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.

Metabolic-Syndrome-Related Comorbidities in Narcolepsy Spectrum Disorders: A Preliminary Cross-Sectional Study in Japan.

Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are thought to be a disease continuum known as narcolepsy spectrum disorders (NSDs). This study aimed to assess the prevalence of and factors associated with metabolic-syndrome-related disorders (MRDs) among patients with NSD. Japanese patients with NSD (NT1, n = 94; NT2, n = 83; and IH, n = 57) aged ≥35 years were enrolled in this cross-sectional study. MRD was defined as having at least one of the following conditions: hypertension, diabetes, or dyslipidemia. Demographic variables and MRD incidence were compared among patients in the respective NSD categories. Multivariate logistic regression analysis was used to investigate the factors associated with MRDs. Patients with NT1 had a higher body mass index (BMI) and incidence of MRD than that had by those with NT2 or IH. Age, BMI, and the presence of OSA were significantly associated with the incidence of MRD in NSDs. Age and BMI in NT1, BMI and human leukocyte antigen (HLA)-DQB1*06:02 positivity in NT2, and only age in IH were factors associated with the incidence of MRD. Obesity should be carefully monitored in narcolepsy; however, NT2 with HLA-DQB1*06:02 positive should be followed up for the development of MRD even without obesity.

Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep.

Sleep terrors are a non-rapid eye movement (NREM) sleep-related parasomnia characterized by abrupt terror with a frightening scream. However, it remains unknown whether sleep terrors occur only from NREM sleep. We evaluated 3 cases of a sleep terrors-like parasomnia that occurred exclusively during arousals from rapid eye movement (REM) sleep. These parasomnia events occurred at REM sleep-wake transitions, manifesting with screaming or crying, similar to sleep terrors, without alertness or clear orientation. The patients were all young-adult females without notable medical conditions. REM sleep behavior disorder and nocturnal frontal lobe epilepsy were not detected based on their video-polysomnographic findings. These 3 cases should be provisionally diagnosed as "Parasomnia, Unspecified" according to the International Classification of Sleep Disorders, third edition; however, the phenomenological diagnosis is proposed to be "Disorders of Arousal from REM Sleep." Our reported cases indicate that sleep terrors may also arise from REM sleep. CITATION: Futenma K, Inoue Y, Saso A, Takaesu Y, Yamashiro Y, Matsuura M. Three cases of parasomnias similar to sleep terrors occurring during sleep-wake transitions from REM sleep. J Clin Sleep Med. 2022;18(2):669-675.

Association of sleep duration on workdays or free days and social jetlag with job stress.

AIM: The aim of this study was to investigate the impact of sleep problems on job stress in office workers. METHODS: This study included 4645 office workers from 29 companies who completed the study questionnaires between April 2017 and April 2019 in Japan. Sleep duration was assessed based on the participants' subjective sleep schedule on workdays and free days. The midpoint of sleep on free days (sleep-corrected) and social jetlag were calculated in accordance with the Munich Chronotype Questionnaire. To assess job stress, we used the 57-item Brief Job Stress Questionnaire. RESULTS: Multivariate logistic regression analysis revealed that the following factors were significantly associated with high job stress in office workers: a sleep duration <6 h on workdays (OR = 1.77, 95% CI = 1.46-2.15, P < 0.001), a sleep duration <6 h on free days (OR = 1.40, 95% CI = 1.05-1.87, P = 0.022), a sleep duration of at least 8 h on free days (OR = 1.31, 95% CI = 1.06-1.60, P = 0.011), and more than 2 h of social jetlag (OR = 1.33, 95% CI = 1.04-1.70, P = 0.022). CONCLUSION: This study suggests that insufficient sleep, long sleep durations on free days, and social jetlag may be associated with high job stress in office workers.

Reliability and validity of the Japanese version of the Biological Rhythms Interview of assessment in neuropsychiatry-self report for delayed sleep-wake phase disorder.

OBJECTIVE: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder. METHODS: We enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD. RESULTS: The 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD. CONCLUSIONS: The results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.

Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients With Bipolar Disorder: A Prospective 48-Week Study.

OBJECTIVE: Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients. METHODS: One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes. RESULTS: Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001). CONCLUSIONS: Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.

Circadian rhythm sleep-wake disorders as predictors for bipolar disorder in patients with remitted mood disorders.

BACKGROUND: Circadian rhythm dysfunction is thought to play a key role in the pathogenesis of bipolar disorder (BD). We focused on circadian rhythm sleep-wake disorders (CRSWD) as possible predictors for bipolar disorder in patients with remitted mood disorders. METHOD: One hundred four BD (41 type I and 63 type II) outpatients and 73 age- and sex-matched major depressive disorder (MDD) outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of the disorder, and family history of psychiatric disorders. Severity of mood status was evaluated by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview and sleep logs based on the International Classification of Sleep Disorders, third edition. RESULTS: The rate of CRSWD in BD subjects was significantly higher than that in MDD subjects (33.7% vs 9.6%; P < 0.001). A multiple logistic regression analysis revealed that comorbid CRSWD (OR = 3.35, 95% CI = 1.24 - 9.07; P = 0.018), two or more previous mood episodes within the past year (OR = 3.57, 95% CI = 1.10 - 11.63; P = 0.035), and antidepressant-related switch to mania/hypomania (OR = 10.01, 95% CI = 1.20 - 83.52; P = 0.033) were significantly associated with BD in patients with remitted mood disorders. CONCLUSION: CRSWD, as well as other factors, could be diagnostic predictors for BD in patients with remitted mood disorders. Combinations of these factors might be useful for predicting a BD diagnosis among the mood disorders in a clinical setting.

Association between the high-dose use of benzodiazepines and rehospitalization in patients with schizophrenia: a 2-year naturalistic study.

BACKGROUND: High-dose use of benzodiazepines (BZPs) reportedly causes adverse effects on cognitive function and quality of life in patients with schizophrenia. However, effects of BZPs on the clinical course of schizophrenia have not been clarified. This study was set out to investigate the association between BZPs and rehospitalization of patients with schizophrenia. METHODS: In this retrospective study, patients with schizophrenia who were discharged from Tokyo Medical University Hospital between January 2009 and February 2012 were eligible as subjects. One hundred and eight patients who continued treatment for >2 years after hospital discharge were included in this study. Clinical characteristics, doses of prescribed medication such as BZPs and antipsychotics, and Global Assessment of Functioning scores at discharge were investigated. The primary outcome was rehospitalization of patients for any reason. RESULTS: In a total of 108 subjects with schizophrenia, 44 subjects (40.7%) experienced rehospitalization during the 2-year study period. A multivariate analysis by the Cox proportional hazards model revealed that low educational history (hazard ratio =2.43, P=0.032), younger onset age of schizophrenia (hazard ratio =2.10, P=0.021), and higher diazepam-equivalent dose (hazard ratio =6.53, P=0.011) were significantly associated with the time to rehospitalization after hospital discharge. CONCLUSION: The results of this study suggest that high-dose use of BZPs at discharge in patients with schizophrenia might be associated with a shorter time to rehospitalization.

Later sleep schedule and depressive symptoms are associated with usage of multiple kinds of hypnotics.

OBJECTIVE: Usage of high doses of hypnotics possibly causes various adverse events. However, the risk factors of using multiple kinds of hypnotics have been inconclusive. To clarify this, we conducted a web-based cross-sectional questionnaire survey on the Japanese adult population. METHODS: A cross-sectional Internet-linked survey was conducted on 10,016 individuals and 1030 participants (10.3%) having subjective insomnia proceeded to subsequent analyses. The analyzed subjects were categorized into non-users of hypnotics (n = 833; 80.9%), users of a single kind of hypnotic (n = 96; 9.3%), and users of multiple kinds of hypnotics (n = 101; 9.8%). The descriptive variables including demographic data, scores of Center for Epidemiological Studies Depression Scale (CES-D), Short Form-8 Health-Related Quality of Life [QOL (SF-8)], Pittsburgh Sleep Quality Index (PSQI), and other parameters were compared among the groups. RESULTS: The users of multiple kinds of hypnotics had the highest mean score of CES-D, the lowest mental component summary of QOL (SF-8), and the latest sleep schedule among the three groups (p < 0.001). Logistic regression analyses revealed that sex (female: OR = 2.38; p < 0.001) and age (≥43 years old: OR = 2.61; p < 0.001) were independently associated with use of a single kind of hypnotic, while later sleep schedule (midpoint of sleep ≥5:30 a.m.: OR = 2.26; p < 0.001) and higher CES-D score (≥16 points: OR = 2.41; p < 0.001) were independently associated with use of multiple kinds of hypnotics. CONCLUSIONS: Characteristics of users of multiple kinds of hypnotics were different from those of users of a single kind of hypnotic.

Prevalence of Circadian Rhythm Sleep-Wake Disorders and Associated Factors in Euthymic Patients with Bipolar Disorder.

Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients.

Prevalence of and Factors Associated With Sleep-Related Eating Disorder in Psychiatric Outpatients Taking Hypnotics.

OBJECTIVE: To clarify the prevalence and clinical features of sleep-related eating disorder (SRED) in psychiatric outpatients taking hypnotics as well as factors associated with the disorder. METHODS: From February 1, 2012, to February 29, 2012, a cross-sectional study was undertaken. A questionnaire addressing demographics, the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), presence of abnormal behavior during sleep focusing on SRED and sleepwalking, and duration of hypnotic medication and subjective side effects of the drug was distributed to psychiatric outpatients who were taking hypnotics at the time of the survey. RESULTS: Of 1,318 patients taking hypnotics, 1,048 patients (79.5%) provided valid responses, and 88 of them (8.4%) had experienced SRED. The SRED group was significantly younger, had a significantly higher total PSQI score, and took higher bedtime diazepam-equivalent doses of hypnotics than the non-SRED group (P < .01 for all comparisons). In the SRED group, subjective side effects due to hypnotics were present at significantly higher proportions than in the non-SRED group. Multiple logistic regression analysis showed that younger age (adjusted odds ratio [aOR] = 0.98, 95% CI = 0.96-0.99, P = .021), taking 2 or more kinds of antipsychotics (aOR = 3.41, 95% CI = 1.93-6.05, P < .001), and the bedtime diazepam-equivalent dose of a hypnotic (aOR = 1.03, 95% CI = 1.01-1.05, P = .039) were significantly associated with the experience of SRED. CONCLUSION: The prevalence of SRED in psychiatric outpatients taking hypnotics is elevated, particularly in younger patients, and the hypnosedative effects of the drugs could be responsible for the occurrence of the disorder in this population.

A preliminary study on the relationships between diurnal melatonin secretion profile and sleep variables in patients emergently admitted to the coronary care unit.

To clarify the significance of melatonin secretion under intensive care conditions, we investigated melatonin secretion profiles and sleep parameters of 23 patients just after admission to the coronary care unit (CCU) and 19 age-matched controls. Sleep parameters were evaluated by actigraphy, and melatonin secretion was assessed by measuring the urinary 6-sulphatoxy melatonin (6-SMT). 6-SMT secretion was lower and nocturnal sleep parameters were less satisfactory in the subjects than those in the controls, and there were positive correlations between these variables, particularly in the subject patients. The lowered melatonin secretion might be involved in the mechanism of insomnia in CCU patients.

Impact of hypnotics use on daytime function and factors associated with usage by female shift work nurses.

OBJECTIVE: We investigated quality of life (QOL) and work performance of hypnotics users, and explored the factors associated with multiple hypnotics usage in shift work nurses. METHODS: We conducted a questionnaire-based, cross-sectional survey on nurses in university hospitals. We analyzed responses from 1202 nurses; 997 were female shift work nurses (82.9%), including 696 and 281 two- and three-shift workers, respectively. RESULTS: The rate of hypnotics use was 10% (6.9% were single hypnotic users and 3.1% were multiple hypnotics users). The rate of insomnia did not differ between the single and multiple hypnotics users. However, multiple hypnotics users showed lower QOL, more severe depressive symptoms, and greater frequencies of work-related errors than those using a single hypnotic. A multiple logistic regression analysis revealed that age ≥27 years, presence of depression, eveningness chronotype, and presence of insomnia symptoms were significantly associated with hypnotics use. On the other hand, only the existence of shift work disorder (SWD) was significantly associated with usage of multiple hypnotics. CONCLUSIONS: The present study suggested that usage of multiple hypnotics is not beneficial for relieving insomnia or for keeping better QOL in shift work nurses. It would be desirable to explore the causal relationship between SWD and multiple hypnotics use in a future longitudinal study.

Internet-based survey of factors associated with subjective feeling of insomnia, depression, and low health-related quality of life among Japanese adults with sleep difficulty.

BACKGROUND: This study was conducted to determine what symptom components or conditions of insomnia are related to subjective feelings of insomnia, low health-related quality of life (HRQOL), or depression. METHOD: Data from 7,027 Japanese adults obtained using an Internet-based questionnaire survey was analyzed to examine associations between demographic variables and each sleep difficulty symptom item on the Pittsburgh Sleep Quality Index (PSQI) with the presence/absence of subjective insomnia and scores on the Short Form-8 (SF-8) and Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Prevalence of subjective insomnia was 12.2% (n = 860). Discriminant function analysis revealed that item scores for sleep quality, sleep latency, and sleep medication use on the PSQI and CES-D showed relatively high discriminant function coefficients for identifying positivity for the subjective feeling of insomnia. Among respondents with subjective insomnia, a low SF-8 physical component summary score was associated with higher age, depressive state, and PSQI items for sleep difficulty and daytime dysfunction, whereas a low SF-8 mental component summary score was associated with depressive state, PSQI sleep latency, sleeping medication use, and daytime dysfunction. Depressive state was significantly associated with sleep latency, sleeping medication use, and daytime dysfunction. CONCLUSION: Among insomnia symptom components, disturbed sleep quality and sleep onset insomnia may be specifically associated with subjective feelings of the disorder. The existence of a depressive state could be significantly associated with not only subjective insomnia but also mental and physical QOL. Our results also suggest that different components of sleep difficulty, as measured by the PSQI, might be associated with mental and physical QOL and depressive status.