Sleep quality,chronotype and metabolic syndrome components in bipolar disorders during the remission period: Results from the FACE-BD cohort

Data on sleep or circadian abnormalities and metabolic disturbances in euthymic bipolar disorders are scarce and based on small sample sizes. The aim of this study was to explore the associations between sleep disturbances, chronotype and metabolic components in a large sample of euthymic patients with bipolar disorders (BD). From 2009 to 2015, 752 individuals with bipolar disorders from the FACE-BD cohort were included and assessed for sleep quality, chronotype and metabolic components. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to confirm the diagnosis of BD. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index and chronotype with the Composite Scale of Morningness. Sociodemographic and clinical characteristics, psychotropic treatment, psychiatric comorbidities and blood samples were collected. In our sample, 22.4% of individuals with BD presented with a metabolic syndrome, 53.7% had sleep disturbances, 25.4% were considered as having an evening chronotype and 12.6% as having a morning chronotype. Independently of potential confounders, euthymic patients with sleep disturbances had a higher abdominal circumference, and patients with evening chronotype had a significantly higher level of triglycerides. There was an association between evening chronotype and an increased atherogenic index of plasma (OR = 4.8, 95%CI = 1.6–14.7). Our findings contribute the scant literature on the relationship between sleep quality, chronotype and cardiometabolic components in euthymic individuals with BD and highlight the need to improve quality of sleep and patient education about healthier sleep-hygiene practices.     

A relationship between nightmare content and somatic stimuli in a sleep-disordered population: A preliminary study.

This study aimed to examine the influence of specific sleep disorders on dream content. The authors hypothesized that: (a) waking somatic concerns influence dream content and (b) somatic stimulation associated with specific sleep disorders influence dream content items. The subjects (N = 124) were included if they demonstrated obstructive sleep apnea, narcolepsy, an EEG arousal disorder during sleep, or periodic leg movements during sleep (PLMS), based on standard polysomnography. The 42-item Wahler Physical Symptom Inventory was used to quantify somatic concerns. Dream content and frequency was assessed with a 37-item Dream Questionnaire. Ten symptom-dream pairs were selected as mutually relevant and subjected to chi-square analysis. 84.6% of all subjects reported having bad dreams (N = 105). A significant proportion of patients who complain of excessive perspiration dream about perspiring, and significant proportions of those who report difficulty breathing while awake dream about feelings of choking and suffocation. Recurring dreams and dreams of paralysis are significantly more prominent in patients with narcolepsy. Patients with sleep apnea do not dream of choking/feelings of suffocation with greater frequency than nonapneics. These findings suggest that somatic stimulation associated with specific sleep disorders appears to have an inconsistent influence on certain dream content items. Furthermore, dream mentation appears to feature waking concerns, rather that being related to events associated with during sleep disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation among clock gene expression rhythms,sleep quality,and meal conditions in delayed sleep-wake phase disorder and night eating syndrome

Clock genes that comprise the circadian clock system control various physiological functions. Delayed sleep-wake phase disorder (DSWPD) and night eating syndrome (NES) are characterized by delayed sleep and meal timing, respectively. We estimated that clock gene expression rhythms in DSWPD patients may be delayed in comparison with the healthy subjects due to delayed melatonin secretion rhythms, producing eveningness chronotype in these individuals. However, it was difficult to estimate which clock gene expression rhythms were delayed or not in NES patients, because previous studies revealed that melatonin secretion rhythm was a little delayed compared with healthy individuals and that chronotype of NES patients depended on the individuals. Therefore, we examined expression rhythms of clock genes such as Period3 (Per3), nuclear receptor subfamily 1, group D, member 1 (Nr1d1) and Nr1d2 in these patients. Further, we expected sleep and meal patterns in DSWPD and NES patients may be more diverse than patterns observed in healthy subjects, and thus analyzed relationships among clock gene expression rhythms, sleep quality, sleep midpoint time, and meal times. We enrolled healthy male participants along with DSWPD and NES male patients, and asked all participants to answer questionnaires and to keep diaries to record information on their sleep and meals. Further, we asked them to collect 5–10 beard follicle samples, 6 times every 4 h. We measured clock gene expression rhythms using total RNA extracted from beard follicle cells. Peak time of clock gene expression in the NES group showed more diversity than the other groups, and that in the DSWPD group was delayed compared with the control group. In addition, the peak time of clock gene expression was negatively correlated with sleep quality and positively correlated with meal time after a long fast. Amplitudes of clock gene expression, especially Per3, positively responded to better mental and physical conditions as well as with better sleep quality. Results of this study suggest that peak times of clock gene expression in NES patients depended on the individuals; some patients with NES showed similar clock gene expression rhythm to healthy subjects, and other patients with NES showed similar to DSWPD patients. Moreover, this study suggests that meal time after a long fast may influence more determination in clock gene expression rhythms than the time of breakfast. Therefore, this study also indicates that Per3 clock gene may be one of the parameters that will help us understand sleep and meal rhythm disturbances.     

Bullying,sleep/wake patterns and subjective sleep disorders: Findings from a cross-sectional survey

The aim of this study was to explore: (a) sleep patterns and disorders possibly associated with adolescent bullying profiles (pure bully, pure victim, bully/victim and neutral) and (b) the effect of sleep on psychosocial problems (externalized and internalized) related to bullying. The sample consisted of 1422 students aged 10–18 (mean?=?14.3, SD?=?2.7; 57% male) from five socioeconomically diverse schools in France. Bullying profiles were obtained using the revised Bully–Victim Questionnaire. Subjective sleep disorders were assessed using the Athens Insomnia Scale. School-week and weekend sleep/wake patterns were recorded. Internalizing problems were investigated using a Perceived Social Disintegration Scale and a Psychological Distress Scale. Externalizing behaviors were assessed using a General Aggressiveness Scale and an Antisocial Behavior Scale. These questionnaires were administered during individual interviews at school. After controlling for effects of gender and age, victims of bullying showed significantly more subjective sleep disturbances than the pure-bully or neutral groups (p?<?0.001). Bullies’ sleep schedules were more irregular (p?<?0.001 for bedtime irregularity and p<0.01 for wake-up time irregularity) and their sleep duration was shorter than their schoolmates (p?<?0.001 for the school week and p?<?0.05 for the weekend). There was an effect of sleep on psychosocial problems related to bullying, and our results indicate that sleep has a moderating effect on aggression in bullies (p?<?0.001). This would suggest a higher vulnerability of bullies to sleep deprivation. These results show differences in sleep problems and patterns in school-bullying profiles. Findings of this study open up new perspectives for understanding and preventing bullying in schools, with implications for research and clinical applications.     

Clinical significance of social jetlag in patients with excessive daytime sleepiness

ABSTRACT

Social jetlag has recently attracted attention as the circadian misalignment between biological and social clocks. We aimed to examine social jetlag and its effect on daytime sleepiness and daily functions in patients with narcolepsy, behaviorally induced insufficient sleep syndrome (BIISS) and delayed sleep-wake phase disorder (DSPD). The levels of social jetlag (SJL_mid) and sleep-corrected social jetlag (SJL_sc) were calculated for each patient, and the effect of these social jetlag-related parameters on daytime sleepiness and daily functions were examined. Objective sleepiness measured by the mean sleep latency in the multiple sleep latency test, subjective sleepiness assessed by the Epworth sleepiness scale (ESS), health-related quality of life (HRQoL) assessed by the SF-8 health survey, and incidences of mistakes in daily activities, traffic accidents and near-miss events related to daytime sleepiness were compared among the narcolepsy (n = 39), BIISS (n = 87) and DSPD (n = 28) groups. Both SJL_mid and SJL_sc showed a negative correlation with physical HRQoL in patients with narcolepsy and a positive correlation with the ESS score in patients with DSPD. In patients with BIISS, SJL_sc reflected sleep loss rather than circadian misalignment; moreover, SJL_sc was not associated with daytime sleepiness and daily functions. Social jetlag was not associated with incidences of mistakes in daily activities, traffic accidents and near-miss events.

The state of social jetlag and its association with daily functions differed among the narcolepsy, BIISS and DSPD groups. Social jetlag represented sleep debt in BIISS, circadian misalignment in narcolepsy and both in DSPD. Our results thus show that the clinical manifestations and significance of social jetlag differ depending on the underlying sleep disorders.     

Melatonin ameliorates sleep–wake disturbances and autism-like behaviors in the Ctnnd2 knock out mouse model of autism spectrum disorders

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication, as well as restrictive and repetitive behaviors. In addition, patients with ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (CTNND2) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study demonstrated that the deletion of Ctnnd2 in mice led to autism-like behaviors. However, to our knowledge, no study has investigated the effects of Ctnnd2 deletion on sleep in mice. In this study, we investigated whether the knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep–wake disorders in mice and identified the effects of oral melatonin (MT) supplementation on Ctnnd2 KO mice. Our results demonstrated that the Ctnnd2 KO mice exhibited ASD-like behaviors and sleep–wake disorders that were partially attenuated by MT supplementation. Overall, our current study is the first to identify that knockdown of Ctnnd2 gene could induce sleep–wake disorders in mice and suggests that treatment of sleep–wake disturbances by MT may benefit to autism-like behaviors causing by Ctnnd2 gene deletion.     

A prospective study of delayed sleep phase syndrome in patients with severe resistant obsessive-compulsive disorder

There have been relatively few studies examining sleep in patients with obsessive-compulsive disorder (OCD) and these have produced contradictory findings. A recent retrospective study identified a possible association between OCD and a circadian rhythm sleep disorder known as delayed sleep phase syndrome (DSPS). Patients with this pattern of sleeping go to bed and get up much later than normal. They are unable to shift their sleep to an earlier time and, as a result, suffer considerable disruption to social and occupational functioning. In this study, we examined the sleep of patients with OCD prospectively. We aimed to establish the frequency of DSPS in this population and any associated clinical or demographic factors which might be implicated in its aetiology.     

Evening chronotype,late weekend sleep times and social jetlag as possible causes of sleep curtailment after maintaining perennial DST: ain’t they as black as they are painted?

ABSTRACT

People sleep less in response to setting social clocks earlier relative to the sun clocks. We proposed here a model-based approach for estimating sleep loss as the difference between weekend and weekday risetimes divided on the difference between weekend risetime and weekday bedtime. We compared this approach with a traditional approach to estimating sleep curtailment as the difference in weekly average sleep duration in two conditions. Weekday and weekend sleep times reported for 320 samples provided possibility of testing whether evening types with later weekend sleep times and larger social jetlag differ from morning types with earlier weekend sleep times and smaller social jetlag on amount of sleep lost (1) throughout the week and (2) in response to an advance of weekday wakeups, for instance, after the expected installation of perennial Daylight Saving Time (DST). We found that (1) an amount of sleep lost due to advancing shift of weekday wakeups depends upon neither chronotype nor weekend sleep times nor social jetlag, (2) a very large amount of sleep is usually lost by evening types with later weekend sleep times and larger social jetlag and (3) an essential sleep loss is caused by our usual work/school schedules, even in morning types with early weekend sleep times and small social jetlag. As compared to such permanent sleep losses experienced by any types, an additional loss due to switching from Standard Time (ST) to perennial DST are expected to be relatively small. We also found that the traditional way of calculation of sleep curtailment leads to paradoxical conclusions, such as (1) sleep loss is larger when social jetlag is smaller, not larger, (2) sleep loss is larger when weekend sleep times are earlier, not later, (3) despite 1-h difference between two student samples in weekday wakeups, their sleep losses can be identical.     

Melatonin Shifts Human Orcadian Rhythms According to a Phase-Response Curve

A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.     

Melatonin Shifts Human Orcadian Rhythms According to a Phase-Response Curve

A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.     

Ca2+‐Dependent Hyperpolarization Pathways in Sleep Homeostasis and Mental Disorders

Although we are beginning to understand the neuronal and biochemical nature of sleep regulation, questions remain about how sleep is homeostatically regulated. Beyond its importance in basic physiology, understanding sleep may also shed light on psychiatric and neurodevelopmental disorders. Recent genetic studies in mammals revealed several non‐secretory proteins that determine sleep duration. Interestingly, genes identified in these studies are closely related to psychiatric and neurodevelopmental disorders, suggesting that the sleep‐wake cycle shares some common mechanisms with these disorders. Here we review recent sleep studies, including reverse and forward genetic studies, from the perspectives of sleep duration and homeostasis. We then introduce a recent hypothesis for mammalian sleep in which the fast and slow Ca²⁺‐dependent hyperpolarization pathways are pivotal in generating the SWS firing pattern and regulating sleep homeostasis, respectively. Finally, we propose that these intracellular pathways are potential therapeutic targets for achieving depolarization/hyperpolarization (D/H) balance in psychiatric and neurodevelopmental disorders.     

Daytime sleepiness in the obese: not as simple as obstructive sleep apnea

Objective: Excessive daytime sleepiness is a common symptom in obese patients, but what drives this condition is unclear. The objective was to look for clinical, anthropometric, biochemical, and polysomnographic predictors of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in obese patients. Research Methods and Procedures: The ESS questionnaire was completed by 1055 consecutive patients presenting for obesity surgery. Those at high risk for obstructive sleep apnea (n = 331) had diagnostic overnight polysomnography preoperatively. All patients had preoperative clinical, hematologic, and biochemical measurements and completed multiple questionnaires. Results: There was no significant relationship between ESS score and any measure of diagnostic polysomnography factors, including total apnea hypopnea index. Subtle increases in ESS scores were reported in men, older patients, and those with type 2 diabetes. However, general demographic, anthropometric, and biochemical measures of the metabolic syndrome explained only 3% of ESS score variance, and inflammatory markers of C‐reactive protein and total white cell count were not predictive. Poor Short Form‐36 energy scores (b = ?0.18, p < 0.001) and high Beck Depression Inventory scores were predictive of higher ESS scores (b = 0.15, p < 0.001) and, along with increasing age and male gender, explained 10% of variance. Symptoms related to disturbed nocturnal sleep explained 30% of variance. Conclusion: In severely obese subjects, increased daytime sleepiness does not seem to be driven by obstructive sleep apnea, the degree of obesity, or anthropometric, metabolic, or inflammatory markers of the metabolic syndrome. It is, however, associated with poor energy, symptoms of depression, and symptoms of nocturnal sleep disturbance.     

Sleep and cancer: Synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries

Sleep and its impact on physiology and pathophysiology are researched at an accelerating pace and from many different angles. Experiments provide evidence for chronobiologically plausible links between chronodisruption and sleep and circadian rhythm disruption (SCRD), on the one hand, and the development of cancer, on the other. Epidemiological evidence from cancer incidence among some 1 500 000 study individuals in 13 countries regarding associations with sleep duration, napping or “poor sleep” is variable and inconclusive. Combined adjusted relative risks (meta-RRs) for female breast cancer, based on heterogeneous data, were 1.01 (95% CI: 0.97–1.06). Meta-RRs for cancers of the colorectum and of the lung in women and men and for prostate cancer were 1.08 (95% CI: 1.03–1.13), 1.11 (95% CI: 1.00–1.22) and 1.05 (95% CI: 0.83–1.33), respectively. The significantly increased meta-RRs for colorectal cancer, based on homogeneous data, warrant targeted study. However, the paramount epidemiological problem inhibiting valid conclusions about the associations between sleep and cancer is the probable misclassification of the exposures to facets of sleep over time. Regarding the inevitable conclusion that more research is needed to answer How are sleep and cancer linked in humans? we offer eight sets of recommendations for future studies which must take note of the complexity of multidirectional relationships.     

Shift work and sleep disorder comorbidity tend to go hand in hand

Taking into consideration that shift work has a wide-ranging impact on circadian and sleep functioning, it seems likely that shift work increases the risk of a general sleep disturbance, spread out over a multitude of comorbid sleep disorders. The aim of the present study is to analyze and present the sleep disorder data of 250 shift workers and 971 permanent day workers, taken from a nationally representative sample. Additional data concerning duration, timing, and quality of sleep, daytime functioning and social/family variables were added to the analyses. The results showed that the shift workers experienced significantly more difficulties with the variability of their sleep times, reported more napping and considered themselves more as poor sleepers than the day workers. Most importantly, shift work, in comparison with day work, appeared associated with a significantly higher prevalence of the clinical, International Classification of Sleep Disorders’ defined symptoms of nearly all main sleep disorders (including shift work disorder). For shift workers, the prevalence of a general sleep disturbance was 39.0% (95%CI 33.2 – 45.2), significantly higher than for day workers (24.6%, 95%CI 22.0 – 27.4). Moreover, shift workers were characterized by high levels of sleep disorder comorbidity. In addition, exclusively for shift workers, the prevalence of disordered sleep systematically decreased across decades of life and was considerably higher for single versus partnered shift workers. This study adds to the insight into the interacting factors that determine shift work coping and may play a role in occupational health interventions aimed at reducing sleep problems and thus improving the resilience and tolerance of the shift worker.     

Gamma-aminobutyric acid (GABA) receptor mediates suanzaorentang, a traditional Chinese herb remedy, -induced sleep alteration

Summary The sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are the most common treatments for insomnia. However, concerns regarding patterns of inappropriate use, dependence and adverse effects have led to caution in prescribing those sedative-hypnotic medications. On the other hand, a traditional Chinese herb remedy, suanzaorentang, has been efficiently and widely used in clinic for insomnia relief without severe side effects in Asia. Although suanzaorentang has been reported to improve sleep disruption in insomniac patients, its mechanism is still unclear. The present study was designed to elucidate the effects of oral administration of suanzaorentang on physiological sleep-wake architectures and its underlying mechanism in rats. We found that oral administration of suanzaorentang at the beginning of the dark onset dose-dependently increased non-rapid eye movement sleep (NREMS) during the dark period, but had no significant effect on rapid eye movement sleep (REMS). Our results also indicated that intracerebroventricular (ICV) administration of γ-aminobutyric acid (GABA) receptor type A antagonist, bicuculline, significantly blocked suanzaorentang-induced enhancement in NREMS during the dark period, but GABA_B receptor antagonist, 2-hydroxysaclofen had no effect. These results implicated that this traditional Chinese herb remedy, suanzaorentang increases spontaneous sleep activity and its effects may be mediated through the GABA_A receptors, but not GABA_B receptors.     

老年睡眠障碍患者胃管反流病、功能性肠病及功能性消化不良患病的现况调查分析

目的:调查老年睡眠障碍患者胃管反流病(GERD)、功能性肠病(FBD)及功能性消化不良(FD)的患病现况。方法:选择参加我院2012年春季体检人员中有睡眠障碍的患者为调查对象,进行"消化道症状问卷"调查,并按年龄分层进行比较。结果:共入选377例睡眠障碍患者,老年组确诊为GERD、FBD及FD患者129例(53.53%),发生率明显高于成年患者(45例,33.06%)(P0.01)。老年睡眠障碍患者中GERD和功能性便秘的发生率明显高于成年组,而FD及肠易激综合征患病的发生率均明显低于后者(P均0.01~0.05);老年睡眠障碍患者重叠型及GERD+FBD各亚型重叠发生率明显高于成年组,而单一型发生率明显低于后者(P均0.01~0.05)。结论:老年睡眠障碍患者GERD、FBD及FD的发生率均较成年人高,且以GERD及功能性便秘为主。     

Going beyond the limits: effect of clock disruption on human health

Abstract

Synchronisation of organisms’ physiology and behaviour with the external environment is necessary for survival and reproductive fitness. This is critical for human health also. In the past, humans were exposed to predictable natural day and night cycles that allowed the internal clock to synchronise the daily rhythms in physiology and behaviour with the external environment. However, the industrial revolution has made us a 24*7 society and forced the extension of day into night via adoption of artificial light in our lives. This has altered the perception of day and night and made it difficult for the biological processes to synchronise. Such weak synchronisation can be seen in different physiological and behavioural functions that are under circadian control, such as sleep–wake behaviour, melatonin and cortisol rhythms, core body temperature cycle, etc. This also influences the regulatory mechanism at cell and gene levels. Circadian disruption has resulted in increasing incidences of certain cancers, metabolic dysfunction and mood disorders. Several evidence suggest that exposure to aberrant light alters the brain functions that regulate emotion and mood. The present discussion focuses on understanding the effect of circadian disruption on human health, and its various aspects.     

Case study of circadian rhythm sleep disorder following haloperidol treatment: reversal by risperidone and melatonin

A patient with Gilles de la Tourette syndrome treated with haloperidol, ingested once daily after awakening from sleep, exhibited an irregular sleep-wake pattern with a free-running component of approximately 48 h. Transfer to risperidone, ingested once daily after awakening from sleep, was beneficial resulting in a sleep-wake cycle more synchronized at the appropriate phase to the external zeitgebers, and fewer nocturnal disturbances. The circadian sleep-wake schedule was fully synchronized when the patient had been subsequently treated with melatonin at 21:00h, before intended nocturnal sleep, in addition to risperidone in the morning. Restoration of the sleep-wake circadian pattern was accompanied by the patient's subjective report of significant improvement in his quality of life, social interactions, and occupational status. This observation suggests that circadian rhythm sleep disorders can be related to the typical neuroleptic haloperidol and restored by the atypical neuroleptic risperidone. Similar findings reported in patients suffering from other disorders support the hypothesis that the described disruption of the sleep-wake schedule is medication rather than illness-related. Therefore, it is very important to realize that circadian rhythm sleep disorders may be a side effect of neuroleptics.     

The involvement of serotonin receptors in suanzaorentang-induced sleep alteration

Summary Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in China, although its mechanism remains unclear. This study was designed to further elucidate the underlying mechanism of suanzaorentang on sleep regulation. One ingredient of suanzaorentang, zizyphi spinosi semen, exhibits binding affinity for serotonin (5-hydroxytryptamine, 5-HT) receptors, 5-HT_1A and 5-HT₂, and for GABA receptors. Our previous results have implicated that GABA_A receptors, but not GABA_B, mediate suanzaorentang-induced sleep alteration. In current study we further elucidated the involvement of serotonin. We found that high dose of suanzaorentang (4 g/kg/2 ml) significantly increased non-rapid eye movement sleep (NREMS) when comparing to that obtained after administering starch placebo, although placebo at dose of 4 g/kg also enhanced NREMS comparing with that obtained from baseline recording. Rapid eye movement sleep (REMS) was not altered. Administration of either 5-HT_1A antagonist (NAN-190), 5-HT₂ antagonist (ketanserin) or 5-HT₃ antagonist (3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile) blocked suanzaorentang-induced NREMS increase. These results implicate the hypnotic effect of suanzaorentang and its effects may be mediated through serotonergic activation, in addition to GABAergic system.