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Sleep problems are extremely common during childhood, from infancy to adolescence. Despite the prevalence of sleep problems, childhood sleep disorders are often underrecognized and undiagnosed, despite being either preventable or treatable. Sleep impacts almost all aspects of a child's functioning, and thus the increased recognition and treatment of sleep disorders will positively affect a child's well-being. Children experience the same broad range of sleep disturbances encountered in adults, including sleep apnea, insomnia, parasomnia, delayed sleep phase, narcolepsy, and restless legs, but their clinical presentation, evaluation, and management may differ. Although snoring and sleep apnea may be the most common indication for an overnight sleep study in a child, one quarter of children presenting to a sleep clinic for evaluation will have a second sleep diagnosis, which is often nonrespiratory in nature. Especially in children, ruling out sleep apnea is rarely the end point of the sleep evaluation. Clinicians involved in sleep medicine must be prepared to recognize, evaluate, and manage plans for sleep disorders across the lifespan of the patient. This article will provide an updated review of nonrespiratory pediatric sleep disorders within a developmental framework.

Abnormal sleepiness is one of the primary symptoms of sleep disorders. Sleepiness is a normal physiologic phenomenon, however, and only becomes excessive when it occurs in situations when individuals can be reasonably expected to be awake and alert [1]. The degree of sleepiness depends on interplay between two factors: the time in the circadian cycle (process C), and the length of time from the last sleep period (process S) [2]. In subjects with normal circadian rhythmicity, sleepiness is maximal between 2 and 6 AM with a second minor peak 12 hours earlier in the afternoon. This rhythm is modified by the degree of accumulated sleep debt, a process that results in a homeostatic drive to induce sleep. Sleepiness is counterbalanced by alerting mechanisms, modulated predominantly by monoaminergic neuronal systems, such as dopaminergic and histaminergic pathways. The cluster of hypocretin (orexin) secreting neurons in the hypothalamus may be the master controller modulating monoaminergic systems, with projections from these neurons being widely distributed to the brainstem, diencephalon, and basal forebrain [3]. Sleepiness can be conceptualized as having two components: the subjective perception of the need to sleep, and the ability to transition from a state of wakefulness to a state of sleep [4]. The perception of the need to sleep is usually accompanied by objective manifestations, such as yawning, loss of neck extensor tone, pupillary constriction, ptosis, and a decreased attention span. The ability to fall asleep can be measured objectively using electroencephalographic activity and this forms the basis for the Multiple Sleep Latency Test (MSLT). The two components of sleepiness may dissociate; some patients with pathologic sleepiness have little or no warning of sleep onset, whereas patients with restless legs syndrome or psychophysiologic insomnia may have an intense desire to fall asleep but be unable to do so. Excessive sleepiness may be caused by factors that disrupt circadian rhythmicity, increase sleep debt by either voluntary curtailment of sleep time or fragmentation of sleep, or decrease the drive toward alertness [Box 1] [4]. Disorders of circadian rhythmicity include intrinsic disorders, such as delayed sleep phase syndrome, and extrinsic causes, such as the effects of shift work. Insufficient sleep syndrome, perhaps the commonest cause of excessive sleepiness, is caused by voluntary sleep curtailment. Fragmentation of sleep by diseases, such as obstructive sleep apnea syndrome, or environmental factors, such as exposure to a bed partner’s snoring [5], reduce the restorative value of sleep and increase sleep debt. Narcolepsy, in association with cataplexy, is caused by reduced activity of the wakefulness system secondary to decreased hypocretin production. Histamine receptor antagonists reduce alertness, as do benzodiazepine receptor agonists, such as benzodiazepines, barbiturates, and alcohol.

The most frequent sleep problems are sleep-related breathing disorders, insomnia, excessive daytime sleepiness, and circadian rhythm disorder. In 2004, we treated 468 sleep disorder patients, at the Sleep Disorder Center, Shiga University of Medical Science Hospital. Forty-nine percent of the subjects were diagnosed as having sleep related breathing disorders, 22% as insomnia, 10% as rhythm disorders and 5% as having excessive daytime sleepiness. Insomnia is a common sleep-wake-related complaint, and sleeping pills are among the most commonly prescribed drugs in clinical practice. However, insomnia is a symptom that can be caused by various disorder's, many of which require specific therapies. One specific cause of insomnia in older adults is restless legs syndrome. This condition, characterized by an urge to move the legs, which is usually accompanied by sensations of discomfort and aggravations of symptoms by rest. Daytime sleepiness is a common complaint. Snoring, the use of hypnotic agents, sleep difficulties, irregular sleep-wake schedule and sleep deprivation are related to daytime sleepiness. Circadian rhythm sleep disorders have intrinsic and extrinsic subtypes: delayed sleep phase syndrome, advanced sleep phase syndrome and non-24-h sleep-wake syndrome. The underlying problem of circadian rhythm sleep disorders is that the patient cannot sleep when sleep is desired. Waking episodes may occur at inappropriate times; therefore, the patient may complain of insomnia or excessive sleepiness.

Idiopathic chronic sleep onset insomnia (SOI) in children with Attention-Deficit/Hyperactivity Disorder (ADHD) shows typical characteristics of the delayed sleep phase syndrome and could, therefore, be considered a circadian rhythm sleep disorder. A variable number tandem repeat (VNTR) polymorphism of the clock gene PER3 is associated with the delayed sleep phase syndrome and, hence, may associate with ADHD-related chronic SOI as well. Here, we investigated an association between ADHD-related chronic SOI and the VNTR polymorphism of PER3 in 10 medication naive children with rigorously diagnosed ADHD and SOI (ADHD-SOI), and in 10 normal controls. Actigraphic sleep onset and sleep duration and salivary dim light melatonin onset (DLMO) were evaluated in ADHD-SOI. The 4-repeat allele frequency was lower in ADHD-SOI (0.65) than in normal controls (0.75) ( p =0.73) with an odds ratio of 0.62 (CI 0.16-2.4). In ADHD-SOI, mean (SD) DLMO (21:380:50 h), sleep onset (22:170:46 h), and sleep duration (9:260:41 h) were not significantly related to the 4-repeat allele frequency. The present findings suggest no association between ADHD-related idiopathic chronic sleep onset insomnia and the PER3 VNTR polymorphism.

Oral melatonin supplementation has been heralded as a treatment for the sleep disorders of delayed sleep phase syndrome (DSPS) and primary insomnia (PI) in adults (18 to 65 years). However, there is inconsistency in the literature and many of the claims for melatonin appear to be based upon its effect in older adults ( > 65 years). This article reviews, systematically, studies of oral melatonin in adults (18 to 65 years) with either delayed sleep phase syndrome (DSPS) or primary insomnia (PI). Following electronic database searching, and hand-searching of relevant journal titles, fourteen articles that examined the use of melatonin in adults with PI or DSPS were identified for inclusion in this review (eight for DSPS and four for PI). Generally, the quality of articles is limited, particularly with regard to reporting of sleep parameters. However, results indicate that melatonin may phase-advance the sleep of individuals diagnosed with DSPS, although the majority of this evidence comes from uncontrolled trials. There is little evidence to suggest that melatonin is an effective treatment for PI. Further research, addressing deficiencies in the current literature, and considering long-term efficacy and safety are necessary before definitive conclusions as to the value of oral melatonin can be drawn.

This paper presents a comprehensive review of delayed sleep phase syndrome (DSPS), a circadian-rhythm sleep disorder thought to result from the endogenous circadian pacemaker being "stuck" at a later-than-normal phase, relative to the desired sleep-wake schedule. A full understanding of this disorder is best appreciated from the context of shared modulation of sleep and wakefulness via sleep homeostatic and circadian systems. Typically emerging during adolescence, DSPS comes to clinical attention much less often than prevalence estimates would suggest, perhaps due to underrecognition by clinicians and misattribution of symptoms. Several treatment modalities have been suggested, including phototherapy, chronotherapy, and exogenous melatonin administration. However, caution is raised for the reason that more than 20 years after its initial description in the literature, the basic pathophysiology of DSPS remains poorly understood, as observed in the 2003 National Sleep Disorders Research Plan. Challenges for future research include elucidating the exact sleep homeostatic and circadian contributions to the disorder, improving the objective verification of this diagnosis instead of relying only on self-report information, and conducting treatment research aimed at determining efficacy, effectiveness, and mechanism or mechanisms of action.

Recent studies have shown that functional variations in clock genes, which generate circadian rhythms through interactive positive/negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIepsilon), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIepsilon induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIepsilon gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIepsilon. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIepsilon with the S408N variation was approximately 1.8-fold more active than wild-type CKIepsilon. These results indicate that the N408 allele in CKIepsilon plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

Chronobiological disorders and syndromes include seasonal affective disorder (SAD), total blindness, advanced and delayed sleep phase syndrome, jet lag, and shift work maladaptation. These disorders are treated by adjusting circadian phase, using appropriately timed bright light exposure and melatonin administration (at doses of 0.5 mg or less). In some cases, it may be necessary to measure internal circadian phase, using the time when endogenous melatonin levels rise.

Delayed sleep phase syndrome (DSPS) is a chronic sleep onset insomnia that is caused by a persistent delay of sleep timing. Functional abnormalities of the circadian pacemaker have been assumed to underlie this syndrome, but its detailed pathophysiology has not yet been identified. We studied nine patients with DSPS and 20 healthy controls to compare habitual sleep timings and hormonal rhythms between the groups. Concentrations of serum melatonin, cortisol, and thyroid-stimulating hormone (TSH) were assessed every hour for 26 h under dim light condition. The hormonal rhythms were significantly delayed in patients with DSPS compared with controls, whereas the 24-h amounts of hormonal secretions and the phase relationships between the hormonal rhythms did not differ between the groups. We postulate that sleep-phase delay in patients with DSPS is a consequence of the phase delay of the circadian pacemaker, therefore, suggesting that phase delay in the circadian clock is responsible for this disorder.

Study objectives The objective of this study was to clarify sleep characteristics and pathophysiology in patients with delayed sleep phase syndrome (DSPS), which is a major circadian rhythm sleep disorder subtype. Design Polysomnography was performed for 2 consecutive nights and core body temperature was sampled for 7 consecutive days, including the polysomnography study period, in all subjects. Findings were compared and statistically analyzed between patients with DSPS and matched controls. Setting Sleep disorders unit in National Center Hospital. Participants 11 DSPS patients and 11 age-matched healthy volunteers. Interventions N/A. Measurements and results Sleep latency, total sleep time, wakefulness after sleep-onset, and the amount and percentage of Stage 1 sleep were greater in DSPS patients than in volunteers. Sleep efficiency and the amount and percentage of slow wave sleep were lower in DSPS patients than in volunteers. Compared with the healthy volunteers, DSPS patients showed a decreased number and different temporal distribution of high-voltage and low-frequency delta waves. The time of minimum body temperature appeared earlier in the sleep phase for the patients than for the volunteers. Significant correlation was found between the amount of slow wave sleep and the time from sleep onset to minimum body temperature and between the amount and percentage of slow wave sleep and time from minimum body temperature to sleep offset. Conclusions Disturbances were found in the sleep structure of patients with DSPS, and these disturbances were related to the discrepancy between patients and controls in the phase relationship difference between sleep and core body temperature rhythms.

It is common practice to forcibly awaken patients from an all-night polysomnographic study prior to performance of a multiple sleep latency test (MSLT); either for reasons of protocol or for the convenience of the laboratory personnel. We report a case of a young woman who, by formal sleep study criteria, received the erroneous diagnosis of narcolepsy due to the effects of severe sleep deprivation, and document that the effects of prior sleep deprivation require more than one night of ad libitum sleep. Forced awakening prior to MSLT may permit sleep deprivation or delayed sleep phase syndrome to masquerade as narcolepsy or idiopathic central nervous system (CNS) hypersomnia.

Sleep disorders are relevant to psychiatric practice in a number of ways, including the possibility that they may be misdiagnosed as fundamentally psychiatric conditions in patients of all ages. This risk exists in a wide range of collectively very common sleep disorders which need to be considered in explaining insomnia, excessive sleepiness or disturbed episodes of behaviour associated with sleep (parasomnias). Examples given include circadian sleep–wake cycle disorders (such as the delayed sleep phase syndrome), obstructive sleep apnoea, narcolepsy, Kleine–Levin syndrome, sleep paralysis and rapid eye movement (REM) sleep behaviour disorder. Failure to recognise and treat such disorders is likely to cause and perpetuate psychological problems. Correct recognition requires familiarity with the range and manifestations of sleep disorders.

Eating disorders and school refusal behavior with delayed sleep phase are pathologies associated with very different or even inverse school problems. It is through these two prisms that we will develop the idea of school care, which is being set up in the innovative framework of the Mediterranean Area of the Adolescent, integrating a National Education Unit within the Child and Adolescent Psychiatry unit. This specific care seems to us interesting in the adolescent because it allows a work in «natural» environment of certain difficulties related to the different psychiatric disorders and seems to us as a help to the revival of the adolescent process.

Sleep disorders are of increasing importance in the society and this is due to many reasons. Firstly, sleep disorder/disturbance in the young can have psychosocial consequences with an impact on education, work, and mental health, and may also underpin unemployment. One may suspect that the use of social media and nightly entertainment in young subjects may blur the clinical picture, and sometimes hinder a diagnosis of a real sleep disorder. Secondly, the impact of sleep disturbances is increasingly focused in the society with regard to traffic safety questions, where accidents can be related to reduced mental concentration due to sleepiness (1). Finally, the impact of sleep disturbance on the general outcome of a variety of diseases is increasingly highlighted, like for example in epilepsy, Alzheimer’s, and Parkinson’s disease (2). Sleep disorders can be hard to diagnose: they often have an onset in young ages, but young people are on the other hand also prone to a physiological sleepiness or delayed sleep phase, sometimes facilitated by the use of social media and nightly entertainment. The latter circumstances can hinder the diagnosing, which sometimes is difficult and needs laboratory support (3). In addition, the young cases with narcolepsy due to the Pandemrix vaccination against swine flu in Europe in 2009/2010 indeed put a focus on sleep disorders as a whole, with increasing awareness among physicians but also in the society, and an increasing research activity (4–6). This situation indicated clearly that narcolepsy is an autoimmune disease and in fact recent research has clarified the pathology to a big extent: the experience with the Pandemrix/H1N1-initiated cases gave evidence that there is a combined pathogenesis with a genetic component (HLA DQB1*0602) and an environmental factor like vaccination/virus working through molecular mimicry. The harmed site is a neuronal locus in the lateral hypothalamus, where hypocretin-producing cells are severely affected. The etiology and mechanisms of other sleep disorders like, for example, hypersomnias are far more unclear. The rare form of periodic hypersomnia, the Kleine–Levin syndrome (KLS), is important to recognize, since it can be mixed up with physiological sleepiness in teenagers or psychiatric conditions, again pointing at the importance of a proper differential diagnosing (3, 7–9). Another condition of particular interest for the young is the delayed sleep phase syndrome (DSPS) (3). Finally, in many countries, there is increasing interest to detect and treat the obstructive sleep apnea syndrome (OSAS), since it is a condition with substantial impact on the occupational life and also with severe cardiovascular risks in the long run (10). This research topic specifically aims at describing the progress of imaging sciences in sleep medicine. It is a rapidly developing instrument, both regarding pathological and physiological conditions in humans. Today’s knowledge of sleep physiology is founded on observations that are about 100 years old: the key components of the sleep–wake regulatory systems originates from von Economo’s studies on a specific hypersomnia disorder, encephalitis lethargica. Already in the early twentieth century, von Economy identified the specific areas of the brain where lesions caused abnormal sleep–wake behavior. Quite recently, these discoveries have been actualized and more details of the brain circuitries and the neurotransmitters involved in sleep–wake regulation have been described. Nevertheless, the neural substrates that regulate our diurnal regulation of sleep and wakefulness are not yet completely understood. Here, Larson-Prior and co-workers review the present knowledge about brain circuits involved in sleep and sleep disorders (11). In addition, the authors address the important relation between sleep and cognition. Sleep disorders can provide novel insights into the brain’s sleep–wake regulatory systems. Narcolepsy, which is characterized by sudden sleep attacks that can appear several times a day, is related to loss of hypocretin-producing neurons in the hypothalamus. The hypothalamus is one important node of one of the two major branches of the ascending arousal system. The other branch involves the thalamus, which might be affected in KLS. In a perspective article, Engstrom et al. suggest that functional magnetic resonance imaging (fMRI) can identify anatomical biomarkers of brain function related to narcolepsy and KLS and their concomitant symptoms (12). An interesting example is given in the case study that shows reduced thalamic and pontine connectivity during a hypersomnia period in KLS (13). A possible diagnostic method, single photon emission computed tomography (SPECT), is evaluated in the article by Vigren et al. (14). Neural circuits involved in sleep disorders could also be studied by pharmacological interventions. Sveinsson discusses this topic in his case study on lithium treatment in KLS (15), and Sarkanen and co-workers report on psychosis in narcolepsy patients treated by sodium oxybate (16). Another intervention, continuous positive airway pressure (CPAP) in OSAS, is reviewed by Huynh and co-workers, interestingly using a radiological volumetric outcome (17). A general clinical background is sketched in The Sleepy Teenager by Landtblom and Engstrom (3), aiming at building a structure for efficient diagnosing. Finally, a book review of Neuroimaging of Sleep and Sleep Disorders (18) concerning imaging methods in sleep medicine highlights the evolving investigation possibilities, from clinical and research aspects. This is a volume that we do recommend as a guide and inspiration.

Sleep diaries are valuable tools in assessing sleepless or restless patients (Fig. 9.1a). A sleep diary is designed to get the information about a patient’s sleep pattern. It has the potential of reducing recall or report bias. The patient self-monitors his/her sleep every night and records it. This helps in the initial assessment as well as in tracking treatment effect of different interventions. Actigraphy utilizes a wristwatch-like portable device which contains an accelerometer, a clock, internal memory, and a photo sensor. It records the rest/activity cycle which may correspond to the sleep/wake cycle. It may assist to determine the sleep patterns in normal healthy adult population, to evaluate patients suspected of advanced sleep phase syndrome (ASPS), delayed sleep phase syndrome (DSPS), shift work sleep disorder, and other circadian sleep disorders including jet lag and non-24 h sleep/wake syndrome. It is used to determine the circadian rhythm patterns in patients with insomnia (including insomnia associated with depression) and hypersomnia.

A change in sleep patterns often accompanies the onset of adolescence. Declining parental involvement in bedtime routines, increasing academic pressure, emergence of several distracters such as social media, Internet, electronic gadgets and cell phones have contributed in the shift towards later bedtimes from pre-adolescent to adolescent years. As a result, sleep debt accumulates over time leading to sleep deprivation which can have disastrous consequences on the physical, emotional and cognitive functioning of the individual. Chronic sleep deprivation leads to insufficient sleep which is major sleep problem faced by adolescents today. Sleep assessment is done using subjective and objective methods. Subjective methods include clinical sleep history taking which include physical examination, psychosocial history, interviews regarding bedtime routines and nocturnal behaviour. Several parent rated and self-rated questionnaires are also used for screening sleep disorders such as sleep-related breathing difficulties, restless legs syndrome, delayed sleep phase syndrome and narcolepsy. Objective methods include sleep diaries/sleep logs, actigraphy, polysomnography and multiple sleep latency tests. Early intervention at the school level (pre-adolescent stage) is important for inculcating healthy sleep habits. Sleep education during early years can help prevention of sleep problems as many of these problems are maintained due to maladaptive sleep hygiene practises. This chapter focuses on adolescent sleep struggles specifically insufficient sleep and discusses intervention strategies which include sleep education, stimulus control and sleep hygiene, troubleshooting adolescent’s difficulties in adhering to treatment guidelines, barriers to treatment followed by conclusions and future directions.

Background: Sleep disturbance is a prevalent and clinically significant feature of bipolar disorder. However, there are aspects of sleep and bipolar disorder that have been minimally characterized. This study aims to fill several gaps in the literature by examining the prevalence, coexistence, and persistence of sleep disturbance retrospectively across a five-year period in bipolar disorder. Methods: Fifty-one people with bipolar disorder I and comorbid insomnia who were currently inter-episode completed the NIMH Retrospective Life-Charting Methodology (the life chart). The life chart was used to document the prevalence, coexistence, and persistence of insomnia, hypersomnia, delayed sleep phase, reduced sleep need, and irregular sleep patterns across the course of five years. Results: Across the five year period, manic months were primarily characterized by reduced sleep need (62.8%) and insomnia (38.1%), depressive months by hypersomnia (56.0%) and insomnia (51.9%), mixed months by all five types of sleep disturbance, and inter-episode months by insomnia (67.4%). There was coexistence in the types of sleep disturbance experienced. Further, each type of sleep disturbance demonstrated persistence across the five years, with persistence rates being the highest for insomnia (49.0–58.8%). Conclusions: Sleep disturbance is a prevalent and complex feature across mood episodes and inter-episode periods of bipolar disorder. Further, there is variation in the types of sleep disturbance experienced.

Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3�-untranslated region (3�-UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (I�) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne-A�stberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and I�, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3�-UTR were transfected into COS-1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, I�, or delayed sleep phase syndrome in humans.

The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.

We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that provides light through closed eyelids during sleep. Volunteers received either bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26) for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising, ramped up for 1 h, and remained on at full brightness until arising. Volunteers also attempted to systematically advance sleep time, avoid naps, and avoid evening bright light. The light mask was well tolerated and produced little sleep disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion advanced significantly from baseline in the bright group ( p < 0.0006) and not in the dim group, but final phases were not significantly earlier in the bright group (ANCOVA ns). Bright treatment did produce significantly earlier phases, however, among volunteers whose baseline 6-SMT acrophase was later than the median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h, ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p < 0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment ( p < 0.04). We conclude that bright-light mask treatment advances circadian phase and provides clinical benefit in DSPS individuals whose initial circadian delay is relatively severe.

Medical Outcome Study Short Form-36 (MOS SF-36) qualities of life scores were studied in 38 chronic fatigue patients with late melatonin onset before and after treatment with melatonin. Before start of the treatment, quality of life was assessed twice. Pre-treatment scores were compared with each other and with the scores of 43 patients with Delayed Sleep Phase Syndrome and of 1063 healthy subjects. Melatonin, 5 mg, was taken orally, 5 hours before baseline salivary endogenous dim light melatonin onset.After mean (SD) treatment of 13.7 (0.8) weeks, quality of life scores “physical functioning,” “energy/vitality,” “bodily pain,” and “general health perception” improved (p values, respectively, 0.017, 0.002, 0.002 and 0.009). In the pre-treatment period (mean [SD] interval: 6.5 [0.6] weeks) “social functioning” and “general health perception” improved (p = 0.013 and 0.010, respectively).In the chronic fatigue patients the quality of life scores did not differ from those of the Delayed Sleep Phase Sy...

The article presents a study on the genetic mutation that affects the circadian clock of insomniacs to cause the delayed sleep phase disorder.

IntroductionCircadian rhythm sleep disorder, free-running type (FRD)occurs primarily in blind persons who are deprived of theentraining effects of light. It is rare in sighted patientsand usually occurs in those who live in environmentswith low light levels and those working unusualschedules [1]. We report a case of a young man withdelayed sleep phase tendency, depression, obstructivesleep apnea (OSA), and near complete lack of socialinteraction who developed FRD.Report of caseA 20-year-old man with history of depression cluster head-achesandgoutpresentedforsleepevaluationduetoexcessivedaytimesleepiness.Hisproblemswithdaytimesleepinessanddelayed sleep onset started at age 12. By age 15, he startedhome schooling due to his problems adjusting with earlyrising. At age 18, he was diagnosed with OSA at an outsideinstitution, with apnea–hypopnea index (AHI) of 17/h at thattime.Sleepefficiencywas83%andanarousalindexwas19/h.He underwent a trial of continuous positive airway pressure(CPAP) therapy; his sleep-disordered breathing was correctedat the pressure of 11 cmH

Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomised, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders. An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep wake syndrome in people who are blind, and rapid eye movement-behaviour disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep. A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomised and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo. These findings highlight the potential importance of melatonin in treating certain first degree sleep disorders. The development of large-scale, randomised, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.

Objectives:The current study aimed to evaluate school-based motivational sleep education programs (SEPs) with adjunct bright light therapy (BLT) and/or parental involvement (PI). Design: Randomized controlled trial. Setting: Six high schools, matched on socio-economic status (SES). Participants: A total of 193 adolescents (mean age, 16.3 ± 0.4 years, 79%f). Intervention: Classes were randomly assigned to (i) SEP + BLT, (ii) SEP + PI, (iii) SEP + BLT + PI, or (iv) classes-as-usual (CAU). Sleep education programs involved 4 × 50 minute classes (over 4 based on a Motivational Interviewing framework (Sleep Med 2011;12:246-251). Students in BLT groups attempted a weekend phase advance using portable green light LED glasses (500 nm; 506 lux). Parents of PI groups watched a series of 4 YouTube clips (2-3 minutes in length) outlining their adolescent's learning in class and how they could assist. Students in the CAU groups continued their regular classes. Measurements: Online questionnaires measuring sleep knowledge, sleep patterns (bedtime, sleep latency, total sleep time [TST], etc) and mood at preintervention and postintervention and 6-week follow-up. Intervention groups also completed a motivation-to-change questionnaire and provided qualitative feedback.Setting: Six high schools, matched on socio-economic status (SES). Results:Improvements in sleep knowledge (d = 0.59-0.88), sleep onset latency (d = 0.45-0.50), TST (d = 0.32-0.57), and mood (d = 0.24-0.46) were observed in all intervention groups relative to the CAU group. Similar improvements were observed in a subgroup of students identified as having delayed sleep timing (ie, sleep knowledge: d = 0.45-0.92; sleep onset latency: d = 0.59-0.82; TST: d = 0.82-1.18). Increases in motivation to regularize out of bedtimes, obtain morning bright light (BLT groups), and avoid sleeping-in on weekends occurred (all P < .005). Conclusions: This motivational SEP produced meaningful and similar benefits for adolescents in all intervention groups. Longer BLT (ie, over school holidays) and more intensive parental inclusion should be investigated in future studies. Refereed/Peer-reviewed

According to classification manuals for sleep disorders, nine disorders are directly related to biological clock timing misalignments. Of all, delayed sleep phase disorder (DSPD) is the most commonly diagnosed, predominantly affecting adolescents, young adults, and insomnia patients. It is a persistent inability to fall asleep at earlier, more desirable and socially conventional times, coupled with extreme difficulty awakening in the morning. Considerable evidence shows a delay in the circadian clock to be associated with DSPD. Therefore, treatments have mainly focused on advancing the biological clock and sleep timing through pharmacotherapy, phototherapy and behavioral therapies. The clinical evidence indicates that these treatments are efficacious, at least in the short term. However, follow up studies show frequent patient relapse, leading researchers to speculate that alternative etiologies may be contributing to sleep and circadian clock delays in DSPD. The aim of the present paper is to review and collate current literature related to DSPD etiology in order to outline gaps in current knowledge and suggest future research.

© 2014 Korean Neuropsychiatric Association. People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness- eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and “eveningness” were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Delayed sleep phase disorder is the most common of the circadian rhythm sleep disorders. Its treatment involves exploiting the intrinsic biological properties of the circadian pacemaker to advance biological rhythms, most notably the sleep-wake cycle, to a time which affords the individual an appropriate sleep opportunity compatible with normal societal functioning. This review highlights several new studies published in the last 18 months concerning sleep and circadian physiology relevant to the disorder and its management.In addition to new information regarding the epidemiology and associations of the disorder, the pathophysiological importance of light exposure across the entire day, with special relevance to the phase-delaying effects of artificial evening light, is being unravelled. Furthermore, disorder-specific differences in period length and sleep homeostasis are being considered as pathophysiological contributors to delayed sleep phase disorder. The molecular effects of chronic sleep deprivation and circadian misalignment are currently being explored as potential mechanistic markers of the deleterious health consequences associated with these states.Advances in our understanding of the dynamics of circadian physiology, sleep-wake regulation and the deleterious effects of misalignment and sleep deprivation, are spurring on efforts to find optimal treatment paradigms for patients presenting to sleep clinics with delayed sleep phase disorder.

Findings of this meta-analysis show that obsessive-compulsive disorder (OCD) is related to disruptions in both the duration and timing of sleep. PsycINFO and Google Scholar database searches identified 12 relevant studies that compared measures of sleep in individuals with OCD to those of either a healthy control group or published norms. Sleep measures included sleep onset latency, sleep duration, awakening after sleep onset, percentage of rapid eye movement (REM) sleep, percentage of slow wave sleep, and prevalence of delayed sleep phase disorder (DSPD). Individual effect sizes were pooled using a random effects model. Sleep duration was found to be shorter, and the prevalence of DSPD higher, in individuals with OCD compared to controls. Further, excluding samples with comorbid depression did not meaningfully reduce the magnitude of these effects (although the results were no longer statistically significant) and medication use by participants is unlikely to have systematically altered sleep timing. Overall, available data suggest that sleep disruption is associated with OCD but further research on both sleep duration and sleep timing in individuals with OCD is needed.

The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

Humans spend a third of their lives asleep. A well-balanced synchrony between sleep and wakefulness is needed to maintain a healthy lifestyle. Optimal sleep is based on an individual's inherent sleep requirement and circadian rhythm. If either one or both of these critical elements are disrupted, daytime dysfunction, non-restorative sleep, and/or reduced sense of well-being may result. While the medical community is more familiar with sleep disorders such as sleep apnea, insomnia, and narcolepsy, circadian rhythm sleep wake disorders (CRSWDs) are less known, despite these being common within the general population. CRSWDs are comprised of the following: shiftwork disorder, delayed sleep phase disorder, advanced sleep phase disorder, jet lag disorder, non-24-hour sleep-wake disorder, and irregular sleep-wake rhythm disorder. In general, a CRSWD results when there is misalignment between the sleep pattern and the desired sleep schedule, dictated by work, family, and social schedules. Subsequently, patients have difficulty falling asleep, maintaining sleep, and/or experience poor quality sleep predisposing them to insomnia or excessive sleepiness. In this article, we review the core concepts related to sleep, and sleep deprivation in the context of CRSWDs.

The aim of the current study was to compare mental health problems, resilience and family characteristics in adolescents with and without delayed sleep phase (DSP) in a population-based sample. Data were taken from the youth@hordaland-survey, a large population-based study in Hordaland County in Norway conducted in 2012. In all, 9338 adolescents aged 16-19 years (53.5% girls) provided self-reported data on a wide range of instruments assessing mental health symptoms, including depression, anxiety, obsessive-compulsive behaviours, attention deficit hyperactive disorder (ADHD) symptoms, perfectionism, resilience and sleep. Measures of socioeconomic status were also included. Three hundred and six adolescents (prevalence 3.3%) were classified as having DSP [according to the International Classification of Sleep Disorders-2 (ICSD-2)] criteria. Adolescents with DSP reported higher levels of depression, anxiety and ADHD symptoms. Adolescents with DSP also exhibited significantly lower levels of resilience. The Cohen's d effect sizes ranged from small [obsessive-compulsive disorder (OCD): d = 0.15] to moderate (inattention: d = 0.71). In the fully adjusted model, the significant predictors of DSP included inattention [odds ratio (OR): 2.11], lack of personal structure (OR: 2.07), low (OR: 1.85) and high (OR: 1.91) paternal education, parents not living together (OR: 1.81), hyperactivity/inattention (OR: 1.71) and poorer family economy (OR: 1.59). In conclusion, the high symptom load across a range of mental health measures suggests that a broad and thorough clinical approach is warranted when adolescents present with DSP.

A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

Objective To examine the effects of changes in sleep phase on the daytime functioning of new university graduates. Methods Questionnaire data of university students ( n = 745) and university graduates working full time ( n = 360) were analyzed to explore sleep phase changes during this life stage. The newly graduated full-time workers ( n = 117) were divided into 2 (bedtime at investigation: earlier/later) × 2 groups (bedtime at one year prior to investigation: earlier/later), and depressive symptoms and health-related quality of life were compared among groups. Results New university graduates experienced ~1 h of sleep phase advancement and shortened time in bed compared to one year before investigation. In addition, those who experienced such sleep changes showed larger daytime dysfunction. Conclusion Prevention of extreme sleep phase delay during university days might be helpful for students' adaptation to work environment after graduation.

Hyperarousal Scale scores for certain self-reported behaviors reportedly correlate with EEG arousal measures. We tested whether an insomnia subject group had different Hyperarousal Scale scores compared with hypersomnia, delayed sleep phase syndrome, procrastinator or normal subject groups. Compared with 139 normal subjects, mean scores for a group of 256 insomnia subjects was significantly 1.2 S.D. higher on Hyperarousal total scale score, 0.82 S.D. higher on React subscale score and 0.85 S.D. higher on Introspectiveness subscale score. The insomnia group median Extreme score was 2.25 times that of the normal group. These self-report findings suggest that insomnia subjects may be more responsive generally. All sleep disorder groups had increased total Hyperarousal scores, although these increases were accounted for by different scale items. The procrastinator group had Hyperarousal score patterns that generally differed from those of the other groups.

Patients with delayed sleep phase syndrome (DSPS) experience a chronic mismatch between the usual daily schedule required by the individual's environment and their circadian sleep-wake pattern, resulting in major academic, work, and social problems. Although functional abnormalities of the circadian pacemaker system have been reported in patients with DSPS, the etiology of DSPS has not been fully elucidated. One hypothesis proposed to explain why patients with DSPS fail to synchronize their 24 h sleep-wake cycle to their environment is that they might have reduced sensitivity to environmental time cues, most notably light-dark cycles. Therefore, we compared the sensitivity of melatonin suppression in response to light in patients with DSPS and normal control subjects. Fifteen patients with DSPS and age- and sex-matched healthy controls were studied. As the melatonin secretion rhythm in patients with DSPS was expected to be delayed compared to the controls, the time of peak melatonin secretion was determined in each subject in the first session. In the second session, each subject was exposed to light with an intensity of 1000 lux for 2 h beginning 2 h prior to his or her peak melatonin secretion. Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutes during the period of light exposure. Suppression of the melatonin concentration in saliva was dependent on duration of light exposure. In addition, the suppressive effect of light on the melatonin concentration was significantly greater in patients with DSPS than in control subjects. The results suggest hypersensitivity to nighttime light exposure in patients with this syndrome. Our findings therefore suggest that evening light restriction is important for preventing patients with DSPS from developing a sleep phase delay.

The prevalence of delayed sleep phase syndrome (DSPS) has been estimated to be quite low. Although no genetic inheritance pattern has been described, it has been reported that close to 50% of DSPS patients have biological relatives with similar symptoms. A pedigree of one extended family with symptoms suggestive of DSPS has been identified. Morningness-eveningness questionnaires were administered to all first- and second-degree relatives of a proband identified with DSPS. A total of 51 (86%) questionnaires were returned, and 6 adult biological relatives of 27 (22%) showed a preference for eveningness, which is much higher than reported in the general population. Both the paternal and maternal branches contained affected individuals, suggesting the possibility of a bilineal mode of inheritance. While the trait did not obey simple Mendelian inheritance, the vertical patterns of transmission were consistent with either an autosomal dominant mode of inheritance with incomplete penetrance or a multifactorial mode of inheritance. These data provide some preliminary support to the notion that eveningness, and thus DSPS, may have a genetic component. The prevalence of symptoms suggestive of DSPS is higher in this family than reported in the general population. Case reports such as this support the utility of larger, more systematic studies. It is unclear whether this degree of familiarity is representative of that in the general population.

The effects of exogenous melatonin on sleep, daytime sleepiness, fatigue, and alertness were investigated in 22 patients with delayed sleep phase syndrome whose nocturnal sleep was restricted to the interval from 24:00 to 08:00 hours. This study was a randomized, double-blind, placebo-controlled crossover trial. Subjects received either placebo or melatonin (5 mg) daily for 4 weeks, underwent a 1-week washout period, and then were given the other treatment for an additional 4 weeks. Patients could take the melatonin between 19:00 and 21:00 hours, which allowed them to select the time they felt to be most beneficial for the phase-setting effects of the medication.Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 weeks of melatonin treatment, and after 4 weeks of placebo treatment.In the 20 patients who completed the study, sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time), but there was a significant decrease in total sleep time while patients were taking placebo. Melatonin did not result in altered scores on subjective measures of sleepiness, fatigue, and alertness, which were administered at different times of the day. After an imposed conventional sleep period (from 24:00 to 08:00), subjects taking melatonin reported being less sleepy and fatigued than they did while taking placebo.Melatonin ameliorated some symptoms of delayed sleep phase syndrome, as confirmed by both objective and subjective measures. No adverse effects of melatonin were noted during the 4-week treatment period.

Circadian rhythm sleep disorders are poorly understood and often misdiagnosed. They are all related to the timing of sleep within the 24-hour day. This paper describes a patient with a long history of sleep disturbance whom we diagnosed as having delayed sleep phase syndrome by history and measurement of urinary melatonin metabolite excretion. Literature on the characteristics, diagnosis and management of this syndrome are briefly reviewed. In addition, the relation of the neurohormone melatonin to circadian rhythm and its other physiological roles are described.

Changes in the phase relation between sleep timing and the circadian pacemaker are suspected to have an etiological significance in circadian rhythm sleep disorders. Simultaneous recordings of rest-activity and rectal temperature in seven sighted delayed sleep phase syndrome (DSPS) patients, seven sighted non-24-h sleep-wake syndrome (non-24) patients, and 14 healthy controls were made for 10-14 days continuously in the subjects' homes. We found that sleep length and the interval from the body temperature (BT) trough to sleep offset were significantly longer in both non-24 and DSPS patients than in the controls, and that the interval between sleep onset and the BT trough was significantly less in the non-24 patients than in the DSPS patients and the controls. We postulate these alterations in phase relation to be associated with phase changes of the circadian pacemaker via different illumination timings.

The delayed sleep phase syndrome is characterized by an abnormally late sleeping and arousal time. Among several available treatments, chronotherapy, light therapy and melatonin administration strongly suggest a frequently recurring disturbance of the brain's circadian clock. However, several studies show psychological disturbances, which are either potentially a consequence or a cause or only fortuitously associated. The first case of disappearance of the disturbance after a move to a tropical latitude does not determine the main responsible factor.

Objective Delayed sleep phase syndrome (DSPS) is a condition in which the patient is unable to reset or phase-advance his/her sleep timing properly after transient sleep delay and consequently shows persistent sleep phase delay. Prior studies suggested that DSPS is associated with a phase delay in the circadian pacemaker, but there was no evidence to explain the patient's inability to reset sleep phase. Subjects and methods We used an ultra-short sleep-wake schedule together with simultaneous measurement of dim light melatonin rhythm after 24-hour sleep deprivation to allow the differential observation of diurnal sleep propensity fluctuation both from circadian and homeostatic aspects in 11 patients with DSPS (17-37 years; 8 men, 3 women) and 15 healthy controls (19-32 years; 8 men, 7 women). Setting NA. Patients or participants NA. Interventions NA. Results DSPS patients showed less ability to compensate for previous sleep loss during their circadian day and first hours of their circadian nighttime determined by dim light melatonin onset compared with controls, while controls compensated for previous sleep loss at most circadian times. Though shapes of dim light melatonin rhythm did not differ between the groups, phase angle between melatonin and sleep propensity rhythms was wider in DSPS patients than in controls. Conclusions These findings suggest that poor compensatory function for sleep loss predisposes DSPS patients to failure to reset their sleep phase. Our results provide implications for understanding not only the pathophysiology of DSPS but also the biological basis for why some people can change their sleep schedule easily according to personal or social demands while others cannot.

In addition to potentially providing insights into the molecular/biochemical basis of the restorative process, parallel studies of rest in Drosophila and sleep in mammals may provide candidate genes to assess in population genetic studies of sleep disorders and even in normal sleep (Figure 1Figure 1). A genetic basis is suspected for a number of human sleep disorders including both advanced sleep phase (Jones et al. 1999xJones, C.R., Campbell, S.S., Zone, S.E., Cooper, F., DeSano, A., Murphy, P.J., Jones, B., Czajkowski, L., and Ptacek, L.J. Nat. Med. 1999; 5: 1062–1065Crossref | PubMed | Scopus (335)See all ReferencesJones et al. 1999) and delayed sleep phase (Fink and Ancoli-Israel 1997xFink, R. and Ancoli-Israel, S. Sleep Res. 1997; 26: 713See all ReferencesFink and Ancoli-Israel 1997) syndromes, restless legs syndrome (Lazzarini et al. 1999xLazzarini, A., Walters, A.S., Hickey, K., Coccagna, G., Lugaresi, E., Ehrenberg, B.L., Picchietti, D.L., Brin, M.F., Stenroos, E.S., Verrico, T., and Johnson, W.G. Mov. Disord. 1999; 14: 111–116Crossref | PubMed | Scopus (84)See all ReferencesLazzarini et al. 1999), and narcolepsy (Mignot 1998xMignot, E. Neurology. 1998; 50: S16–S22Crossref | PubMedSee all ReferencesMignot 1998). Identification of the autosomal recessive mutation in canine narcolepsy as a defect in the hypocretin receptor 2 gene (Lin et al. 1999xLin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P.J., Nishino, S., and Mignot, E. Cell. 1999; 98: 365–376Abstract | Full Text | Full Text PDF | PubMed | Scopus (1696)See all ReferencesLin et al. 1999) and the narcoleptic-like phenotype of mice with a null mutation in the ligand for this receptor (Chemelli et al. 1999xChemelli, R.M., Willie, J.T., Sinton, C.M., Elmquist, J.K., Scammell, T., Lee, C., Richardson, J.A., Williams, S.C., Xiong, Y., Kisanuki, Y. et al. Cell. 1999; 98: 437–451Abstract | Full Text | Full Text PDF | PubMed | Scopus (1960)See all ReferencesChemelli et al. 1999) has encouraged researchers that understanding the genetic basis for human sleep disorders may be tractable.As in animal studies, certain aspects of normal sleep and the EEG appear to be highly heritable. Twin studies have demonstrated a genetic component in the occurrence of stages 2 and 4 and delta sleep, but not REM sleep (Linkowski 1999xLinkowski, P. J. Sleep Res. Suppl. 1999; 8: 11–13Crossref | PubMed | Scopus (74)See all ReferencesLinkowski 1999). A linkage marker for low-voltage alpha EEG has been identified on human chromosome 20q (Steinlein et al. 1992xSteinlein, O., Anokhin, A., Yping, M., Schalt, E., and Vogel, F. Genomics. 1992; 12: 69–73Crossref | PubMed | Scopus (80)See all ReferencesSteinlein et al. 1992). A study of 213 twin pairs determined the averaged heritabilites for the delta, theta, alpha, and beta frequencies of the EEG to be 76%, 89%, 89%, and 86%, respectively, indicating that brain electrical activity is one of the most heritable characteristics in humans (van Beijsterveldt et al. 1996xvan Beijsterveldt, C.E., Molenaar, P.C., de Geus, E.J., and Boomsma, D.I. Am. J. Hum. Genet. 1996; 58: 562–573PubMedSee all Referencesvan Beijsterveldt et al. 1996). Whether there is a genetic component to the propensity for habitually long (>9 hr) versus short (

Objectives The aim of this study was to find out how the occurrence of subjective daytime sleepiness (SDS) in schoolchildren had changed after 2 years follow-up and which were the predictors associated with persistence and appearance of SDS. Methods A total of 107 schoolchildren with SDS (Group 1) and an equal number without SDS (Group 2) were chosen to take part in the questionnaire study (age range 12-20 years). The questions concerned sleeping habits, sleep disorders and daytime sleepiness of the child and the family, progress at school and TV/video watching of the child, and social background of the family. A bivariate method (Pearson's chi-square) was used as a statistical tool. Results We received 68 replies (64%) from Group 1 and 75 (70%) from Group 2. Fifty-four schoolchildren were still sleepy in Group 1 and 28% had become sleepy in Group 2. The persistence of SDS in Group 1 was related to older age, irregular sleeping habits, frequent night waking and the fathers' sleep difficulties. The appearance of SDS in Group 2 was related to a high average grade at school. Conclusion A delayed sleep phase rhythm and problems staying asleep are obvious causes of persistent SDS, but the stress of schoolwork can also cause daytime sleepiness in schoolchildren.

Compared health-related quality of life of 43 delayed sleep phase syndrome (DSPS) patients (mean age 34.1 yrs) with a random Dutch sample of 1,063 Ss (aged 18-89 yrs) and 95 sleep apnea, 262 clinical depression, 546 migraine, and 194 osteoarthritis patients. The effectiveness of treatment with 5 mg of melatonin on the quality of life of DSPS patients was also investigated. DSPS patients completed a quality-of-life questionnaire (Medical Outcome Study Short Form-36 [MOS SF-36] health survey) just before and 2-9 mos after participation in a clinical trial involving the administration of melatonin. Scores were compared with responses to the same survey by a random Dutch sample and by the patients with sleep apnea, clinical depression, migraine, and osteoarthritis. MOS SF-36 scales scores were significantly lower in DSPS patients relative to age- and gender-adjusted norms for the Dutch sample. Some health dimensions were more affected, and others less affected, by DSPS compared with the other chronic conditions. Melatonin treatment improved all scales except the scale "role due to emotional problems." It is concluded that DSPS has a unique significant quality-of-life burden that seems to be improved by treatment with melatonin. (PsycINFO Database Record (c) 2000 APA, all rights reserved)

JR is an 18-year-old male with five-year history of going to bed late and waking up late. He gives history of poor frustration tolerance, inattention and fidgetiness in school for which he has been unsuccessfully been treated with stimulant medications for last 3 years. There is history of similar sleep problems in his father who works nights as a mechanic. JR's sleep log shows him going to bed early morning and waking up late morning/afternoon. He shows no sleep maintenance problems and sleeps an average of 8 h per night. He shows no symptoms of depression, anxiety, inattention or hyperactivity during his hospital stay. He does not show any learning, cognitive, attention or intellectual deficits. He is currently not taking any medications. He is discharged home after 3-day hospital stay and is reportedly doing well working in a video rental store at night.

These clinical guidelines were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the use of light therapy for treatment of various sleep disorders. This paper is based on a series of articles in the Journal of Biological Rhythms and also includes evidence tables from an updated Medline review covering the period January 1994 to December 1997. Evidence is presented by grade and level. Recommendations are identified as standards, guidelines, or options. Recommendations are provided for delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), non-24-hour sleep-wake syndrome, jet lag, shift work, dementia, and sleep complaints in the healthy elderly. Light therapy appears generally safe if used within recommended intensity and time limits. Light therapy can be useful in treatment of DSPS and ASPS. Benefits of light therapy are less clear and treatment is an option in jet lag, shift work, and non-24-hour sleep-wake syndrome in some blind patients.

The pineal product melatonin is involved in the regulation of the sleep/wake cycle in humans. In blind individuals and in people travelling through time zones, melatonin rhythms are sometimes unsynchronized with the diel cycle, and nocturnal sleep may be disturbed. Low or distorted melatonin rhythms have repeatedly been reported in middle aged and elderly insomniacs. Melatonin administration effectively synchronized the sleep wake cycle in blind individuals and in subjects suffering from jet lag and advanced sleep onset in subjects suffering from delayed sleep phase syndrome. In elderly insomniacs, melatonin replacement therapy significantly decreased sleep latency, and/or increased sleep efficiency and decreased wake time after sleep onset. In addition, melatonin substitution facilitated benzodiazepine discontinuation in chronic users. These data show an association between melatonin rhythm disturbances and difficulties to promote or maintain sleep at night. Specific melatonin formulations may be useful to treat circadian-rhythm-related sleep disorders and age-related insomnia.