Clocks & Sleep, Volume 5, Issue 4 (December 2023) – 15 articles

The purpose of this paper is to investigate the impact of circadian lighting-induced melatonin suppression on patients with psychiatric and neurological disorders in hospital wards by using an ad-hoc metrology framework and the subsequent metrics formalized by the CIE in 2018. A measurement scheme was conducted in hospital ward rooms in the Department of Neurology, Zealand University Hospital, at Roskilde in Denmark, to evaluate the photometric and colorimetric characteristics of the lighting system, as well as its influence on the circadian rhythm of the occupants. The measurement scheme included point measurements and data logging, using a spectrophotometer mounted on a tripod with adjustable height to assess the newly installed circadian lighting system. The measured spectra were uploaded to the Luox platform to calculate illuminance, CCT, MEDI, etc., in accordance with the CIE S026 standard. Furthermore, the MLIT based on MEDI data logging results was calculated. In addition to CIE S026, we have investigated the usefulness of melatonin suppression models for the assessment of circadian performance regarding measured light. From the results, the lighting conditions in the patient room for both minimal and abundant daylight access were evaluated and compared; we found that access to daylight is essential for both illumination and circadian entrainment. It can be concluded that the measurement scheme, together with the use of the Luox platform and Canva template, is suitable for the accurate and satisfactory measurement of integrative lighting that aligns with CIE requirements and recommendations. Full article

Rapid eye movements (REM) sleep density is the parameter proposed to explain the variability in the amount of eye movements during REM sleep. Alterations in REM sleep density have been proposed as a screening criterion for individuals with depression and other mental health conditions, but its accuracy has not been properly evaluated. The lack of consensus and the variability of the methods used to score it reduces the external validity of the results, hindering an adequate analysis of its diagnostic accuracy and clinical applicability. This scoping review aimed to identify and quantify the methods used to score REM sleep density, describing their main characteristics. A literature search was conducted in PubMed, Scopus, PsycInfo, and Web of Science. Only studies with objective measures for REM sleep density analysis in individuals with depression were considered eligible. The final sample comprised 57 articles, covering 64 analyses of REM sleep density. The relative frequency methods were the predominant measurement parameter for analyzing REM sleep density across studies. The most frequently adopted REM estimation unit was the number of REM events followed by mini-epochs containing REM. The most common unit of measurement were frequency/time measures. The results demonstrate that there is no consistency in the methods used to calculate REM sleep density in the literature, and a high percentage of studies do not describe their methods in sufficient detail. The most used method was the number of REM episodes per minute of REM sleep, but its use is neither unanimous nor consensual. The methodological inconsistencies and omissions among studies limit the replicability, comparability, and clinical applicability of REM sleep density. Future guidelines should discuss and include a specific methodology for the scoring of REM sleep density, so it can be consensually implemented in clinical services and research. Full article

The gut microbiota (GM) plays a crucial role in human health. The bidirectional interaction between GM and the central nervous system may occur via the microbiota–gut–brain axis, possibly regulating the sleep/wake cycle. Recent reports highlight associations between intestinal dysbiosis and sleep disorders, suggesting that probiotics could ameliorate this condition. However, data are poor and inconsistent. The aim of this quantitative metanalytic study is to assess the GM composition in sleep disturbances and evaluate probiotics’ effectiveness for managing sleep disorders. A systematic review was carried out until July 2022 in online databases, limiting the literature research to human studies and English language articles. No significant GM diversity between patients with sleep disturbances versus healthy controls was found, revealed by α-diversity, while β-diversity is missing due to lack of proper reporting. However, probiotics supplementation significantly reduced the self-assessed parameter of sleep quality and disturbances Pittsburgh Sleep Quality Index (PSQI) score compared with the placebo. No difference in the Epworth Sleepiness Scale (ESS) score was found. While available data suggest that GM diversity is not related to sleep disturbances, probiotics administration strongly improves sleep quality as a subjective perception. However, heterogeneity of data reporting in the scientific literature should be considered as a limitation. Full article

Objective: To evaluate sleep disorders and associated factors in patients with rheumatoid-arthritis-associated interstitial lung disease (RA-ILD). Methods: We performed an observational study of 35 patients with RA-ILD (cases) and 35 age- and sex-matched RA patients without ILD (controls). We evaluated sleep disorders (Oviedo Sleep Questionnaire), positive psychological factors (resilience using the Wagnild and Young Resilience Scale, emotional intelligence using the 24-item Trait Meta-Mood Scale), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (36-item short-form survey), and fatigue (Functional Assessment of Chronic Illness Therapy Questionnaire). Other variables studied included the Charlson Comorbidity Index (CCI) and RA activity according to the DAS28-ESR. Results: Compared to the controls, the cases were characterized by poorer sleep quality with a higher prevalence of insomnia (42% vs. 20%; p = 0.039), greater severity of insomnia (p = 0.001), and lower sleep satisfaction (p = 0.033). They also had poorer resilience and emotional recovery and more severe anxiety and depression. A diagnosis of ILD was the only factor independently associated with the three dimensions of sleep quality. The predictors of poorer sleep satisfaction in patients with RA-ILD were age (β = −0.379), DAS28-ESR (β = −0.331), and usual interstitial pneumonia pattern (β = −0.438). The predictors of insomnia were DAS28-ESR (β = 0.294), resilience (β = −0.352), and CCI (β = 0.377). Conclusions: RA-ILD is associated with significant sleep disorders. RA-ILD seems to be an independent risk factor for sleep alterations, with a greater impact on insomnia. Age, disease activity, and comorbidity also play a role in sleep disorders in patients with RA-ILD. Full article

People with a diagnosis of schizophrenia often have poor sleep, even when their psychotic symptoms are relatively well managed. This includes insomnia, sleep apnoea, hypersomnia, and irregular or non-24 h sleep–wake timing. Improving sleep would better support recovery, yet few evidence-based sleep treatments are offered to this group. This paper presents a mixed methods feasibility and acceptability study of Light–Dark and Activity Rhythm Therapy (L-DART). L-DART is delivered by an occupational therapist over 12 weeks. It is highly personalisable to sleep phenotypes and circumstances. Ten participants with schizophrenia spectrum diagnoses and sleep problems received L-DART; their sleep problems and therapy goals were diverse. We measured recruitment, attrition, session attendance, and adverse effects, and qualitatively explored acceptability, engagement, component delivery, adherence, activity patterns, dynamic light exposure, self-reported sleep, wellbeing, and functioning. Recruitment was ahead of target, there was no attrition, and all participants received the minimum ‘dose’ of sessions. Acceptability assessed via qualitative reports and satisfaction ratings was good. Adherence to individual intervention components varied, despite high participant motivation. All made some potentially helpful behaviour changes. Positive sleep and functioning outcomes were reported qualitatively as well as in outcome measures. The findings above support testing the intervention in a larger randomised trial ISRCTN11998005. Full article

Background: The gold standard for diagnosing sleep bruxism (SB) and obstructive sleep apnea (OSA) is polysomnography (PSG). However, a final hypermotor muscle activity often occurs after apnea episodes, which can confuse the diagnosis of SB when using portable electromyography (EMG) devices. This study aimed to compare the number of SB episodes obtained from PSG with manual analysis by a sleep expert, and from a manual and automatic analysis of an EMG and electrocardiography (EKG) device, in a population with suspected OSA. Methods: Twenty-two subjects underwent a polysomnographic study with simultaneous recording with the EMG-EKG device. SB episodes and SB index measured with both tools and analyzed manually and automatically were compared. Masticatory muscle activity was scored according to published criteria. Patients were segmented by severity of OSA (mild, moderate, severe) following the American Academy of Sleep Medicine (AASM) criteria. ANOVA and the Bland–Altman plot were used to quantify the agreement between both methods. The concordance was calculated through the intraclass correlation coefficient (ICC). Results: On average, the total events of SB per night in the PSG study were (8.41 ± 0.85), lower than the one obtained with EMG-EKG manual (14.64 ± 0.76) and automatic (22.68 ± 16.02) analysis. The mean number of SB episodes decreases from the non-OSA group to the OSA group with both PSG (5.93 ± 8.64) and EMG-EKG analyses (automatic = 22.47 ± 18.07, manual = 13.93 ± 11.08). However, this decrease was minor in proportion compared to the automatic EMG-EKG analysis mode (from 23.14 to 22.47). The ICC based on the number of SB episodes in the segmented sample by severity degree of OSA along the three tools shows a moderate correlation in the non-OSA (0.61) and mild OSA (0.53) groups. However, it is poorly correlated in the moderate (0.24) and severe (0.23) OSA groups: the EMG-EKG automatic analysis measures 14.27 units more than PSG. The results of the manual EMG-EKG analysis improved this correlation but are not good enough. Conclusions: The results obtained in the PSG manual analysis and those obtained by the EMG-EKG device with automatic and manual analysis for the diagnosis of SB are acceptable but only in patients without OSA or with mild OSA. In patients with moderate or severe OSA, SB diagnosis with portable electromyography devices can be confused due to apneas, and further study is needed to investigate this. Full article

Explaining the complex structure and dynamics of sleep, which consist of alternating and physiologically distinct nonREM and REM sleep episodes, has posed a significant challenge. In this study, we demonstrate that a single wave model concept captures the distinctly different overnight dynamics of the four primary sleep measures—the duration and intensity of nonREM and REM sleep episodes—with high quantitative precision for both regular and extended sleep. The model also accurately predicts how these polysomnographic measures respond to sleep deprivation or abundance. Furthermore, the model passes the ultimate test, as its prediction leads to a novel experimental finding—an invariant relationship between the duration of nonREM episodes and the intensity of REM episodes, the product of which remains constant over consecutive sleep cycles. These results suggest a functional unity between nonREM and REM sleep, establishing a comprehensive and quantitative framework for understanding normal sleep and sleep disorders. Full article

Liver functions are regulated by the circadian rhythm; however, whether a weakened circadian rhythm is associated with impaired liver function is unclear. This study aims to investigate the association of characteristics of rest–activity rhythms with abnormal levels of biomarkers of liver function. Data were obtained from the National Health and Nutrition Examination Survey 2011–2014. Seven rest–activity rhythm parameters were derived from 24 h actigraphy data using the extended cosine model and non-parametric methods. Multiple logistic regression and multiple linear regression models were used to assess the associations between rest–activity rhythm parameters and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transaminase (GGT), albumin and bilirubin. Weakened overall rhythmicity characterized by a lower F statistic was associated with higher odds of abnormally elevated ALP (OR_Q1vs.Q5: 2.16; 95% CI 1.19, 3.90) and GGT (OR_Q1vs.Q5: 2.04; 95% CI 1.30, 3.20) and abnormally lowered albumin (OR_Q1vs.Q5: 5.15; 95% CI 2.14, 12.38). Similar results were found for a lower amplitude, amplitude:mesor ratio, interdaily stability and intradaily variability. Results were robust to the adjustment of confounders and cannot be fully explained by individual rest–activity behaviors, including sleep and physical activity. Weakened rest–activity rhythms were associated with worse liver function as measured by multiple biomarkers, supporting a potential role of circadian rhythms in liver health. Full article

It is well known that variations in light exposure during the day affect light sensitivity in the evening. More daylight reduces sensitivity, and less daylight increases it. On average days, we spend less time outdoors in winter and receive far less light than in summer. Therefore, it could be relevant when collecting research data on the non-image forming (NIF) effects of light on circadian rhythms and sleep. In fact, studies conducted only in winter may result in more pronounced NIF effects than in summer. Here, we systematically collected information on the extent to which studies on the NIF effects of evening light include information on season and/or light history. We found that more studies were conducted in winter than in summer and that reporting when a study was conducted or measuring individual light history is not currently a standard in sleep and circadian research. In addition, we sought to evaluate seasonal variations in a previously published dataset of 72 participants investigating circadian and sleep effects of evening light exposure in a laboratory protocol where daytime light history was not controlled. In this study, we selectively modulated melanopic irradiance at four different light levels (<90 lx). Here, we aimed to retrospectively evaluate seasonal variations in the responsiveness of the melanopsin system by combining all data sets in an exploratory manner. Our analyses suggest that light sensitivity is indeed reduced in summer compared to winter. Thus, to increase the reproducibility of NIF effects on sleep and circadian measures, we recommend an assessment of the light history and encourage standardization of reporting guidelines on the seasonal distribution of measurements. Full article

The circadian clock regulates a variety of biological processes that are normally synchronized with the solar day. Disruption of circadian rhythms is associated with health problems. Understanding the signaling mechanisms that couple cell physiology and metabolism to circadian timekeeping will help to develop novel therapeutic strategies. The integrated stress response (ISR) is activated by the cellular stressors to maintain physiological homeostasis by orchestrating mRNA translation. Aberrant ISR has been found in a number of neurological diseases that exhibit disrupted circadian rhythms and sleep. Recent work has started to uncover a critical role for the ISR in regulating the physiology of the circadian clock. Guanabenz (2,6-dichlorobenzylidene aminoguanidine acetate) is an orally bioavailable α2-adrenergic receptor agonist that has been used as an antihypertensive for decades. Recent studies demonstrated that guanabenz can regulate the ISR. Here, we assessed the effects of guanabenz on cellular and behavioral circadian rhythms using a multidisciplinary approach. We found that guanabenz can induce the ISR by increasing eIF2α phosphorylation in cultured fibroblasts as well as in the mouse brain. The hyperphosphorylation of eIF2α by guanabenz is associated with the shortened circadian period in cells and animals and the disruption of behavioral circadian rhythms in mice. Guanabenz administration disrupted circadian oscillations of the clock protein Per1 and Per2 in the mouse suprachiasmatic nucleus, the master pacemaker. These results uncover a significant yet previously unidentified role of guanabenz in regulating circadian rhythms and indicate that exacerbated ISR activation can impair the functions of the brain’s circadian clock by disrupting clock gene expression. Full article

The relationship between depression and insomnia is bidirectional and both conditions need to be treated adequately, especially in a vulnerable neurodevelopmental stage of adolescence. This study aimed to evaluate the effects of antidepressant treatment using vortioxetine (VOR) on the sleep architecture of depressed adolescents by using video-polysomnography (v-PSG), which has not been researched before. The v-PSG was performed on 30 adolescent in-patients (mean age of 15.0 years ± 1.5 SD, 21 girls) treated with VOR (dosage of 10/15/20 mg/day) administered orally once a day, before and after VOR treatment. The evaluated parameters were conventional sleep parameters, sleep fragmentation parameters, and selected spectral power indices. Symptoms of depression and insomnia before and after the treatment period were evaluated using valid and reliable questionnaires (the Children´s Depression Inventory and the Athens Insomnia Scale). Depressed adolescents showed higher REM latency and decreased REM sleep percentage after treatment than before the treatment period (p = 0.005, p = 0.009, respectively). Our study revealed REM suppression (increased REM latency and reduced REM sleep percentage), indicating altered sleep architecture as a potential result of VOR treatment, which seems to be dose-dependent. Full article

Humans have a circadian rhythm for which the period varies among individuals. In the present study, we investigated the amount of natural phase delay of circadian rhythms after spending a day under dim light (Day 1 to Day 2) and the amount of phase advance due to light exposure (8000 lx, 4100 K) the following morning (Day 2 to Day 3). The relationships of the phase shifts with the circadian phase, chronotype and sleep habits were also investigated. Dim light melatonin onset (DLMO) was investigated as a circadian phase marker on each day. In the 27 individuals used for the analysis, DLMO was delayed significantly (−0.24 ± 0.33 h, p < 0.01) from Day 1 to Day 2 and DLMO was advanced significantly (0.18 ± 0.36 h, p < 0.05) from Day 2 to Day 3. There was a significant correlation between phase shifts, with subjects who had a greater phase delay in the dim environment having a greater phase advance by light exposure (r = −0.43, p < 0.05). However, no significant correlations with circadian phase, chronotype or sleep habits were found. These phase shifts may reflect the stability of the phase, but do not account for an individual’s chronotype-related indicators. Full article

Social jetlag is associated with physical and mental health problems. With the increased popularity of telework, we investigated a specific form of social jetlag that we termed “telework jetlag”. This study aimed to clarify the relationship between telework jetlag—the difference in sleep and wake-up times between in-office and telework days—and mental health problems among Japanese hybrid workers. A cross-sectional study was conducted with 1789 participants from October to December 2021 using an online-based questionnaire. Telework jetlag, defined as the difference in the midsleep point between in-office and telework days, was investigated using two groups according to telework jetlag—those lagging <1 h versus ≥1 h. We used the six-item Kessler Scale as a nonspecific psychological distress scale for the outcome. Telework jetlag was significantly associated with psychological distress, and the ≥1 h group had a higher risk (odds ratio: 1.80) of developing high psychological distress (HPD) than the <1 h group in the multivariate analysis. Since most teleworkers are forced to have a hybrid work style that mixes going to work and teleworking, telework jetlag must be addressed to maintain the health of teleworkers. Full article

There is an urgent need for easily accessible treatment options for sleep problems to reduce the current treatment gap in receiving cognitive behavioral therapy for insomnia (CBT-I). Using a randomized controlled trial, we evaluated the efficacy of a CBT-I-based online program on sleep. Fifty-three volunteers (21–71 years; M_Age = 44.6 ± 12.5; 27 female) suffering from impaired sleep were randomly allocated either to the experimental group (EG, n = 27) or to an active control group (CG, n = 26). The EG participated in a 6-week CBT-I-based online program, while the CG received psychoeducation and sleep hygiene instructions. Sleep was assessed both objectively via ambulatory polysomnography (PSG) as well as subjectively via questionnaires at three time points (baseline, pre- and post-intervention). A one-month follow-up assessment was performed using questionnaires. The EG showed small but reliable improvements from pre- to post-intervention in PSG-derived wake after sleep onset (from 58.6 min to 42.5 min; p < 0.05) and sleep efficiency (from 86.0% to 89.2%; p < 0.05). Furthermore, subjective sleep quality (assessed via Pittsburgh Sleep Quality Index) improved significantly during intervention (p = 0.011) and follow-up (p = 0.015) in the EG alone. The Insomnia Severity Index decreased from pre- to post-intervention in both groups (EG: p = 0.003, CG: p = 0.008), while it further improved during follow-up (p = 0.035) in the EG alone. We show that a CBT-I-based online program can improve sleep not only subjectively but also objectively and can be a viable alternative when face-to-face interventions are not available. Full article

There seems to be a consensus that adolescents worldwide are not getting enough sleep. This study aimed to evaluate the psychometric properties of the Epworth Sleepiness Scale (ESS) in adolescents using the item response theory. A psychometric study was conducted with 2206 adolescents aged 18 and 19 years in the city of São Luís, Maranhão, Brazil. The dimensionality of the ESS was assessed by principal component analysis. A Samejima’s graded response model (SGRM) was fitted to it. The findings of this study showed a good internal consistency and the unidimensionality of the ESS. Considering the latent trait continuum, we obtained three levels, with anchor items. For the item ‘Sitting still in a public place’, the adolescents presented a small possibility of dozing in level 1, and a medium and great possibility in level 2. The item ‘Sitting around talking to someone’ presented small, medium, and great possibilities of dozing in level 3. The ESS with five items showed satisfactory psychometric properties. In addition, the results from the SGRM showed that adolescents with high levels of sleepiness are likely to nod off or sleep sitting up while talking to someone. This study allows us to understand excessive daytime sleepiness in adolescents. Full article