral deficits that carry significant long-term costs to individuals and society, early screening of sleep-related issues may be a useful tool to guide targeted prevention and early intervention.

Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy

Abstract: STANDARD NOSOLOGY CLASSIFIES PATIENTS WHO HAVE SHORT SLEEP LATENCY AND ≥ 2 SLEEP ONSET REM SLEEP PERIODS ON THE MULTIPLE SLEEP LATENCY test as narcoleptic1 Under this definition, more than a quarter of those classified as narcoleptic do not have cataplexy2,3 The intensity of cataplexy in patients classified as having narcolepsy with cataplexy varies greatly: it is the most debilitating symptom in a few patients, causing total loss of muscle tone and consequent collapse several times a day; it occurs rarely and causes only transient weakness of the facial musculature in others4 Narcolepsy with cataplexy has been shown to be characterized by a loss of the hypocretin (orexin) peptide and of the cells generating this peptide5–8 All human narcoleptic brains we have examined have some surviving hypocretin cells with approximately normal morphology9 Unfortunately, collection of the brains of human narcoleptics has been largely limited to patients with cataplexy We now present data from an analysis of the complete hypothalamus of one patient with narcolepsy without cataplexy (patient 1), data from a second narcolepsy without cataplexy patient from which we received only anterior hypothalamic tissue (patient 2), 5 narcolepsy with cataplexy patients, and 6 normal individuals

Logging on for better sleep: RCT of the effectiveness of online treatment for insomnia.

Abstract: Study Objectives: Despite effective cognitive behavioral treatments for chronic insomnia, such treatments are underutilized.1,2 This study evaluated the impact of a 5-week, online treatment for insomnia.

Idiopathic hypersomnia with and without long sleep time: a controlled series of 75 patients.

Abstract: OBJECTIVE: To characterize the clinical, psychological, and sleep pattern of idiopathic hypersomnia with and without long sleep time, and provide normative values for 24-hour polysomnography. SETTING: University Hospital. DESIGN: Controlled, prospective cohort. PARTICIPANTS: 75 consecutive patients (aged 34 +/- 12 y) with idiopathic hypersomnia and 30 healthy matched controls. INTERVENTION: Patients and controls underwent during 48 hours a face-to-face interview, questionnaires, human leukocyte antigen genotype, a night polysomnography and multiple sleep latency test (MSLT), followed by 24-h ad libitum sleep monitoring. RESULTS: Hypersomniacs had more fatigue, higher anxiety and depression scores, and more frequent hypnagogic hallucinations (24%), sleep paralysis (28%), sleep drunkenness (36%), and unrefreshing naps (46%) than controls. They were more frequently evening types. DQB1*0602 genotype was similarly found in hypersomniacs (24.2%) and controls (19.2%). Hypersomniacs had more frequent slow wave sleep after 06:00 than controls. During 24-h polysomnography, the 95% confidence interval for total sleep time was 493-558 min in controls, versus 672-718 min in hypersomniacs. There were 40 hypersomniacs with and 35 hypersomniacs without long ( > 600 min) sleep time. The hypersomniacs with long sleep time were younger (29 +/- 10 vs 40 +/- 13 y, P = 0.0002), slimmer (body mass index: 26 +/- 5 vs 23 +/- 4 kg/m2; P = 0.005), and had lower Horne-Ostberg scores and higher sleep efficiencies than those without long sleep time. MSLT latencies were normal (> 8 min) in 71% hypersomniacs with long sleep time. CONCLUSIONS: Hypersomnia, especially with long sleep time, is frequently associated with evening chronotype and young age. It is inadequately diagnosed using MSLT.

The direction of longitudinal associations between sleep problems and depression symptoms: a study of twins aged 8 and 10 years.

Abstract: Study Objectives: To establish the direction and etiology of longitudinal associations between sleep problems and depression symptoms in children. Design: Data on twins aged 8 and 10 years were obtained. At assessments, parents completed the Child Sleep Habits Questionnaire, and twins completed the Children's Depression Inventory. Setting: Participants were mainly interviewed at the Institute of Psychiatry, London. Patients or Participants: Three hundred twin pairs initially enrolled in the study. Interventions: N/A. Measurements and Results: A genetically informative cross-lagged model examined links between sleep and depression. Sleep problems at age 8 predicted depression at age 10 (partial regression coefficient [95% confidence intervals] = 0.10 [0.01-0.18]). The converse was not found. Stability of sleep problems across time was mainly due to genes (46% of the genetic influence on sleep at 10 was due to the same genetic influence on sleep aged 8). Stability of depression was mainly due to nonshared environmental influences (19% of the nonshared environmental influence on depression at 10 was due to the same nonshared environmental influence on depression at age 8). The cross-lagged association between sleep problems at 8 and depression at 10 years was largely due to genes, although this finding was nonsignificant. Conclusions: This study adds to our understanding of the temporal precedence of sleep problems and depression and the risks underlying their associations. There are implications regarding the value of specifying genes linked to sleep problems and potential opportunities for informing early intervention strategies in high-risk groups at key points in the progression to developing more serious problems.

NREM arousal parasomnias and their distinction from nocturnal frontal lobe epilepsy: a video EEG analysis.

Abstract: Thus, while the broad behavioral characteristics of parasomnias are accepted, surprisingly little detail of their ictal manifestations is known.In this study we have compiled a video-EEG monitoring se-ries with the aim of accurately describing the semiological fea-tures of the NREM arousal parasomnias. In addition we have directly compared these with NFLE, providing an evidence base for the accurate diagnosis of these disorders on semiologi-cal grounds. This knowledge is important for the increasingly common clinical situation of diagnosing attacks recorded by family members on home videos or mobile phone cameras.

Gender Differences in the Cross-Sectional Relationships Between Sleep Duration and Markers of Inflammation: Whitehall II Study

Abstract: SLEEP DEPRIVATION ARISING THROUGH SLEEP DISTURBANCES OR THROUGH VOLUNTARY SHORTENED SLEEP IS ASSOCIATED WITH A NUMBER OF HEALTH outcomes, including cardiovascular disease.1–13 A number of studies in humans have indicated possible pathophysiologic mechanisms to support the biologic plausibility of an association between sleep deprivation and cardiovascular risk.14–17 Acute curtailments of sleep may induce an overactivity of the sympathetic nervous system, leading to increased blood pressure.18–20 Other contributing mechanisms may include overactivity of the renin-angiotensin-aldosterone system, proinflammatory responses, endothelial dysfunction, and renal impairment.14,21 However, it is also plausible that sleep habits may represent a marker of health status and quality of life rather than being a causal factor for many health outcomes. Inflammatory mechanisms are important in the development of cardiovascular disease. Furthermore, short-term sleep-deprivation studies have shown that inflammatory markers are elevated in sleep-deprived individuals, suggesting that inflammatory mechanisms may play a role in the cardiovascular risk associated with sleep deprivation.14–16 The concentration of high-sensitivity C-reactive protein (hs-CRP), a nonspecific marker of acute-phase inflammatory response, is predictive of future cardiovascular morbidity,22 and the relationship of interleukin-6 (IL-6) to coronary heart disease is similar to that of CRP and coronary heart disease.23 Moreover, biologic variability of IL-6 is twice as high as that of hs-CRP, and, after correction for this, the association with coronary heart disease is stronger.23 However, although hs-CRP is elevated following both acute total and short-term partial sleep deprivation,24 a recent study failed to demonstrate any significant association between hs-CRP levels and sleep duration in a combined study of men and women.25 In the present analysis, we sought to examine the relationship between both hs-CRP and IL-6 and sleep duration in the Whitehall II Study. We have conducted gender-specific analyses with the inclusion of a number of potential confounding variables. This is because studies indicate that durations of sleep might be associated with detrimental effects on cardiovascular outcomes among women1–4: moreover hs-CRP levels are elevated in women,26 and gender differences in other inflammatory markers have been reported.27

Evaluation of a School-Based Intervention for Adolescent Sleep Problems

Abstract: DURING ADOLESCENCE THE DISCREPANCY BETWEEN SCHOOL NIGHT SLEEP AND WEEKEND SLEEP GROWS MARKEDLY WITH AGE.1 NUMEROUS STUDIES across cultures have demonstrated adolescent sleep practices lead to later bedtimes and subsequent inadequate sleep on school nights because of forced rise times.1–4 This ongoing pattern of inadequate sleep on school nights influences adolescent sleep behavior on weekends, with delayed rise times allowing for an increase in total amount of sleep on weekends.1,3–5 The delay in adolescent sleep onset and offset has historically been attributed to psychosocial factors.1 However, persistence of the sleep delay occurs due to underlying biologic regulatory processes that appear to change significantly from childhood to adolescence.1,6,7 The combination of delayed bedtime on weekends and sleeping-in on weekend mornings also results in a delay of the sleep circadian rhythm in and of itself.8,9 With growing evidence that chronic inadequate sleep results in negative daytime consequences (e.g., daytime sleepiness, depressed mood),10,11 interventions designed to reverse adolescent delayed sleep timing may help alleviate these problems.12 Treatment of sleep problems in adults generally consist of a combination of behavioral and cognitive strategies, and to date, treatment of adolescent sleep problems largely rely on the adaptation of successful treatment methods used with adults.12,13 Comprehensive treatments are likely to include combinations of sleep hygiene education,14 including the regularization of bedtime/waketime routine across the week15; early morning bright light exposure16,17; stimulus control therapy18; and cognitive therapy to address unhelpful sleep beliefs.19 In exceptional circumstances, psychopharmacological treatments are used but are not recommended until behavioral and cognitive treatments have been exhausted.19 However, despite the fact that cognitive-behavioral strategies have extensive empirical support for adults, support for their application to adolescent sleep problems is limited. Despite the potential benefit of treatment, screening is rare for sleep problems in adolescents in primary healthcare settings.20 In addition, the existing literature indicates that adolescents who do attend therapy for sleep problems show inconsistent treatment attendance, high dropout rates, poor treatment adherence, and variable motivation.12 Thus, novel methods, such as school-based sleep education programs, have potential to circumvent such problems. The benefits of school-based prevention programs have been demonstrated for a variety of disorders.21–23 Although largely untested in the area of sleep, recent studies exploring the effectiveness of school-based sleep interventions have shown promise.24–26 However, these programs have largely focused on promoting good sleep hygiene despite the observation that empirical evidence for sleep hygiene as the sole treatment is limited.27 Other limitations, including selection bias (given low response rates, e.g. 44.5%), a lack of control group comparison,26 small sample sizes, compliance issues, and lack of follow-up data,24,25 suggest the need for improved implementation and evaluation of such programs in schools. Researchers in other fields (e.g., drug prevention) have noted that acquisition of knowledge is rarely enough in itself to change behavior.28 However, interactive, multisession prevention programs that encourage student participation have been shown to be more effective than brief didactic programs (e.g., < 3 lecture-style classes) in changing target behavior28–30 due to higher levels of student engagement facilitating application of new knowledge, as well as attitudinal and behavioral change.28–30 The present study was developed to evaluate a controlled, interactive, multi-session, school-based sleep intervention for senior secondary students (mean age = 15.6 ± 0.6 y), particularly for those adolescents with a delay in their sleep timing. The study's aims were to (1) increase sleep knowledge, and (2) effect a change in behavior that would improve sleep parameters (e.g., sleep latency, total sleep time, regularize bedtimes), and associated improvements in daytime functioning (e.g., daytime sleepiness, depressed mood).