Melatonin Treatment of Circadian Rhythm Sleep-Wake Disorder in Obese Children Affects the Brain-Derived Neurotrophic Factor Level.

BACKGROUND: Previous studies proved that the brain-derived neurotrophic factor (BDNF) is correlated with sleep regulation, yet how BDNF functions and reacts in the melatonin treatment of circadian rhythm sleep-wake disorder (CRSWD) among obese children remain enigmatic. Focusing on CRSWD in obese children, this study monitored their sleep efficiency and serum BDNF level changes during the treatment of melatonin. METHODS: In total, 35 obese children diagnosed with CRSWD were included in this study and administrated melatonin (3 mg/night) for 3 months. Blood samples were collected 24 hours before and after the treatment (08:00, 12:00, 16:00, 20:00, 24:00, and 04:00). Subsequently, the plasma melatonin level and serum BDNF level were measured by enzyme-linked immunosorbent assay. Sleep parameters, including sleep quality, Pittsburgh Sleep Quality Index as well as melatonin and BDNF levels before and after treatment, were recorded to profile the effectiveness and safety of melatonin treatment. RESULTS: Melatonin treatment increased plasma melatonin concentration and restored circadian rhythm. Besides, the serum BDNF level showed a significant increase, representing a strong positive correlation with melatonin concentration (p = 0.026). Patients experienced much-improved sleep efficiency (P < 0.001), with longer actual sleep time (P < 0.001), shorter sleep onset latency, and fewer awakenings after treatment (P < 0.001). Besides, melatonin was well tolerated by patients without producing severe side effects. CONCLUSION: Melatonin treatment effectively improved CRSWD among obese children with their serum BDNF levels increased, indicating that BDNF is a key regulator in CRSWD in obese children. This study may offer theoretical support for melatonin treatment of CRSWD in obese children.

Depressed mood and repetitive negative thinking in Delayed Sleep-Wake Phase Disorder: Treatment effects and a comparison with good sleepers.

Circadian dysregulation and depressed mood commonly co-occur in young people, yet mechanisms linking Delayed Sleep-Wake Phase disorder (DSWPD) with depression are poorly understood. The present study aimed to examine the role of repetitive negative thinking (RNT), by comparing sleep, RNT and depressive symptomology between 40 'good' sleeping young people and 63 with DSWPD, with (n = 30) and without (n = 33) self-reported doctor-diagnosed depression. Secondary analysis from a randomised controlled trial was also undertaken to observe changes in depressive symptoms and RNT as a result of treatment for DSWPD. The 60 young people with DSWPD (mean [SD] age of 15.9 [2.2] years, 63% female) received either short (green) or long (red) wavelength bright light therapy (BLT) over 3 weeks. Cross-sectional baseline comparisons revealed an escalating pattern of worse sleep, more RNT and higher depressed mood scores in the DSWPD young people compared to good sleepers. Across all participants, RNT accounted for the associations between sleep-onset difficulties and depressed mood at baseline. Symptoms of depression, RNT and sleep onset difficulties in DSWPD individuals significantly improved after treatment (d = 0.47-0.65) and at the 1- (d = 0.43-1.00) and 3-month follow-up (d = 0.39-1.38), yet there were no differences between short- and long-wavelength BLT. Results provide preliminary evidence that RNT may link delayed sleep phase with depression. BLT conferred sleep benefits, but also improvements in depressed mood and RNT, and thus represents a potentially cost-effective strategy for young people experiencing delayed sleep phase and low mood.

Evaluation and Management of Sleep and Circadian Rhythm Disturbance in Cancer.

OPINION STATEMENT: Sleep and circadian rhythm disturbance are among the most commonly experienced symptoms in patients with cancer. These disturbances occur throughout the spectrum of cancer care from diagnosis, treatment, and long into survivorship. The pathogenesis of these symptoms and disturbances is based on common inflammatory pathways related to cancer and its' treatments. The evaluation of sleep and circadian disorders requires an understanding of how these symptoms cluster with other cancer-related symptoms and potentiate each other. A thorough evaluation of these symptoms and disorders utilizing validated diagnostic tools, directed review of clinical information, and diagnostic testing is recommended. Treatment of sleep and circadian disturbance in cancer patients should be based on the findings of a detailed evaluation, including specific treatment of primary sleep and circadian disorders, and utilize integrative and personalised management of cancer-related symptoms through multiple pharmacologic and non-pharmacologic modalities. Recognition, evaluation, and treatment of sleep and circadian rhythm disturbance in cancer may lead to improved symptom management, quality of life, and outcomes.

The prevalence of excessive sleepiness is higher in shift workers than in patients with obstructive sleep apnea.

Excessive daytime sleepiness (EDS) is a common feature among shift workers as well as in obstructive sleep apnea (OSA) patients. There are several important accidents related to sleep disturbances causing EDS. The aim of this study was to evaluate EDS in a group of shift workers (regular rotating) from civil aviation and to compare them with OSA patients (n = 300) and with a group of regular workers (RW) (n = 140). Our sample was composed of 730 working-age individuals (aged 18-67 years). The regular rotating shift workers (SW) sample was composed of 290 aeronautical mechanics. EDS was evaluated with the Epworth Sleepiness Scale (ESS) and defined as a score ≥ 11. The prevalence value obtained for the EDS of RW was 37.1%, for SW it was 60.7% and for OSA patients it was 40.7%. A logistic regression model for EDS in a subsample composed of men and matched for age and BMI, controlling for self-reported sleep duration, showed an increased risk of EDS for SW (OR = 3.91, p = .001), with the RW group as reference. OSA patients did not differ from RW on EDS levels. This study emphasizes the presence of EDS in a shift work group of civil aviation professionals, which exceeded the EDS level of a positive control group of OSA patients. Sleep hygiene education for companies' workers and management is important and mitigation strategies should be implemented to reduce excessive sleepiness among workers.

Carotid intimal medial thickness in rotating night shift is related to IL1ß/IL6 axis.

BACKGROUND AND AIMS: Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors. METHODS AND RESULTS: We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1ß levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016). CONCLUSIONS: Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1ß/IL6 citokine axis connected to sleep disturbances.

Excessive sleepiness in shift work disorder: a narrative review of the last 5 years.

INTRODUCTION: Shift work sleep disorder (SWSD), also known as shift work disorder (SWD), is a circadian rhythm sleep disorder characterized by insomnia and/or excessive sleepiness, associated with a recurring work schedule that overlaps the usual time designated for sleeping. PURPOSE: This article aims to provide a narrative review of the pharmacological trials conducted on SWD in the last 5 years, to better address safety and health issues inherent to this disorder. METHODS: An electronic literature search was conducted using PubMed. All eligible randomized controlled trials (RCTs) and cross-over RCTs with employees undertaking shift work (including night shifts) were considered, yielding three articles. RESULTS: All three studies showed the efficacy of armodafinil in improving subjective and objective sleepiness, clinical conditions, and global functioning regardless of shift duration. Both performance and driving simulator performance tests administered during the night shift bore better results following armodafinil administration than after placebo. However, armodafinil only reduced subjective disability in individuals working more than 9 h; furthermore, even after armodafinil, alertness was reduced but not normalized. CONCLUSION: These studies underscore the importance of preventing and/or minimizing disturbances due to shift work. This may be achieved through various strategies, such as the employer's commitment to adopt ergonomic criteria in shift design and to implement work-environment interventions like controlled bright light. Health personnel is of pivotal importance to detect potential factors of intolerance to shift work or early symptoms of SWD. Additional and improved studies are needed to further evaluate the effectiveness and safety of both pharmacological and non-pharmacological interventions.

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.

Excessive daytime sleepiness in obstructive sleep apnea: implications for driving licenses.

PURPOSE: Excessive daytime sleepiness (EDS) while driving is a major international public health issue resulting in a more than doubled risk of motor vehicle accidents (MVAs). Obstructive sleep apnea (OSA) is the most frequent medical cause of EDS. Therefore, the European Union Directive 2014/85/EU determined that "untreated moderate to severe OSA coincident with EDS constitutes a medical disorder leading to unfitness to drive." The paper aims are to provide a brief review of sleepiness and its implications for driving safety, as well as to describe the subjective and objective methods to accurately evaluate EDS in order to assess fitness to drive in patients with OSA. METHODS: We examined databases including PubMed, Medline, and EMBASE using the search terms "sleepiness at the wheel, excessive daytime sleepiness, sleepiness measure, sleep-wake cycle, obstructive sleep apnea, driving license, fitness to drive." RESULTS: Significant interindividual variability in EDS exists in patients with comparable severity of OSA. Objective methods of measuring EDS are too expensive and time consuming to be suitable for the certification of driving licenses. The reliability of subjective methods depends upon the clinical setting and subjective tools assess only limited aspects of EDS. Objective measures, such as biochemical biomarkers, must, therefore, support subjective methods. CONCLUSIONS: Extensive data have supported different subjective and objective methods for the appraisal of EDS in patients with OSA depending upon the clinical and experimental setting. Challenges remain to determine an appropriate tool for the evaluation of fitness to drive.

Assessment and treatment of sleep problems in bipolar disorder-A guide for psychologists and clinically focused review.

Sleep problems are highly prevalent in bipolar disorder (BD) and constitute an important therapeutic focus in this population: They are highly impairing and distressing, are an area of subjective importance to consumers, and likely play a role in predicting/triggering mood episodes. The aim of this review is to orient psychologists and psychotherapists to current research relevant to their clinical practice with people with BD, including (a) the prevalence and presentation of sleep problems, (b) the impacts and correlates of impaired sleep, and (c) the relationship between sleep problems and mood symptoms (including the predictive/triggering role of sleep in BD mood relapses). Detailed recommendations for assessment and cognitive-behavioural intervention strategies for use in BD are described. It will be concluded that although some sleep problems and comorbidities require interdisciplinary collaboration, a range of evidence-informed strategies can be effectively and appropriately applied by clinical psychologists and psychotherapists.

A screening method for sleep disturbances at the end-of-life.

OBJECTIVE: To evaluate sleep disturbances and to verify the accuracy of three screening tests to detect them in patients at the end-of-life admitted in a hospital palliative care unit. METHOD: The level of sleep disturbances was evaluated through the Pittsburgh Sleep Quality Index (PSQI) in 150 palliative patients. This questionnaire was the criterion variable for testing the three screening tests used: Edmonton Symptom Assessment System (ESAS-Sleep subscale); the single question "How much do you worry about your sleep problems?" which is answered on a scale of 0-10 (Sleep-Worry-Q) and another single question: "Do you think you have sleep problems?" with two response categories, Yes/No (Sleep-Problem-Q). RESULTS: According to the PSQI (cut-off point: 8), 87% of patients presented sleep disturbances. The ESAS-Sleep (cut-off point: 3) showed a sensitivity of 0.87, a specificity of 0.58, and an AUC of 0.729; the Sleep-Worry-Q (cut-off point: 4) showed a sensitivity of 0.95, a specificity of 0.68, and an AUC of 0.854; the Sleep-Problem-Q obtained a sensitivity of 0.92 and a specificity of 0.65. SIGNIFICANCE OF RESULTS: Patients at the end-of-life, near the time of death, have high levels of sleep disturbances that can be detected early, with better diagnostic accuracy, with the Sleep-Worry-Q. Although from a clinical point of view, the application of the Sleep-Problem-Q may be more advantageous, as it presents good diagnostic accuracy, greater simplicity, and brevity.

[Circadian rhythm sleep disorders: clinical picture, diagnosis and treatment]. / Troubles du rythme circadien veille-sommeil†: tableau clinique, diagnostic et prise en charge.

Circadian rhythm sleep disorders (CRSD) represent sleep-wake disturbances due to a disruption of endogenous circadian system or to a desynchronization between internal sleep-wake rhythms and the external environment. They comprise seven diagnostic entities grouped in two main categories: endogenous and exogenous. The patients typically describe chronic excessive daytime sleepiness and/or insomnia symptoms, impacting their daytime functioning. The exact prevalence of CRSD is probably underestimated. The diagnosis is based on sleep diary coupled with actigraphy. Several therapeutic options are validated to allow the realignment between endogenous circadian rhythm and the external environment. The correct diagnostic of CRSD is important to improve the patient's quality of life and to propose them appropriate treatment.

Les troubles du rythme circadien veille-sommeil (TRCVS) résultent d'un dysfonctionnement du rythme circadien endogène ou d'une désynchronisation entre ce dernier et l'environnement extérieur. Ce groupe de pathologies du sommeil comprend 7 sous-entités réparties en 2 catégories : des troubles exogènes et des troubles endogènes. La symptomatologie commune sont des plaintes chroniques de somnolence diurne et/ou d'insomnie, ayant des répercussions sur le fonctionnement quotidien. Leur prévalence exacte est inconnue et les TRCVS sont potentiellement sous-diagnostiqués. Le diagnostic repose sur l'utilisation de l'agenda de sommeil et de l'actigraphie. Diverses approches thérapeutiques existent pour permettre une resynchronisation entre le rythme circadien endogène et l'environnement extérieur.

[Chinese expert consensus on the assessment and management of stroke-related sleep disorders].

Stroke-related sleep disorders (SSD) are common symptoms after stroke, which are common but easily ignored. Studies have shown that sleep disorders in stroke patients would have negative impact on prognosis. However, there is still a lack of consensus and guidance on SSD evaluation and management worldwide. This consensus proposes the concept of SSD based on systemic literature review and discussion with experts. It comprises recommendations of assessment and management for all types of SSD, including insomnia, excessive daytime sleepiness, sleep apnea, rapid eye movement (REM) sleep behavior disorder, restless leg syndrome/periodic limb movements of sleep, circadian rhythm sleep-wake disorders. The purpose of this consensus is to provide a standard reference of SSD management.

Insufficient sleep syndrome: An unrecognized but important clinical entity.

BACKGROUND: A sleep clinic for adults and children was established in the Tokyo Bay Urayasu Ichikawa Medical Centre, in August 2012. Given that few sleep clinics are available in Japan specifically for children, this clinic provides the opportunity to provide data on child patients with sleep problems. METHODS: Records of patients who visited the sleep clinic at the Tokyo Bay Urayasu Ichikawa Medical Centre aged ≤20 years at the first visit were retrospectively examined, along with the initial and final diagnoses. RESULTS: Of 2,157 patients who visited the sleep clinic at Tokyo Bay Urayasu Ichikawa Medical Centre between August 2012 and March 2017, 181 were ≤20 years old. In these 181 patients, the most frequent final diagnosis was insufficient sleep syndrome (ISS), n = 56, followed by circadian rhythm sleep-wake disorder, n = 28; insomnia, n = 28; and sleep-related movement disorder, n = 15. CONCLUSIONS: Insufficient sleep produces various brain dysfunctions in both adults and children, and is associated with behavioral, cognitive and physical problems, as well as with atypical early development. Insufficient sleep has also been reported to cause obesity. Insufficient sleep-induced obesity is often associated with the occurrence of metabolic syndrome. More effort is needed to ensure that children are receiving sufficient sleep.

The impact of shift work on intensive care nurses' lives outside work: A cross-sectional study.

AIMS AND OBJECTIVES: To examine how shift work affects intensive care nurses' lives outside work. BACKGROUND: Shift work is unavoidable for many nurses. When attempting to minimise negative effects of shift work, it is important to identify areas which affect nurses working shifts. DESIGN: A cross-sectional study. METHODS: A questionnaire survey among Danish intensive care nurses concerning experiences with shift work and family life, spare time activities, sleep and health. RESULTS: A total of 114 nurses (88%) participated. Shift work was found to influence the opportunities for spare time activities, and about 25% of both evening- and night-shift groups found that working shifts sometimes led to social isolation. A total of 58% of nurses working evening shifts sometimes to very often experienced having trouble falling asleep when working shifts. Night-shift workers had a higher percentage of physical and mental symptoms when working shifts compared with evening-shift workers, with mood swings and headaches being the most common. The median score for thriving on working shifts was 8 (IQR 5-9) for evening-shift workers and 8 (IQR 7-9) for night-shift workers (scale 0-10 with 10 being the highest level of thriving). CONCLUSION: Shift workers reported that working shifts had a negative impact on life outside work. Opportunities for participating in spare time activities and difficulties falling asleep after shifts were the main issues for evening-shift workers, whereas physical symptoms such as headaches and mood swings were more dominant among night-shift workers. Despite the negative effects, the participants generally thrived on working shifts. RELEVANCE TO CLINICAL PRACTICE: By identifying modifiable areas which negatively influence life outside work when working shifts, it will be possible subsequently to plan interventions aimed at decreasing the negative effects. Interventions may include nurses having increased influence on their work schedules and education in sleep hygiene and dietary habits.

Sleep-related problems in the US working population: prevalence and association with shiftwork status.

OBJECTIVE: To estimate the prevalence of a comprehensive set of self-reported sleep problems by job characteristics, including shiftwork status, among a representative sample of US workers. METHODS: Data for 6338 workers aged ≥18 years were obtained from the National Health and Nutrition Examination Survey. Short sleep duration was defined as <7 hours per weekday/workday. Sleep quality was categorised as good, moderate and poor based on the frequency of 6 sleep-related symptoms. A sleep-related activities of daily living (ADL) score ≥2 was defined as impaired. Insomnia was defined as having poor sleep quality and impaired ADL. Shiftwork status was categorised as daytime, night, evening, rotating or another schedule. Prevalence rates were calculated and multivariate logistic regression analyses were used. RESULTS: The prevalence of short sleep duration (37.6% overall) was highest among night shift workers (61.8%; p<0.001). The prevalence of poor sleep quality was 19.2% among all workers, with the highest prevalence among night shift workers (30.7%, p=0.004). The prevalence of impaired ADL score (24.8% overall) and insomnia (8.8% overall) was also highest for night shift workers (36.2%, p=0.001 and 18.5%, p=0.013, respectively). In multivariate analysis, night shift workers had the highest likelihood of these sleep problems. CONCLUSIONS: Self-reported short sleep duration, poor sleep quality, impaired ADL score and insomnia are common among US workers especially among night shift workers. Although these findings should be confirmed with objective sleep measures, they support the need for intervention programmes to improve sleep quantity and quality among night shift workers.

Clinical and polysomnographic characteristics of excessive daytime sleepiness in children.

PURPOSE: This study aimed to delineate the clinical and polysomnography (PSG) characteristics of sleep disorders in children with excessive daytime sleepiness (EDS). METHODS: Between February 2002 and June 2015, 622 pediatric patients with EDS were evaluated with overnight PSG and the Multiple Sleep Latency Test at the Samsung Medical Center. The medical records; questionnaire responses about depression, sleepiness, sleep habits; and sleep study data of 133 patients without obstructive sleep apnea (OSA) were reviewed retrospectively. RESULTS: The patients (63 girls, 70 boys) slept for an average of 7 h 30 min and 8 h 44 min on weekdays and weekends, respectively. The mean Epworth Sleepiness Scale score was 11.01 ± 4.09 and did not differ significantly among sleep disorders. Among the 102 patients who completed the depression questionnaire, 53 showed depressive feelings, which were moderate or severe in 39, with no significant differences among specific sleep disorders. Thirty-four patients exhibited normal PSG results. Seventeen of them were concluded as not having any sleep disorders, and the others as having delayed sleep phase disorder (DSPD). Narcolepsy (n = 78) was the most common disorder, followed by DSPD (n = 17) and idiopathic hypersomnia (n = 12). CONCLUSIONS: Pediatric patients with EDS had various sleep disorders and some did not have any sleep disorder despite EDS. More than half the patients with EDS showed depressive feelings affecting their daily lives. For pediatric patients with EDS, a systematic diagnostic approach including questionnaires for sleep habits and emotion and PSG is essential for accurate diagnosis and treatment.

Seasonal variations in sleep disorders of nurses.

AIMS AND OBJECTIVES: To investigate the difference between nurses and the general population regarding seasonal variations in sleep disorders during 2004-2008. The effects of season and group interaction on sleep disorders with regard to different comorbidities were also examined. BACKGROUND: Studies on seasonal variations in sleep disorders were mainly conducted in Norway for the general population. Furthermore, whether different comorbidities cause seasonal variations in sleep disorders in nurses remains unknown. DESIGN: A retrospective study. METHODS: Data from the Taiwan National Health Insurance Research Database were used in generalised estimating equation Poisson distribution models to investigate the differences in sleep disorders between nurses and the general population diagnosed with sleep disorders (each n = 7643) as well as the interaction effects of sleep disorders between the groups with respect to different seasons. Furthermore, the interaction effects between groups and seasons on sleep disorders in the subgroups of comorbid anxiety disorders and depressive disorders were studied. RESULTS: Both the nurses and the general population had fewer outpatient visits for sleep disorders in winter than in other seasons. The nurses had fewer outpatient visits for sleep disorders than the general population did in each season. The nurses had more outpatient visits for sleep disorders in winter than in summer compared with the general population in the comorbid depressive disorder subgroup but not in the comorbid anxiety disorder subgroup. CONCLUSIONS: Nurses and the general population exhibited similar seasonal patterns of sleep disorders, but nurses had fewer outpatient visits for sleep disorders than the general population did in each season. For nurses with comorbid depressive disorders, outpatient visits for sleep disorders were more numerous in winter than in summer, potentially because nurses with comorbid depressive disorders are affected by shorter daylight exposure during winter. RELEVANCE TO CLINICAL PRACTICE: Depression and daylight exposure may be considered in mitigating sleep disorders in nurses.

Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking.

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

Sleep-wake cycle phenotypes in young people with familial and non-familial mood disorders.

OBJECTIVES: Converging evidence identifies that the offspring of parents with bipolar disorder (BD), individuals at clinical high risk of BD, and young people with recent onset BD may differ from other clinical cases or healthy controls in terms of sleep-wake profiles. However, it is possible that these differences may reflect current mental state, subtype of mood disorder, or familial traits. This study aimed to determine objective and subjective sleep-wake profiles in individuals aged 15-25 years with a current major depressive episode, in relation to familial traits. METHODS: Frequency matching was employed to ensure that each individual with a confirmed family history of BD (FH+) could be compared to four controls who did not have a familial mood disorder (FH-). Pre-selected objective actigraphy and subjective Pittsburgh Sleep Quality Index (PSQI) ratings were compared using one-way analysis of variance (ANOVA) and applying the Benjamini-Hochberg (BH) correction for false discoveries. RESULTS: The sample comprised 60 individuals with a mean age of 19 years. The FH+ (n=12) and FH- groups (n=48) differed on three key sleep parameters: mean sleep duration on week nights (P=.049), variability in waking after sleep onset (P=.038), and daily disturbances (PSQI dimension of sleep disturbance and daytime dysfunction; P=.01). CONCLUSIONS: The sleep profiles we identified in this study, especially the daily disturbances phenotype, provide support for research into endophenotypes for BD. Also, the findings may offer the opportunity for more tailored, personalized interventions that target specific components of the sleep-wake cycle in individuals with a family history of BD.

Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder.

The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P < 0.001). These results indicate that home saliva sampling with objective measures of light exposure and sample timing, can assist in identifying accurate home DLMOs.