Delayed Sleep-wake Phase Disorder Research Articles

Low dose exogenous melatonin plus evening dim light and time in bed scheduling advances circadian phase irrespective of measured or estimated dim light melatonin onset time: preliminary findings.

The purpose of the present study was to preliminarily evaluate whether knowing the dim light melatonin onset (DLMO) time is advantageous when treating delayed sleep-wake phase disorder (DSWPD) with low dose melatonin treatment plus behavioral interventions (i.e., evening dim light and time in bed (TIB) scheduling). In this randomized, controlled, double-blind trial, 40 adults with DSWPD were randomly assigned to 4 weeks of 0.5 mg timed to be administered either 3 hours before the DLMO (measured DLMO group, n = 20) or 5 hours before sleep onset time per actigraphy (estimated DLMO group, n = 20), in conjunction with behavioral interventions. The primary outcome was change in the DLMO (measured in-home). Secondary outcomes included sleep parameters per diary and actigraphy (sleep onset and offset times and total sleep time), Morningness-Eveningness Questionnaire (MEQ), Multidimensional Fatigue Inventory (MFI), PROMIS-Sleep Disturbance (SD), PROMIS-Sleep Related Impairment (SRI), and Pittsburgh Sleep Quality Index (PSQI). Mixed effects models tested for group differences in these outcome. After applying the Bonferroni correction for multiple comparisons (significant p-value set at ˂ .004), there were significant main effects for visit on all outcomes except PSQI and total sleep time per wrist actigraphy and diary. There were no group by visit interactions for any of the outcomes (p > .004). Scheduled low dose melatonin plus behavioral interventions may improve many circadian and sleep parameters regardless of whether melatonin administration is scheduled based on estimated or measured DLMO. A larger-scale trial is needed to confirm these preliminary findings. Clinicaltrials.gov Identifier: NCT03715465; Name: The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder; URL: https://clinicaltrials.gov/study/NCT03715465.

Dim Light Melatonin Onset analysis in individuals diagnosed with Delayed Sleep-Wake Phase Disorder (DSWPD)

Dim Light Melatonin Onset analysis in individuals diagnosed with Delayed Sleep-Wake Phase Disorder (DSWPD)

Enrichment of melanopsin genetic variants in a Delayed Sleep-Wake Phase Disorder (DSWPD) patient – whole genome sequencing analysis

Enrichment of melanopsin genetic variants in a Delayed Sleep-Wake Phase Disorder (DSWPD) patient – whole genome sequencing analysis

Is the treatment worth the effort? Light therapy, melatonin and sleep scheduling for Delayed Sleep-Wake Phase Disorder (DSWPD): a qualitative study

Is the treatment worth the effort? Light therapy, melatonin and sleep scheduling for Delayed Sleep-Wake Phase Disorder (DSWPD): a qualitative study

The optimal dose of Ramelteon for the better treatment adherence of delayed sleep-wake phase disorder: a dropout rate study.

Evidence regarding the effectiveness of melatonin receptor agonists in treating delayed sleep-wake phase disorder (DSWPD) remains limited. This study aimed to determine the optimal dose of ramelteon, a melatonin receptor agonist, for the better treatment adherence of DSWPD. The patients who were diagnosed definitely as having DSWPD by board-certified physicians specialized in sleep medicine and started to receive strategically timed ramelteon medications after the diagnosis were included. Data on the initial ramelteon dose and follow-up duration (up to 24 months) were collected retrospectively. Patients with treatment discontinuation, changes in ramelteon dose, or the addition of other sleep-related medications were considered dropouts. Kaplan-Meier estimates, log-rank tests, and Cox regression analyses were performed. Overall, 373 patients were analyzed. The findings revealed that the 2 mg dose of ramelteon was associated with a lower dropout rate compared to the other doses (8 mg, 4 mg, and 1 mg). The dropout rate for the 2 mg group was estimated to have a hazard ratio (HR) of 0.5762 when compared with the 8 mg dose group. Sex did not reveal a significant HR, whereas older age exhibited a small but significant HR (0.9858). For achieving better adherence, a dosing regimen of strategically timed 2 mg ramelteon may be the best for the treatment of DSWPD. The therapeutic dose window for better adherence seems to center approximately 2 mg of ramelteon. Furthermore, caution should be exercised when treating younger patients to prevent dropouts.

Effects of exogenous melatonin on sleep and circadian rhythm parameters in bipolar disorder with comorbid delayed sleep-wake phase disorder: An actigraphic study

The present study evaluates the effect of exogenous melatonin (exo-MEL) on sleep and circadian parameters in patients with bipolar disorder (BD) and delayed sleep-wake phase disorder (DSWPD). BD euthymic patients (n = 83, mean age = 45.13 ± 13.68, males 56%) were evaluated for chronotype (reduced Morningness-Eveningness Questionnaire [rMEQ]), sleep quality (Pittsburgh Sleep Quality Index), sleep and circadian parameters (actigraphic monitoring). Patients that fulfilled criteria for DSWPD (n = 25) were treated for three months with exo-MEL 2 mg administered approximately 4 h before the sleep onset time (SOT) actigraphically-determined at baseline. Sleep and circadian parameters at baseline (T0) and after the exo-MEL treatment (T1) were compared using paired Wilcoxon test. In patients that completed the treatment (n = 19), the rMEQ score increased between T0 (median = 8.0 [IQR = 7.0, 11.0]) and T1 (median = 13.5 [IQR = 9.3, 15.0], p-value = 0.006), the SOT was advanced between T0 (median = 00:55 [IQR = 00:25, 01:39] and T1 (median = 00:09 [IQR = 23:41, 01:04], p-value = 0.039), the sleep efficiency and total sleep time increased (T0: median = 84.4 [IQR = 81.3, 89.4]; T1 (median = 90.3 [IQR = 85.5, 92.9] %, p-value = 0.01, and T0: median = 7.20 [IQR = 6.15, 8.15]; T1: median = 7.7 [IQR = 7.0, 9.3] hours, p-value = 0.04, respectively). These results indicate that in BD with comorbid DSWPD, the self-reported chronotype, the sleep onset time, and sleep efficiency and duration were modified after a personalized treatment with exo-MEL, suggesting its potential efficacy in improving sleep patterns in BD. The absence of proper control groups and of treatment randomization constitute limitations of our study and further randomized controlled trials are required to confirm our results.

0035 Melanopsin genetic variants and delayed sleep phenotype – whole genome sequencing analysis

Abstract Introduction Melanopsin (OPN4) is a blue light-sensitive opsin-type G-protein coupled receptor. It is highly expressed in photosensitive retinal ganglion cells which mediate responses to light, including regulation of sleep, circadian photoentrainment, and pupillary light response. Mutations in OPN4 were shown to affect responses to light, ultimately affecting the regulation of circadian rhythms and sleep. Previously, we describe a male carrier of the OPN4 missense variant diagnosed with delayed sleep-wake phase disorder (DSWPD), with a consistent recurrent pattern of delayed sleep onset The rs143641898 [NM_033282.4:c.502C>T p.(Arg168Cys)] variant in the OPN4 gene that was shown in a functional study to render the OPN4 protein non-functional. Methods The analysis was conducted on whole genome sequencing samples obtained from patients with a clinical diagnosis of DSWPD. Age and sex-matched samples were used as controls. Results Here we report an enrichment of OPN4 rare coding variants, MAF< 1, in a set of 117 DSWPD samples as compared to 315 healthy controls. This significant enrichment likely implies that other rare pLOFs can similarly contribute to the delayed sleep phenotype. Moreover, we report a significant association of rs rs1079610, a common variant in OPN4 – with delayed bedtime in DSWPD patients. This variant has been previously reported in association with altered pupillary responses. This effect is not seen in a large set of healthy controls without DSWPD diagnosis. Conclusion The OPN4 discussed rare OPN4 variants likely increase the risk of DSWPD via its direct effect on the pathophysiology along the melanopsin axis. This study offers useful insights for the differential diagnosis and ultimately treatment of DSWPD risk in which patients carry pathogenic variants in the OPN4 gene. Support (if any)

Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.

Delayed sleep-wake phase disorder (DSWPD) is a sleep disorder in which the habitual sleep-wake timing is delayed, resulting in difficulty in falling asleep and waking up at the desired time. Patients with DSWPD frequently experience fatigue, impaired concentration, sleep deprivation during weekdays, and problems of absenteeism, which may be further complicated by depressive symptoms. DSWPD is typically prevalent during adolescence and young adulthood. Although there are no studies comparing internationally, the prevalence of DSWPD is estimated to be approximately 3% with little racial differences between Caucasians and Asians. The presence of this disorder is associated with various physiological, genetic and psychological as well as behavioral factors. Furthermore, social factors are also involved in the mechanism of DSWPD. Recently, delayed sleep phase and prolonged sleep duration in the young generation have been reported during the period of COVID-19 pandemic-related behavioral restrictions. This phenomenon raises a concern about the risk of a mismatch between their sleep-wake phase and social life that may lead to the development of DSWPD after the removal of these restrictions. Although the typical feature of DSWPD is a delay in circadian rhythms, individuals with DSWPD without having misalignment of objectively measured circadian rhythm markers account for approximately 40% of the cases, wherein the psychological and behavioral characteristics of young people, such as truancy and academic or social troubles, are largely involved in the mechanism of this disorder. Recent studies have shown that DSWPD is frequently comorbid with psychiatric disorders, particularly mood and neurodevelopmental disorders, both of which have a bidirectional association with the pathophysiology of DSWPD. Additionally, patients with DSWPD have a strong tendency toward neuroticism and anxiety, which may result in the aggravation of insomnia symptoms. Therefore, future studies should address the effectiveness of cognitive-behavioral approaches in addition to chronobiological approaches in the treatment of DSWPD.

The impact of daylight-saving time (DST) on patients with delayed sleep-wake phase disorder (DSWPD).

Due to time zones, sun time and local time rarely match. The difference between local and sun time, which we designate by Solar Jet Lag (SoJL), depends on location within a time zone and can range from zero to several hours. Daylight saving time (DST) simply adds 1 h to SoJL, independently of the location. We hypothesised that the impact of DST is particularly problematic in patients with delayed sleep-wake phase disorder (DSWPD), worsening their sleep debt. DSWPD is characterised by a chronic misalignment between the internal and social timing, reflected by an inability to fall asleep and wake-up at conventional or socially acceptable times. We analysed the clinical records of 162 DSWPD patients from a sleep medicine centre in Lisbon, Portugal (GMTzone), and separated them into two groups: the ones diagnosed across DST or across Standard Time (ST). We included 82 patients (54.9% male; age: median [Q1 , Q3 ] 34.5 [25.0, 45.3]; range 16-92; 54 in DST and 28 in ST) who had Dim Light Melatonin Onset (DLMO) measured as a marker for the circadian phase and sleep timing (onset, SO, mid-point, MS and end, SE) self-reported separately for work- and work-free days. Differences between ST and DST were compared using Mann-Whitney or Student's t-tests. On a weekly average, patients in DST slept less (difference between medians of 37 min. p < .01), mainly due to sleep on workdays (SDw, p < .01), which also correlated with SoJL (rsp = .38, p < .01). While the time from DLMO to SO was similar in those in ST or those in DST, the time from DLMO to SE was significantly shorter for those in DST. The average duration between DLMO and sleep end was close to 10.5 h in ST, the biological night length described in the literature. Our results favour perennial ST and suggest assigning time-zones close to sun time to prevent social jetlag and sleep deprivation.

Updates and confounding factors in delayed sleep-wake phase disorder.

Delayed sleep-wake phase disorder (DSWPD) is a circadian rhythm sleep disorder characterised by a delay in the main sleep period, with patients experiencing difficulty getting to sleep and waking up at socially appropriate times. This often causes insomnia and compromised sleep, results in impairment to daytime function and is associated with a range of comorbidities. Besides interventions aimed at ameliorating symptoms, there is good evidence supporting successful phase advancement with bright light therapy or melatonin administration. However, no treatment to date addresses the tendency to phase delay, which is a common factor amongst the various contributing causes of DSWPD. Circadian phase markers such as core body temperature and circulating melatonin typically correlate well with sleep timing in healthy patients, but numerous variations exist in DSWPD patients that can make these unpredictable for use in diagnostics. There is also increasing evidence that, on top of problems with the circadian cycle, sleep homeostatic processes actually differ in DSWPD patients compared to controls. This naturally has ramifications for management but also for the current approach to the pathogenesis itself in which DSWPD is considered a purely circadian disorder. This review collates what is known on the causes and treatments of DSWPD, addresses the pitfalls in diagnosis and discusses the implications of current data on modified sleep homeostasis, making clinical recommendations and directing future research.

The dim light melatonin onset across ages, methodologies, and sex and its relationship with morningness/eveningness.

The onset of melatonin secretion, the dim light melatonin onset (DLMO), is a tool for determining the phase of the circadian timing system. Although small studies have investigated the impacts of age and methods of calculating DLMO, there is no DLMO reference range. In the current study, the saliva DLMO from 3579 participants from 121 published studies and plasma DLMO from 818 healthy controls from 31 studies (aged 3-73 years) were analyzed. In a subset of 53 papers (1749 participants), individual saliva DLMO and Morningness Eveningness Questionaire (MEQ) scores were obtained from authors or mined from publications and a reference range was constructed. Saliva DLMO was earliest in children to 10 years of age and latest around 20 years of age and thereafter advanced with age by 30 min in the oldest participants. Melatonin assay methods and DLMO calculation methods had little effect on the determination of the DLMO. Saliva DLMO was correlated (p < 0.001) with the MEQ score; lower MEQ scores were associated with later DLMO. MEQ scores increased with age, reflecting a tendency toward morningness. An evaluation of 14 saliva DLMO studies of clinically diagnosed patients living with delayed sleep-wake phase disorder (mean ages 20 to 31 years) revealed mean saliva DLMO within the reference range albeit at the late extreme. Peak plasma melatonin levels from 179 studies of healthy participants revealed a high degree of variability within studies and age groups, but only a small decline between the 20 and 50 years and lowest levels after 70 years.

Differences in psychosocial factors and sleep study findings between delayed sleep-wake phase disorder and hypersomnia in teenagers.

Central hypersomnia (HS) and delayed sleep-wake phase disorder (DSWPD) appear commonly in adolescents, and they severely reduce quality of life and have an enormous impact on academic performance and other aspects of development. Although these disorders are thought to be considerably different in etiology, it is sometimes difficult to distinguish them because of their similar clinical features. This study aimed to compare psychosocial factors and sleep study findings between HS and DSWPD in teenagers. The clinical data of 89 teenagers who visited the psychiatric section of the Sleep Medicine Center of Nihon University Itabashi Hospital from January 2013 to December 2019 were analyzed. Psychosocial factors were evaluated at the first visit, and polysomnography (PSG) and the multiple sleep latency test (MSLT) were performed for patients deemed to require definitive diagnosis. Compared with patients with HS, those with DSWPD had a higher rate of mother's employment, introversion, adjustment problems, events that triggered the disorder, concurrent mental disorders, habitual lateness, and difficulty attending school or work. PSG did not show any differences in sleep parameters between the two disorders, except for sleep latency. On the MSLT, sleep latency was shorter in those with HS on the second, third, and fourth tests. The present results suggest that focusing on psychosocial factors could be useful for differential diagnosis of the two disorders that appear commonly in adolescents.

Efficacy of agomelatine with cognitive behavioral therapy for delayed sleep-wake phase disorder in young adults: A randomized controlled study

ABSTRACT Background Delayed sleep-wake phase disorder (DSWPD) is common and easily misdiagnosed in young people, and to date, there is no evidence-based treatment. Purpose A nonblinded randomized controlled study evaluated the effect of agomelatine therapy (AT) and cognitive behavior therapy (CBT) on DSWPD in young adults. Methods Sixty adolescents and young adults (range = 19–24 years, mean = 22 years, 52% female) diagnosed with DSWPD were randomized to receive 4 weeks of agomelatine therapy with or without cognitive behavior therapy. Sleep diaries, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and World Health Organization wellbeing questionnaire (WHO-5) were measured pre-treatment and post-treatment. Results Agomelatine therapy for 4 weeks shifted the sleep-wake rhythm (p < .001) forward in both groups at the week 4 assessment. There were no significant differences in sleep onset (p = .099) and sleep offset (p = .959) between the CBT group and the no treatment (NT) group at the follow-up visits. However, significant differences were found in sleep duration (p = .002), sleep quality (p=0.005), sleep difficulties (p < .001), daytime sleepiness (p = .001), and wellbeing (p = .007) between groups. Conclusions The improvements were received largely through the sleep-promoting effects of agomelatine therapy, and combining with cognitive behavior therapy on maintenance of altered sleep rhythms might be feasible.

Delayed circadian rhythms and insomnia symptoms in obsessive-compulsive disorder

BackgroundAccumulating evidence implicates sleep and circadian rhythm disturbance in obsessive-compulsive disorder (OCD). However, a multimethod characterization of sleep and circadian rhythms in OCD, their association with symptom severity, and the functional relationship between these variables is lacking. MethodsThe present study measured multiple indicators of sleep and circadian rhythms in a sample of adults with OCD, adults without OCD, and healthy controls (n = 74). Participants completed measures of morningness-eveningness, delayed sleep-wake phase disorder (DSWPD), insomnia symptoms, and OCD symptoms, as well as one week of sleep monitoring via a sleep diary and actigraphy. ResultsDelayed circadian rhythms (higher eveningness, later mid-sleep timing, and higher rates of DSWPD) and higher insomnia symptoms were observed in those with OCD compared to healthy controls, as well as associations between delayed circadian rhythms and insomnia symptoms and OCD symptom severity across the full sample. Further, insomnia symptoms mediated the relationship between delayed circadian rhythms and OCD symptoms. In contrast, there were no links between total sleep time or sleep quality and OCD. LimitationsData collection during COVID-19 pandemic, correlational data, no physiological measure of circadian rhythms. ConclusionsThese findings highlight a robust association between delayed circadian rhythms and OCD and suggest insomnia symptoms may be one mechanism in this relationship. Sleep and circadian rhythm disturbance may be novel targets for OCD treatment.

The Effect of Light Therapy on Electroencephalographic Sleep in Sleep and Circadian Rhythm Disorders: A Scoping Review.

Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep–wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00–23:00 h) compared with afternoon light therapy (>4000 lx between 15:00–17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality.

Clinical effects of acupuncture on the treatment of delayed sleep wake phase disorder (DSWPD)

Background: Delayed sleep–wake phase disorder (DSWPD) is a circadian rhythm sleep disorder. People with DSWPD fall asleep approximately 2 to 6hours later than those with normal sleep patterns, negatively affecting their ability to learn and work. According to some randomized controlled trials, acupuncture can effectively treat sleep disorders; however, no study has focused specifically on DSWPD. We verified the efficacy of acupuncture in patients with DSWPD by designing an randomized controlled trials with a sufficient sample size, and formed the basis for an improved acupuncture treatment protocol. Method/Design: This protocol describes a randomized, single-site, double-blind, sham-controlled trial in which 84 eligible participants will be enrolled and randomly distributed to either the acupuncture group (n = 42) or the sham acupuncture group (n = 42) in a 1:1 proportion. Participants will receive 20 treatment sessions over eight consecutive weeks. Sleep quality was evaluated by using the Pittsburgh Sleep Quality Index. The sleep parameters recorded will be used to measure the secondary results using actigraphy, the Morningness-Eveningness Questionnaire, Insomnia Severity Index Scale, Epworth Sleepiness Scale, Beck Depression Inventory, and Beck Anxiety Inventory. Primary outcomes and actigraphy will be evaluated at baseline, week 4, week 8, and at the first and third month after treatment. Discussion: We hypothesize that the outcomes of the proposed study will determine that acupuncture is efficient and secure for the treatment on DSWPD. Evidence for its clinical use could be provided by this positive result. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000039450. Registered on October 28, 2020.

Decrease in Social Zeitgebers Is Associated With Worsened Delayed Sleep-Wake Phase Disorder: Findings During the Pandemic in Japan.

BackgroundDelay in sleep-wake rhythms was observed in the general population during the coronavirus disease 2019 (COVID-19) pandemic. Patients with delayed sleep-wake phase disorder (DSWPD) may have also experienced exacerbation of symptoms, but no studies have investigated this topic. In this study, we aimed to retrospectively examine the changes in symptoms of outpatients with DSWPD both before and during the pandemic and to identify the factors associated with the exacerbation of sleep-wake rhythms.MethodsWe included outpatients with DSWPD aged 16 years or older who visited the outpatient clinic due to sleep disorders between January and September 2020. Decreased social zeitgebers was defined as a reduction of 50% or more in the frequency of commuting to school or work during the COVID-19 pandemic. The severity of DSWPD was assessed using the clinical global impressions - severity of illness (CGI-S) at two points: before and during the pandemic. We defined the worsened, unchanged, and improved groups as those whose CGI-S scores worsened by at least one point, remained unchanged, and improved by at least one point, respectively. Multivariate logistic regression analysis was performed to determine the factors associated with worsened DSWPD symptoms.ResultsSixty patients with DSWPD were eligible for this study. Even before the pandemic, patients who were unemployed or did not attend school tended to show more severe DSWPD symptoms. During the pandemic, 27 patients belonged to the worsened group; 28 patients, unchanged group; and 5 patients, improved group. Decreased social zeitgebers (odds ratio [OR] = 6.668, 95% confidence interval [CI]: 1.653–26.891, p < 0.05) and comorbid mood disorders (OR = 8.876, 95% CI: 1.714–45.974, p < 0.05) showed independent significant associations with the worsening of DSWPD symptoms.ConclusionsDuring the pandemic, the symptoms of DSWPD tended to worsen. The obtained findings emphasize the importance of social zeitgebers, suggesting the need for external motivation in DSWPD treatment.

0211 A 10-week observational research study in individuals with delayed sleep-wake phase disorder (DSWPD) symptoms

Abstract Introduction We conducted an observational research study in suspected delayed sleep-wake phase disorder (DSWPD) participants. The objective was to measure sleep-wake patterns and to conduct exploratory genetic analyses to delineate the landscape of DSWPD. Methods We measured the sleep-wake patterns of participants by daily post-sleep diaries for 10 weeks. Participants also completed questionnaires on demographics, medical/surgical history, sleep history, and concomitant medications. Altogether, 119 participants were consented and 76 participants provided samples for whole genome sequencing. Results Sleep diary analysis confirmed delayed sleeping patterns in the study population. Midpoint of sleep was 4:50 AM (SD = 2:06) versus 3:06 AM (SD = 0:59) in controls, a statistically significant difference (t (df) = 6.57 (72.063); p ≤ 0.0001). Mean total sleep time (TST) was 6.88 h (SD = 1.35) versus 7.79 h (SD = 0.56) in controls, a statistically significant difference (t (df) = -5.38 (70.863); p ≤ 0.0001). This effect was driven by shorter participant-reported TST on work nights (6.33 h) versus free nights (7.22 h). Sleep latency was significantly later on work nights than free nights. Altogether 17% of participants reported at least one psychiatric condition.We observed an enrichment of the minisatellite 54bp (1: 7829913-7829966 (GRCh38)) variable number of tandem repeat (VNTR) PER3 rs57875989 4 allele. Significantly higher frequencies of the 4/4 and 4/5 variants were observed when compared to controls (n = 1937; recessive: OR 3.3, CI 2.1177 to 5.4304, p &amp;lt; 0.0001).We analyzed the putative loss-of-function and missense variants. We report on presence of cases with PER3 rs144178755 (NM_001289862:p.T1049), PER3 rs228696 (NM_001289861:p.L835P), and PER2 rs76355956 (NM_022817:p.V197M), among other rare nonsynonymous variants. We observed higher frequency of missense variants in core clock genes when compared to controls. Conclusion Sleep diary data confirmed significantly delayed sleep patterns, with more pronounced results during work nights and larger SDs across all sleep parameters, suggesting more variable sleep patterns. Genetic analysis confirmed these individuals are more likely to harbor variants within their core clock genes with enrichment of the VNTR variant, potentially leading to a pronounced delay in sleep period. Support (If Any) Vanda Pharmaceuticals Inc.

Sleep in adolescence: Considering family structure and family complexity

AbstractObjectivesTo investigate associations between family structure, family complexity, and sleep in adolescence.BackgroundFamily structure may be associated with sleep patterns and sleep problems among adolescents. Yet, research documenting this association has not captured the complexity of modern families and used crude measures of sleep.MethodThe youth@hordaland study (N = 8833) of adolescents aged 16–19 conducted in 2012 in Norway provided a detailed assessment of family structure, family complexity (i.e., living with half‐/stepsiblings), and multiple sleep parameters. Insomnia and delayed sleep–wake phase disorder (DSWPD) were defined in alignment with diagnostic criteria. Ordinary least squares and Poisson regression analyses were used to assess associations between family structure, family complexity, and sleep outcomes.ResultsAdolescents in joint physical custody (JPC) had more similar sleep parameters as peers in nuclear families than in single‐and stepparent families. Adolescents in single‐ and stepparent families had a higher risk of short sleep duration on weekdays, long sleep onset latency, long wake after sleep onset, oversleeping, insomnia, and DSWPD than peers in nuclear families. Family complexity was also associated with a higher risk of sleep problems, but the risk attenuated when considered jointly with family structure. Socioeconomic status and depressive symptoms partly attenuated the differences between the groups.ConclusionInequalities in sleep exist by family structure and, in part, family complexity. Despite alternating between two homes and often experiencing family complexity, sleep among adolescents in JPC was more similar to peers in nuclear families than in single‐ and stepparent families.

Circadian Rhythm Sleep Disorders: Genetics, Mechanisms, and Adverse Effects on Health.

Nearly all living organisms, from cyanobacteria to humans, have an internal circadian oscillation with a periodicity of approximately 24 h. In mammals, circadian rhythms regulate diverse physiological processes including the body temperature, energy metabolism, immunity, hormone secretion, and daily sleep-wake cycle. Sleep is tightly regulated by circadian rhythms, whereas a misalignment between the circadian rhythms and external environment may lead to circadian rhythm sleep disorders (CRSD). CRSD includes four main kinds of disorders: the advanced sleep-wake phase disorder (ASPD), the delayed sleep-wake phase disorder (DSPD), the irregular sleep-wake rhythm disorder and the non-24-h sleep-wake rhythm disorder. Recent studies have begun to shed light on the genetic basis of CRSD. Deciphering the genetic codes for ASPD and DSPD has so far been more successful than the other CRSDs, which allow for the development of animal models and understanding of the pathological mechanisms for these disorders. And studies from humans or animal models implicate CRSDs are associated with adverse health consequences, such as cancer and mental disorders. In this review, we will summarize the recent advances in the genetics, underlying mechanisms and the adverse effects on health of ASPD and DSPD.