Sleep and the Social Profiles of Individuals With Rett Syndrome.

BACKGROUND: This study investigates the distinctive social behaviors observed in individuals with Rett syndrome (RTT), characterized by the loss of spoken language, impaired eye gaze communication, gait abnormalities, and sleep issues. The research aims to identify social profiles in RTT and explore their correlation with sleep, sleep-disordered breathing (SDB), and daytime sleepiness. METHODS: Standard overnight sleep macrostructure and respiratory parameters were assessed. Extracting 25 social-related items and one for daytime sleepiness from the Rett Syndrome Behavioral Questionnaire, factor analysis was applied to establish latent social profiles. These profiles were then correlated with sleep parameters. The nonparametric Mann-Whitney U test compared social profiles based on the presence of SDB (defined by an apnea-hypopnea index greater than one per hour) and daytime sleepiness. RESULTS: The study involved 12 female subjects with confirmed RTT diagnoses and MECP2 mutations, aged 8.54 ± 5.30 years. The Rett Syndrome Behavioral Questionnaire revealed a total average score of 25.83 ± 12.34, indicating varying degrees of social impairments. Comprising 25 social-related items, factor analysis yielded four social profiles: "interactive motricity," "mood change," "anxiety/agitation," and "gazing." Longer sleep onset latency correlated with increased socio-behavioral impairments, particularly in interactive motricity reduction. Conversely, higher rapid eye movement sleep was associated with fewer interactive socio-motor behaviors. No significant differences in social profiles were found concerning the presence of SDB or daytime sleepiness. CONCLUSIONS: The findings suggest four distinct social profiles in RTT individuals, hinting at shared disrupted circuits between sensorimotor functioning and sleep-related neuronal pathways. Despite the absence of differences in SDB or daytime sleepiness, the study highlights the relationship between sleep parameters, such as sleep onset latency and rapid eye movement sleep, and socio-behavioral outcomes in RTT with MECP2 mutations.

Domestication of the Dromedary Revisited and Its Consequences for Legislation as to Keeping Livestock or Pet Animals.

Being in an advanced stage of domestication is a newly proposed requirement to decide which animals can be safely kept by humans. Dutch legislators were the first to apply it and other European countries may be tempted to adopt a similar approach. Unexpectedly, the Dutch assessors considered the dromedary (Camelus dromedarius) as being insufficiently domesticated and this species will therefore no longer be able to be kept as a production animal from 2024 onwards. In a recent publication on this topic, we showed that the domestication of the dromedary is actually very advanced. In this paper, we apply the same criteria that were used by the Dutch assessors to determine the degree of domestication, taking into account the most recent scientific developments in this area, even though it should be noted that these criteria have neither been peer-reviewed, nor published in an international scientific journal. For the sake of comparison, and in order to validate the procedure, we also applied these criteria to the house cat. The results confirm that the dromedary is highly domesticated, but also that the house cat (Felis silvestris catus) is at most semi-domesticated. Obviously, we agree with the decision of the Dutch legislators to place the house cat on the positive list, but our analysis demonstrates that this was decided on false grounds. Our analysis makes it clear that the requirement of being in an advanced stage of domestication is not suitable. Instead of maintaining this requirement, we recommend implementing evidence-based, peer-reviewed methods to decide which animals can be kept by humans, and to include species specific-guidelines in the legislation on how this can be achieved safely.

An investigation of the sleep macrostructure of girls with Rett syndrome.

OBJECTIVE/BACKGROUND: Methyl-CpG-binding protein 2 (MeCP2) is of utmost importance in neuronal function. We aim to characterize phenotypic traits in the sleep of individuals with Rett Syndrome (RTT, OMIM # 312750), a rare disorder predominantly caused by mutations of the MECP2 gene. PATIENTS/METHODS: An overnight polysomnographic recording was performed. Outcomes investigated were parameters of nocturnal sleep macrostructure, and sample stratification per genetic and clinical characteristics, and six key features of clinical severity was applied. RESULTS: The sleep of our 21 RTT female subjects with a mutant MECP2 gene, aged 8.8 ± 5.4 years, showed no significant differences within strata. However, compared to a normative dataset, we found longer duration of wake time after sleep onset and total sleep time (TST) but shorter sleep onset latency, in RTT. Regarding the proportion of sleep stages per TST, higher stage N3 (%) with lower stage N2 (%) and REM (%) were generally seen. Such abnormalities became more uniformly expressed at the severe level of clinical features, particularly for hand functioning and walking. CONCLUSIONS: RTT girls with MECP2 mutations in our study demonstrated an increased deep sleep and reduced rapid eye movement sleep proportion, which is mostly allied with their hand dysfunction severity. Poor sleep-on/off switching in RTT since embryogenesis is possibly linked to (psycho)motor impairment in the cases with MECP2 mutations.

Off-label low dose amitriptyline for insomnia disorder: Patient-reported outcomes.

PURPOSE: Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient-reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data. METHODS: Cross-sectional study: Seven hundred fifty-two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10-20 mg based on self-titration). Treatment was intended to improve sleep maintenance. Before the planned follow-up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple-choice questions with room for free-text elaboration. RESULTS: 53.7% of the patients reported to use amitriptyline up to 10 mg/day, 42.9% used a self-increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline. CONCLUSION: These patient-reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term.

Sleep Respiratory Disturbances in Girls with Rett Syndrome.

Individuals with Rett Syndrome (RTT), a rare neurodevelopmental disorder, present disordered breathing during wakefulness. Whilst findings on breathing during sleep are contradictory, the relation between sleep breathing and their clinical features, genetic characteristics, age, and sleep phase is rarely investigated, which is the objective of this study. Overnight polysomnography (PSG) was performed. Sleep macrostructure parameters were compared between the RTT subjects with and without sleep-disordered breathing (SDB). The association between the apnea-hypopnea index (AHI) with age at PSG was tested. Particularly for RTT subjects with SDB, the respiratory indexes in REM and NREM sleep were compared. Stratified analyses per clinical characteristics, genetic characteristics, and clinical features' severity were performed. Non-parametric statistics were applied. A sample of 11 female RTT subjects, aged 8.69 ± 5.29 years with ten confirmed with MECP2 mutations, were studied. The average AHI was 3.94 ± 1.19/h TST, of which eight (72.73%) had obstructive sleep apnea, i.e., six in 1/h TST ≤ AHI ≤ 5/h TST, and two in AHI > 5/h TST. The mean SpO2% was 81.00 ± 35.15%. The AHI was not significantly correlated with their age at PSG (rs = -0.15, p = 0.67). Sleep macrostructure in SDB-absent and SDB-present groups was not different. Respiratory indexes in those with obstructive sleep apnea showed no difference between REM and NREM sleep nor any of the strata. In our clinical sample, more than half of the RTT subjects with MECP2 mutations had obstructive sleep apnea in both NREM and REM sleep which was unrelated to their clinical features. Our results also indicated hypoxemia throughout nocturnal sleep in RTT. To conclude, our results suggest that disordered breathing during sleep is prevalently present in RTT as an independent clinical feature.

The Flourishing Camel Milk Market and Concerns about Animal Welfare and Legislation.

The worldwide dromedary milk production has increased sharply since the beginning of this century due to prolonged shelf life, improved food-safety and perceived health benefits. Scientific confirmation of health claims will expand the market of dromedary milk further. As a result, more and more dromedaries will be bred for one purpose only: the highest possible milk production. However, intensive dromedary farming systems have consequences for animal welfare and may lead to genetic changes. Tighter regulations will be implemented to restrict commercialization of raw milk. Protocols controlling welfare of dromedaries and gene databases of milk-dromedaries will prevent negative consequences of intensive farming. In countries where dromedaries have only recently been introduced as production animal, legislators have limited expertise on this species. This is exemplified by an assessment on behalf of the Dutch government, recommending prohibiting keeping this species from 2024 onwards because the dromedary was deemed to be insufficiently domesticated. Implementation of this recommendation in Dutch law would have devastating effects on existing dromedary farms and could also pave the way for adopting similar measures in other European countries. In this paper it is shown that the Dutch assessment lacks scientific rigor. Awareness of breeders and legislators for the increasing knowledge about dromedaries and their products would strengthen the position of dromedaries as one of the most adapted and sustainable animals.

Chrono-Nutrition and Diet Quality in Adolescents with Delayed Sleep-Wake Phase Disorder.

Background: Delayed sleep-wake phase disorder (DSPD), characterized by delayed sleep-onset and problems with awakening in the morning, is mostly prevalent in adolescents. Several studies have suggested chrono-nutrition could present a possible modifiable risk factor for DSPD. Objective: To describe differences in chrono-nutrition and diet quality in adolescents with DSPD compared to age-related controls. Methods: Chrono-nutrition and diet quality of 46 adolescents with DSPD, aged 13-20 years, and 43 controls were assessed via questionnaires. Diet quality included the Dutch Healthy Diet index (DHD-index) and Eating Choices Index (ECI). Results were analysed using logistic regression and Spearman's partial correlation. Results: Compared with controls, DSPD patients consumed their first food of the day significantly later on weekdays (+32 ± 12 min, p = 0.010) and weekends (+25 ± 8 min, p = 0.005). They consumed their dinner more regularly (80.4% vs. 48.8%, p = 0.002) and consumed morning-snacks less frequently (3.0 ± 2.1 days vs. 4.2 ± 1.7 days, p = 0.006). No differences in clock times of breakfast, lunch, or dinner were found. Moreover, no significant differences in overall diet quality were observed. Conclusion: This descriptive study showed chrono-nutritional differences between adolescents with and without DPSD. Further studies are needed to explore features of chrono-nutrition as a possible treatment of DPSD.

Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of melatonin in the treatment of sleep onset insomnia in children and adolescents. METHODS: Electronic databases and bibliographies of relevant reports were searched for randomized, placebo-controlled, clinical trials that used melatonin in children and adolescents with sleep onset insomnia. The quality of the included studies was assessed by the Cochrane Collaboration's risk-of-bias method. The mean differences (MD) and the odds ratios (OR) with 95% confidence interval (CI) were estimated by a random-effects model. Primary outcomes were sleep onset time (SOT), drop-out for all causes and drop-out for adverse events. Secondary outcomes included dim light melatonin onset (DLMO), sleep onset latency (SOL), total sleep time (TST), light-off time, and wake-up time. RESULTS: Seven trials with 387 participants were finally included after a systematic search. The overall quality of the included studies was low to moderate. SOT in patients receiving melatonin advanced more than patients receiving placebo (MD = -0.62 h, 95% CI -0.80, -0.45), as well as DLMO (MD = -0.82 h, 95% CI -1.23, -0.41). No differences were found in the outcome of drop-out for all causes (OR = 1.51, 95% CI 0.57, 4.05) or drop-out for adverse events (OR = 3.35, 95% CI 0.13, 86.03). Severe adverse events, migraine, and mild generalized epilepsy were reported in two cases. SOL decreased and TST increased, MD = -0.36 h (95% CI -0.49, -0.24) and MD = 0.38 h (95% CI 0.09, 0.66), respectively. Light-off time and wake-up time did not differ significantly. CONCLUSIONS: Melatonin was an effective and tolerable drug in the short-term treatment of sleep onset insomnia in children and adolescents. More studies, especially in adolescents, are needed to investigate the efficacy and safety of melatonin.

Efficacy and safety of supplemental melatonin for delayed sleep-wake phase disorder in children: an overview.

Delayed sleep-wake phase disorder (DSPD) is the most frequently occurring intrinsic circadian rhythm sleep-wake disorder, with the highest prevalence in adolescence. Melatonin is the first-choice drug treatment. However, to date melatonin (in a controlled-release formulation) is only authorised for the treatment of insomnia in children with autism or Smiths-Magenis syndrome. Concerns have been raised with respect to the safety and efficacy of melatonin for more general use in children, as melatonin has not undergone the formal safety testing required for a new drug, especially long-term safety in children. Melatonin is known to have profound effects on the reproductive systems of rodents, sheep and primates, as well as effects on the cardiovascular, immune and metabolic systems. The objective of the present article was therefore to establish the efficacy and safety of exogenous melatonin for use in children with DSPD, based on in vitro, animal model and clinical studies by reviewing the relevant literature in the Medline database using PubMed. Acute toxicity studies in rats and mice showed toxic effects only at extremely high melatonin doses (>400 mg/kg), some tens of thousands of times more than the recommended dose of 3-6 mg in a person weighing 70 kg. Longer-term administration of melatonin improved the general health and survival of ageing rats or mice. A full range of in vitro/in vivo genotoxicity tests consistently found no evidence that melatonin is genotoxic. Similarly long term administration of melatonin in rats or mice did not have carcinogenic effects, or negative effects on cardiovascular, endocrine and reproductive systems. With regard to clinical studies, in 19 randomised controlled trials comprising 841 children and adolescents with DSPD, melatonin treatment (usually of 4 weeks duration) consistently improved sleep latency by 22-60 min, without any serious adverse effects. Similarly, 17 randomised controlled trials, comprising 1374 children and adolescents, supplementing melatonin for indications other than DSPD, reported no relevant adverse effects. In addition, 4 long-term safety studies (1.0-10.8 yr) supplementing exogenous melatonin found no substantial deviation of the development of children with respect to sleep quality, puberty development and mental health scores. Finally, post-marketing data for an immediate-release melatonin formulation (Bio-melatonin), used in the UK since 2008 as an unlicensed medicine for sleep disturbance in children, recorded no adverse events to date on sales of approximately 600,000 packs, equivalent to some 35 million individual 3 mg tablet doses (MHRA yellow card adverse event recording scheme). In conclusion, evidence has been provided that melatonin is an efficacious and safe chronobiotic drug for the treatment of DSPD in children, provided that it is administered at the correct time (3-5 h before endogenous melatonin starts to rise in dim light (DLMO)), and in the correct (minimal effective) dose. As the status of circadian rhythmicity may change during long-time treatment, it is recommended to stop melatonin treatment at least once a year (preferably during the summer holidays).

Long-Term Melatonin Therapy for Adolescents and Young Adults with Chronic Sleep Onset Insomnia and Late Melatonin Onset: Evaluation of Sleep Quality, Chronotype, and Lifestyle Factors Compared to Age-Related Randomly Selected Population Cohorts.

The extent of continuance of melatonin therapy initiated in pre-pubertal children with chronic sleep onset insomnia (CSOI) was investigated in young adult life. Sleep timing, sleep quality, adverse events, reasons for cessation of therapy, and patient characteristics with regard to therapy regimen, chronotype and lifestyle factors possibly influencing sleeping behavior were assessed. With an online survey using questionnaires (Pittsburgh Sleep Quality Index, Insomnia Severity Index, Morningness-Eveningness Questionnaire, and Munich Chronotype Questionnaire), outcomes were measured and compared with age-related controls. These controls were extracted from published epidemiological research programs applying the same questionnaires. At the moment of the survey, melatonin was still continued by 27.3% of the patients, with a mean treatment duration of 10.8 years. The overall average treatment duration was 7.1 years. Sleep quality of both discontinued and persistent melatonin users did not deviate from controls. Sleep timing and chronotype scores indicated evening type preference in all responders. Adverse events were scarce but the perceived timing of pubertal development suggested a tendency towards delayed puberty in former and current users of melatonin. This study may underestimate the number of children that are able to stop using melatonin due to the response rate (47.8%) and appeal for continuing users. Sleep timing parameters were based on self-reported estimates. Control populations were predominantly students and were of varying nationalities. The statistical power of this study is low due to the limited sample size. Melatonin therapy sustained for 7.1 years does not result in substantial deviations of sleep quality as compared to controls and appears to be safe. The evening type preference suggests a causal relation with CSOI. This study shows that ten years after initiation of treatment with melatonin for CSOI, approximately 75% of the patients will have normal sleep quality without medication.

Low maternal melatonin level increases autism spectrum disorder risk in children.

BACKGROUND: It is assumed that autism spectrum disorder (ASD) is caused by a combination of de novo inherited variation and common variation as well as environmental factors. It often co-occurs with intellectual disability (ID). Almost eight hundred potential causative genetic variations have been found in ASD patients. However, not one of them is responsible for more than 1% of ASD cases. Low melatonin levels are a frequent finding in ASD patients. Melatonin levels are negatively correlated with severity of autistic impairments, it is important for normal neurodevelopment and is highly effective in protecting DNA from oxidative damage. Melatonin deficiency could be a major factor, and well a common heritable variation, that increases the susceptibility to environmental risk factors for ASD. ASD is already present at birth. As the fetus does not produce melatonin, low maternal melatonin levels may be involved. METHODS: We measured 6-sulfatoxymelatonin in urine of 60 mothers of a child with ASD and controls. RESULTS: 6-sulfatoxymelatonin levels were significantly lower in mothers with an ASD child than in controls (p = 0.012). CONCLUSIONS: Low parental melatonin levels could be one of the contributors to ASD and possibly ID etiology. Our findings need to be duplicated on a larger scale. If our hypothesis is correct, this could lead to policies to detect future parents who are at risk and to treatment strategies to ASD and intellectual disability risk.

Chronic sleep reduction in adolescents-clinical cut-off scores for the Chronic Sleep Reduction Questionnaire (CSRQ).

The Chronic Sleep Reduction Questionnaire is a validated questionnaire that measures symptoms of prolonged insufficient and/or poor sleep and therefore accounts for individuals' sleep need and sleep debt. This study extends its psychometric properties by providing cut-off scores, using a matched sample of 298 healthy adolescents (15.38 ± 1.63 years, 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 32.98 ± 6.51) and 298 adolescents with insomnia/delayed sleep-wake phase disorder (15.48 ± 1.62 years; 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 42.59 ± 7.06). We found an area under the curve of 0.84 (95% confidence interval: 0.81-0.87). Cut-off scores for optimal sensitivity, optimal specificity and based on Youden's criterion are provided. These cut-off scores are highly relevant for use of the Chronic Sleep Reduction Questionnaire in future studies and clinical practice.

Effects of Melatonin and Bright Light Treatment in Childhood Chronic Sleep Onset Insomnia With Late Melatonin Onset: A Randomized Controlled Study.

Study Objectives: Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset. Methods: Eighty-four children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N = 26), light (N = 30), or placebo pills (N = 28) for 3 to 4 weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analyzed with linear mixed model analyses. Results: Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found. Conclusions: We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment.

Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study.

Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light.

Precision medicine in circadian rhythm sleep-wake disorders: current state and future perspectives.

In circadian rhythm sleep-wake disorders precision medicine is less developed than in other medical disciplines mainly because homeostatic sleep and circadian timing have a very complex phenotype with multiple genetic regulation mechanisms. However, biomarkers, phenotyping and psychosocial characteristics are increasingly used. Devices for polysomnography, actigraphy and sleep-tracking applications in mobile phones and other consumer devices with eHealth technologies are increasingly used. Also sleep-related questionnaires and the assessment of co-morbidities influencing sleep in circadian rhythm sleep-wake disorders are major contributors to precision sleep medicine. To further strengthen the (pharmaco-)genetic and biomarker pillar, technology needs to be evolved further. Routinely measuring treatment results using patient-reported outcome measures and clinical neurophysiological instruments will boost precision sleep medicine.

Sleep and Circadian Rhythmicity in Adult ADHD and the Effect of Stimulants.

OBJECTIVE: This review updates information on sleep and circadian rhythmicity in adult ADHD, especially circadian rhythmicity and the influence of stimulants. METHOD: Investigations into sleep, chronotype, and circadian rhythm in adult ADHD were searched in the Cochrane Library, Embase, Medline, and PsycInfo databases. RESULTS: ADHD in adults is associated with longer objective sleep latency, irrespective of insomnia complaints. Sleep maintenance is disturbed and waking up time is delayed. Adult ADHD is associated with increased eveningness, delayed dim light melatonin onset (DLMO), and later waking up time. Stimulant treatment induces delay of nonparametric circadian parameters, whereas light therapy (LT) induces shifts toward morningness, which is associated with a reduction of ADHD symptoms. CONCLUSION: Adult ADHD is associated with delayed circadian rhythmicity and analogous sleep characteristics, which are typical of a delayed sleep phase disorder. Stimulants induce delay of circadian rhythmicity.

Sleep Complaints and the 24-h Melatonin Level in Individuals with Smith-Magenis Syndrome: Assessment for Effective Intervention.

AIMS: Individuals with Smith-Magenis syndrome (SMS) are reported to have a disrupted circadian rhythm. Our aim was to examine problematic sleeping in those attending our sleep clinic for the first time. METHODS: At intake, caregivers of 50 children and nine adults with SMS were surveyed about the sleep pattern and potential melatonin administration. Sampling of salivary melatonin levels was performed. RESULTS: At intake, exogenous melatonin was used by 16 children (27.1% of sample; 56.3% male) with mean age 6.8 ± 2.8 years, whereas 34 children (57.6%; 7.5 ± 4.8 years old; 64.7% male) and nine adults (15.3%; 36.8 ± 15.3 years old; 44.4% male) were not taking melatonin at intake. Participants were reported to have problems with night waking and early awakenings regardless of melatonin administration. Overall, moderate to high levels of salivary melatonin at noon were found in individuals with SMS. In particular, children with SMS showed a disrupted melatonin pattern. Furthermore, the endogenous melatonin level, age, and gender may potentially interact, yielding the severity range of sleep disturbances reported in SMS. CONCLUSION: Treatment of sleep problems in SMS is complex, and our findings may support person-centered sleep and medication management. Future clinical trials including larger groups may shed light on such approaches.

Prevalence of Restless Legs Syndrome in Adult ADHD and Its Subtypes.

In this observational cross-sectional study, 49 subjects were assessed for sleep disorders and for ADHD symptoms. Thirty-six received an ADHD diagnosis (29: combined type (ADHD-C); 7: inattentive type). An RLS and RLS symptoms prevalence of 34.5% was found, with a higher prevalence rate in the ADHD-C subgroup, although not significantly (p = 0.066). RLS symptoms were correlated with particularly hyperactivity-impulsivity (ρ = 0.742; p: 0.000). ADHD patients with positive RLS scores reported higher scores on the ADHD-Rating scale compared with patients with negative RLS scores (Z: -2.968, p = 0.003), mainly due to higher hyperactivity-impulsivity scores (Z: -3.145; p = 0.002). Our findings show that clinicians need to be aware of RLS among adult ADHD patients, particularly those with severe hyperactivity-impulsivity symptoms.

Extreme Violation of Sleep Hygiene: Sleeping Against the Biological Clock During a Multiday Relay Event.

BACKGROUND: Sleep hygiene is important for sleep quality and optimal performance during the day. However, it is not always possible to follow sleep hygiene requirements. In multiday relay events, athletes have to sleep immediately after physical exertion and sometimes against their biological clock. OBJECTIVES: In this pilot study we investigated the effect of having to sleep at an abnormal circadian time on sleep duration. PATIENTS AND METHODS: Eight runners and two cyclists performing a 500 km relay race were followed. They were divided into two groups that took turns in running and resting. Each group ran four times for approximately five hours while the other group slept. As a result, sleep times varied between normal and abnormal times. All athletes wore actigraphs to record the duration and onset of sleep. RESULTS: Linear mixed model analyses showed that athletes slept on average 43 minutes longer when they slept during usual (night) times than during abnormal (day) times. In general, sleep duration decreased during the race with on average 18 minutes per period. CONCLUSIONS: This pilot study shows that, even under extreme violation of sleep hygiene rules, there still is an apparent effect of circadian rhythm on sleep duration in relay race athletes.