Development and validation of the Japanese version of the Hyperarousal Scale.

BACKGROUND: The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers. METHODS: We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment). RESULTS: Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ2 (163) = 327.423, (p <  0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers. CONCLUSIONS: This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients.

A missense variant in PER2 is associated with delayed sleep-wake phase disorder in a Japanese population.

Delayed sleep-wake phase disorder (DSWPD) is a subtype of circadian rhythm sleep-wake disorders, and is characterized by an inability to fall asleep until late at night and wake up at a socially acceptable time in the morning. The study aim was to identify low-frequency nonsense and missense variants that are associated with DSWPD. Candidate variants in circadian rhythm-related genes were extracted by integration of genetic variation databases and in silico assessment. We narrowed down the candidates to six variants. To examine whether the six variants are associated with DSWPD, we performed an association study in 236 Japanese patients with DSWPD and 1436 controls. A low-frequency missense variant (p.Val1205Met) in PER2 showed a significant association with DSWPD (2.5% in cases and 1.1% in controls, P = 0.026, odds ratio (OR) = 2.32). The variant was also associated with idiopathic hypersomnia known to have a tendency toward phase delay (P = 0.038, OR = 2.07). PER2 forms a heterodimer with CRY, and the heterodimer plays an important role in the regulation of circadian rhythms. Val1205 is located in the CRY-binding domain of PER2 and was hypothesized to interact with CRY. The p.Val1205Met substitution could be a potential genetic marker for DSWPD.

A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia.

Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10-9, odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10-18) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.

New susceptibility variants to narcolepsy identified in HLA class II region.

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.

Behavioral symptoms and sleep problems in children with anxiety disorder.

BACKGROUND: Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorder. To identify promising behavioral targets for pediatric anxiety disorder therapy, we investigated the associations between specific sleep and behavioral problems. METHODS: We conducted retrospective reviews of 105 patients aged 4-12 years who met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (n = 33), separation anxiety disorder (n = 23), social phobia (n = 21), or obsessive compulsive disorder (n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems by the Spence Children's Anxiety Scale, Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children. RESULTS: Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delay and night waking but not with total sleep disturbance. Anxiety was correlated with bedtime resistance, night waking, and total sleep disturbance score. Oppositional defiance was correlated with bedtime resistance, daytime sleepiness, sleep onset delay, and most strongly with total sleep disturbance. On multiple regression analysis ODBI score had the strongest positive association with total sleep disturbance and the strongest negative association with total sleep duration. CONCLUSIONS: Sleep problems in children with anxiety disorders are closely related to anxiety and oppositional defiant symptoms.

Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study.

INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS: This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS: Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION: Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.

A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH. We performed a variation screening of the prepro-orexin/hypocretin and orexin receptors genes and an association study for IH in a Japanese population, with replication (598 patients and 9826 controls). We identified a rare missense variant (g.42184347T>C; p.Lys68Arg; rs537376938) in the cleavage site of prepro-orexin that was associated with IH (minor allele frequency of 1.67% in cases versus 0.32% in controls, P = 2.7 × 10-8, odds ratio = 5.36). Two forms of orexin (orexin-A and -B) are generated from cleavage of one precursor peptide, prepro-orexin. The difference in cleavage efficiency between wild-type (Gly-Lys-Arg; GKR) and mutant (Gly-Arg-Arg; GRR) peptides was examined by assays using proprotein convertase subtilisin/kexin (PCSK) type 1 and PCSK type 2. In both PCSK1 and PCSK2 assays, the cleavage efficiency of the mutant peptide was lower than that of the wild-type peptide. We also confirmed that the prepro-orexin peptides themselves transmitted less signaling through orexin receptors than mature orexin-A and orexin-B peptides. These results indicate that a subgroup of IH is associated with decreased orexin signaling, which is believed to be a hallmark of narcolepsy type 1.

Genome-wide association study of idiopathic hypersomnia in a Japanese population.

Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In contrast to narcolepsy type 1, which is a well-recognized hypersomnia, the etiology of IH remains poorly understood. No susceptibility loci for IH have been identified, although familial aggregations have been observed among patients with IH. Narcolepsy type 1 is strongly associated with human leukocyte antigen (HLA)-DQB1*06:02; however, no significant associations between IH and HLA alleles have been reported. To identify genetic variants that affect susceptibility to IH, we performed a genome-wide association study (GWAS) and two replication studies involving a total of 414 Japanese patients with IH and 6587 healthy Japanese individuals. A meta-analysis of the three studies found no single-nucleotide polymorphisms (SNPs) that reached the genome-wide significance level. However, we identified several candidate SNPs for IH. For instance, a common genetic variant (rs2250870) within an intron of PDE9A was suggestively associated with IH. rs2250870 was significantly associated with expression levels of PDE9A in not only whole blood but also brain tissues. The leading SNP in the PDE9A region was the same in associations with both IH and PDE9A expression. PDE9A is a potential target in the treatment of several brain diseases, such as depression, schizophrenia, and Alzheimer's disease. It will be necessary to examine whether PDE9A inhibitors that have demonstrated effects on neurophysiologic and cognitive function can contribute to the development of new treatments for IH, as higher expression levels of PDE9A were observed with regard to the risk allele of rs2250870. The present study constitutes the first GWAS of genetic variants associated with IH. A larger replication study will be required to confirm these associations. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-021-00349-2.

Decreased activity in the reward network of chronic insomnia patients.

In modern society, many people have insomnia. Chronic insomnia has been noted as a risk factor for depression. However, there are few functional imaging studies of the brain on affective functions in chronic insomnia. This study aimed to investigate brain activities induced by emotional stimuli in chronic insomnia patients. Fifteen patients with primary insomnia and 30 age and gender matched healthy controls participated in this study. Both groups were presented images of fearful, happy, and neutral expressions consciously and non-consciously while undergoing MRI to compare the activity in regions of the brain responsible for emotions. Conscious presentation of the Happy-Neutral contrast showed significantly lower activation in the right orbitofrontal cortex of patients compared to healthy controls. The Happy-Neutral contrast presented in a non-conscious manner resulted in significantly lower activation of the ventral striatum, right insula, putamen, orbitofrontal cortex and ventral tegmental area in patients compared to healthy controls. Our findings revealed that responsiveness to positive emotional stimuli were decreased in insomniac patients. Specifically, brain networks associated with rewards and processing positive emotions showed decreased responsiveness to happy emotions especially for non-conscious image. The magnitude of activity in these areas also correlated with severity of insomnia, even after controlling for depression scale scores. These findings suggest that insomnia induces an affective functional disorder through an underlying mechanism of decreased sensitivity in the regions of the brain responsible for emotions and rewards to positive emotional stimuli.

Current state of hypnotic use disorders: Results of a survey using the Japanese version of Benzodiazepine Dependence Self-Report Questionnaire.

AIMS: Benzodiazepine receptor agonists (BZ-RAs) are frequently prescribed to treat insomnia; however, their long-term use is not recommended. To introduce an appropriate pharmaco-therapy, the current state and background factors of BZ-RAs' dependence must be elucidated. In this study, we developed a Japanese version of the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ-J) and conducted a study of BZ-RAs' use disorder. METHODS: The Bendep-SRQ-J was created with permission from the original developer. Subjects were inpatients and outpatients receiving BZ-RAs between 2012 and 2013. Clinical data collected were Bendep-SRQ-J scores, sleep disorders for which BZ-RAs were prescribed, physical comorbidities, psychotropic drugs, and lifestyle factors. Logistic analysis was performed to extract factors associated with severe symptoms. RESULTS: Of the 707 patients prescribed BZ-RAs, 324 had voluntarily tapered or discontinued their drugs. Logistic analysis showed that the total number of drugs administered in the last 6 months correlated with both worsening of symptoms or conditions. This was more notable among younger patients, and the proportion of patients with severe symptoms or conditions increased with the increasing number of drugs. CONCLUSION: Using the Bendep-SRQ-J, we elucidated the current state of BZ-RA dependence. Nearly half of the patients were non-compliant. The proportion of patients with severe symptoms or disease conditions increased with the increase in the number of drugs administered. These findings highlight the need for clinicians to be aware of the likelihood of benzodiazepine dependence, especially in young patients and patients prescribed multiple hypnotics.

[Bright light therapy].

Bright light is a treatment of choice for seasonal affective disorder. Other indications for bright light therapy have also been tested. These include circadian rhythm sleep disorders, early-morning awakening or sleep-maintenance insomnia in elders and behavioral disturbance or insomnia in organic dementia. In these sleep disorders, the pattern of sleep-wake is misaligned with the patient's circadian system or the external environment, resulting in insomnia. Appropriately-timed exposure to bright light can shift the sleep-wake cycle to earlier or later times, in order to correct for misalignment between the circadian system and the desired sleep-wake schedule. Evidence of the efficacy of bright light was so limited. Further research is needed to determine guidelines for the appropriate timing and safe use of bright light therapy.

A community intervention trial of multimodal suicide prevention program in Japan: a novel multimodal community intervention program to prevent suicide and suicide attempt in Japan, NOCOMIT-J.

BACKGROUND: To respond to the rapid surge in the incidence of suicide in Japan, which appears to be an ongoing trend, the Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) have launched a multimodal community-based suicide prevention program, NOCOMIT-J. The primary aim of this study is to examine whether NOCOMIT-J is effective in reducing suicidal behavior in the community. METHODS/DESIGN: This study is a community intervention trial involving seven intervention regions with accompanying control regions, all with populations of statistically sufficient size. The program focuses on building social support networks in the public health system for suicide prevention and mental health promotion, intending to reinforce human relationships in the community. The intervention program components includes a primary prevention measures of awareness campaign for the public and key personnel, secondary prevention measures for screening of, and assisting, high-risk individuals, after-care for individuals bereaved by suicide, and other measures. The intervention started in July 2006, and will continue for 3.5 years. Participants are Japanese and foreign residents living in the intervention and control regions (a total of population of 2,120,000 individuals). DISCUSSION: The present study is designed to evaluate the effectiveness of the community-based suicide prevention program in the seven participating areas. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000460.

Lack of association between PER3 variable number tandem repeat and circadian rhythm sleep-wake disorders.

Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by disturbed sleep-wake patterns. We genotyped a PER3 variable number tandem repeat (VNTR) in 248 CRSWD individuals and 925 controls and found no significant association between the VNTR and CRSWDs or morningness-eveningness (diurnal) preferences in the Japanese population. Although the VNTR has been associated with circadian and sleep phenotypes in some other populations, the polymorphism may not be a universal genetic marker.

Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan.

OBJECTIVES: An insomnia characterized by nighttime symptoms and daytime impairment is common. GABA-A receptor agonist (GABAA-RA) treatment is often used, but long-term use is controversial due to the poor risk-benefit ratio resulting from drug dependence and potential cognitive impairment. This study evaluated the effectiveness of add-on cognitive behavioral therapy for insomnia (CBT-I) and GABAA-RA dose-tapering in patients with primary insomnia resistant to pharmacotherapy. METHODS: This randomized, multicenter, two-arm, parallel-group study compared CBT-I and treatment as usual (TAU) in patients with persistent primary insomnia despite GABAA-RA treatment. Screening was based on sleep diary entries, with ≥31-min sleep latency or wake after sleep onset, occurring ≥3 times in a week and total score of ≥8 on the Insomnia Severity Index (ISI). Primary outcome measures were severity of insomnia and GABAA-RA tapering rate. RESULTS: A total of 51 patients were randomized and 49 patients were analyzed (CBT-I; n = 23, TAU; n = 26). A mixed-effects repeated-measures model revealed significant improvement in insomnia symptoms (ISI score) during the post-intervention (PI) and follow-up (FU) periods in the CBT-I versus the TAU group (PI; 10.91 vs. 14.33, p < 0.05, FU; 10.17 vs. 14.34, p < 0.01). GABAA-RA tapering rate approached 30% during follow-up in the CBT-I group; no significant intergroup difference was observed. CONCLUSION: Add-on CBT-I improved insomnia symptoms that were unresponsive to GABAA-RA therapy. No effect on tapering rate was observed in this study. CBT-I may promote dose reduction by optimizing the protocol and duration of treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000014297.

Reliability and validity of a brief sleep questionnaire for children in Japan.

BACKGROUND: There is a dearth of sleep questionnaires with few items and confirmed reliability and validity that can be used for the early detection of sleep problems in children. The aim of this study was to develop a questionnaire with few items and assess its reliability and validity in both children at high risk of sleep disorders and a community population. METHODS: Data for analysis were derived from two populations targeted by the Children's Sleep Habits Questionnaire (CSHQ): 178 children attending elementary school and 432 children who visited a pediatric psychiatric hospital (aged 6-12 years). The new questionnaire was constructed as a subset of the CSHQ. RESULTS: The newly developed short version of the sleep questionnaire for children (19 items) had an acceptable internal consistency (0.65). Using the cutoff value of the CSHQ, the total score of the new questionnaire was confirmed to have discriminant validity (27.2 ± 3.9 vs. 22.0 ± 2.1, p < 0.001) and yielded a sensitivity of 0.83 and specificity of 0.78 by receiver operator characteristic curve analysis. Total score of the new questionnaire was significantly correlated with total score (r = 0.81, p < 0.001) and each subscale score (r = 0.29-0.65, p < 0.001) of the CSHQ. CONCLUSIONS: The new questionnaire demonstrated an adequate reliability and validity in both high-risk children and a community population, as well as similar screening ability to the CSHQ. It could thus be a convenient instrument to detect sleep problems in children.

Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases.

STUDY OBJECTIVES: The objective of this study was to clarify the clinical features of sighted patients with non-24-hour sleep-wake syndrome. DESIGN: Clinical analyses of consecutive patients suffering from non-24-hour sleep-wake syndrome. SETTING: The sleep disorders clinic at Kohnodai Hospital, National Center of Neurology and Psychiatry, Japan. PATIENTS: Fifty-seven patients who were diagnosed consecutively as having non-24-hour sleep-wake syndrome between 1991 and 2001 were included in the study. MEASUREMENTS AND RESULTS: The clinical features and sleep characteristics of the patients were analyzed. A semistructured psychiatric interview that included the criteria for Axis I or II disorders of Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised was conducted, and relationships between psychiatric problems and non-24-hour sleep-wake syndrome were analyzed. The patient cohort included 41 (72%) men and 16 (28%) women. The onset of non-24-hour sleep-wake syndrome had occurred during the teenage years in 63% of the cohort, and the mean ( +/-SD) period of the sleep-wake cycle was 24.9 +/- 0.4 hours (range 24.4-26.5 hours). The mean sleep length of the patients was 9.3 +/- 1.3 hours, and 44% of them had a sleep length of between 9 and 10 hours. Psychiatric disorders had preceded the onset of non-24-hour sleep-wake syndrome in 16 patients (28%); of the remaining 41 patients, 14 (34%) developed major depression after the onset of non-24-hour sleep-wake syndrome. CONCLUSIONS: These results represent the first detailed clinical review of a relatively large number of sighted patients with non-24-hour sleep-wake syndrome.

Diurnal fluctuation of time perception under 30-h sustained wakefulness.

Previous studies have reported that time perception in humans fluctuates over a 24-h period. Behavioral changes seem to affect human time perception, so that the fluctuation in human time perception may be the result of such changes due to self-determined activities. Recently, we carried out a study in which a healthy human cohort was asked to perform simultaneously loaded cognitive tasks under controlled conditions, and found that time perception decreased linearly from morning to evening. In addition, the variations in time perception were not a consequence of behavioral changes. It remains to be elucidated whether diurnal variations in time perception are a consequence of circadian rhythm or of some homeostatic changes that are attributable to accumulated wake time. The effects of circadian rhythm on time perception were investigated in eight healthy young male volunteers by conducting 10-s time production tasks under 30-h constant-routine conditions. Core body temperature and serum melatonin and cortisol levels were measured during the course of the study. Produced time exhibited a diurnal variation and was strongly correlated with circadian variations in core body temperature and serum melatonin levels. These results suggest that human short-term time perception is under the influence of the circadian pacemaker.

Association between delayed bedtime and sleep-related problems among community-dwelling 2-year-old children in Japan.

BACKGROUND: Although delayed sleep timing causes many socio-psycho-biological problems such as sleep loss, excessive daytime sleepiness, obesity, and impaired daytime neurocognitive performance in adults, there are insufficient data showing the clinical significance of a 'night owl lifestyle' in early life. This study examined the association between habitual delayed bedtime and sleep-related problems among community-dwelling 2-year-old children in Japan. METHODS: Parents/caregivers of 708 community-dwelling 2-year-old children in Nishitokyo City, Tokyo, participated in the study. The participants answered a questionnaire to evaluate their child's sleep habits and sleep-related problems for the past 1 month. RESULTS: Of the 425 children for whom complete data were collected, 90 (21.2%) went to bed at 22:00 or later. Children with delayed bedtime showed significantly more irregular bedtime, delayed wake time, shorter total sleep time, and difficulty in initiating and terminating sleep. Although this relationship indicated the presence of sleep debt in children with delayed bedtime, sleep onset latency did not differ between children with earlier bedtime and those with delayed bedtime. Rather, delayed bedtime was significantly associated with bedtime resistance and problems in the morning even when adjusting for nighttime and daytime sleep time. CONCLUSIONS: Even in 2-year-old children, delayed bedtime was associated with various sleep-related problems. The causal factors may include diminished homeostatic sleep drive due to prolonged daytime nap as well as diurnal preference (morning or night type) regulated by the biological clock.