Network analysis of sleep bruxism in the EPISONO adult general population.

Sleep bruxism (SB) has been associated with biological and psychosocial factors. The assessment of SB includes self-report, clinical evaluation, and polysomnography. This study aimed to investigate the associations of self-reported SB with other sleep disorders and demographic, psychological, and lifestyle factors in the adult general population, and to investigate whether self-reported SB and polysomnographically (PSG) confirmed SB provide similar outcomes in terms of their associated factors. We recruited 915 adults from the general population in Sao Paulo, Brazil. All participants underwent a one-night PSG recording and answered questions about sex, age, BMI, insomnia, OSA risk, anxiety, depression, average caffeine consumption, smoking frequency, and alcohol consumption frequency. We investigated the link between SB and the other variables in univariate, multivariate, and network models, and we repeated each model once with self-reported SB and once with PSG-confirmed SB. Self-reported SB was only significantly associated with sex (p = 0.042), anxiety (p = 0.002), and depression (p = 0.03) in the univariate analysis, and was associated with insomnia in the univariate (p < 0.001) and multivariate (ß = 1.054, 95%CI 1.018-1.092, p = 0.003) analyses. Network analysis showed that self-reported SB had a direct positive edge to insomnia, while PSG-confirmed SB was not significantly associated with any of the other variables. Thus, sleep bruxism was positively associated with insomnia only when self-reported, while PSG-confirmed SB was not associated with any of the included factors.

Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.

Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

Effects of sleep deprivation on maternal behaviour in animal models: A systematic review and meta-analysis.

Pregnancy is a period of numerous physical and emotional changes in women's lives, including alterations in sleep patterns and worsening of pre-existing sleep disturbances, which possibly lead to impaired postpartum maternal behaviour and mother-infant relationship. The effects of sleep deprivation during pregnancy in maternal behaviour have been evaluated in preclinical studies, but have provided inconsistent results. Thus, in the present study, we aimed to evaluate the effects of sleep deprivation during pregnancy on maternal behaviour of animals through a systematic review and meta-analyses. After a two-step selection process, six articles were included, all of them describing rat studies. The most frequently used method of sleep deprivation was rapid eye movement sleep restriction, using the multiple-platform method. Four meta-analyses were performed, none of them presenting significant impact of sleep deprivation on maternal behaviour, failing to reproduce the results observed in previous clinical studies. In conclusion, our results show a lack of translational applicability of animal models to evaluate the effects of sleep deprivation during pregnancy on maternal behaviour.

Sleep deficit in COVID-19 health-care workers may increase the infection risk.

The COVID-19 pandemic has had negative effects on health-care workers. The rapid growth of the disease has led to overwhelmed health-care systems, overcrowded hospitals, an insufficient number of health-care professionals and shortages of medical equipment. The potential exposure of front-line health-care workers during the COVID-19 outbreak has led to self-isolation and the appearance of adverse feelings such as stress, anxiety and fear. All these factors, combined with an increased workload and extra and changed shifts, are determinants of a sleep-loss process that may result in insomnia. The exacerbated pro-inflammatory milieu caused by insomnia and sleep deprivation present in health professionals may therefore make them more prone to developing severe COVID-19 if infected and/or aggravate the symptoms of the disease. Keeping these professionals healthy and doing everything possible to prevent them from being infected with COVID-19 should be a top priority. As part of this effort, we must be aware of the important effects of insomnia on the immune systems of these professionals and take all possible measures to counter these effects.

Sleep quality of mother-caregivers of Duchenne muscular dystrophy patients.

BACKGROUND: Sleep disturbance is a common problem for caregivers. In general, patients with Duchenne muscular dystrophy (DMD) use noninvasive ventilation to maintain quality of life and improve survival. OBJECTIVE: The aim of this study was to evaluate the sleep quality of caregiver-mothers of sons with DMD and factors that are associated with their sleep quality. METHODS: We evaluated 32 caregiver-mothers of sons with DMD and 32 mothers of sons without any neuromuscular or chronic disease (control-CTRL group). The evaluation of quality of sleep was made using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Caregiver-mothers had poor sleep quality, specifically longer sleep latency and reduced sleep efficiency. The impaired sleep quality of the caregiver-mothers was associated with the length of time of noninvasive ventilation used by their sons. CONCLUSIONS: Our results suggest that caregiver-mothers of sons with DMD have poor quality of sleep, and the length of use of noninvasive ventilation of their sons is associated with better sleep of caregiver-mothers.

Sleep and quality of life in kidney transplant recipients with and without non-melanoma skin cancer: a comparative study.

Non-melanoma skin cancer (NMSC) is prevalent in kidney transplant recipients (KTR), related to the immunosuppressive effects of anti-rejection therapy. Sleep disturbances can alter the immune system and enhance oxidative stress, which may increase the risk of carcinogenesis. This study aimed to analyze the quality of life and sleep in KTR with and without NMSC. Participants answered a set of questionnaires, the WHOQOL-bref, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire and self-reported chronotype. The total sample was distributed in the following groups: KTR with NMSC (n = 42), KTR without NMSC (n = 43) and healthy controls (n = 41). The mean scores of the questionnaires were not statistically significant, except for 3 domains of PSQI (sleep quality, sleep latency and daily consequences of poor sleep). The KTR with NMSC and control group presented worse sleep quality. Worse sleep latency and more daytime consequences were found in KTR groups. All groups had a numerical predominance of low-quality sleep (PSQI) and greater sleepiness (EES). Higher risk of obstructive sleep apnea was not observed and the evening-type chronotype was most frequent. In the WHOQOL, compromised physical domain was observed in KTR. Significant results were reached in few aspects of quality of life and sleep comparing KTR and controls. All groups presented excessive daytime sleepiness and low-sleep quality.

Endocrine and Epigenetic Regulation as Common Pathways Underlying the Genetic Basis of Sleep Traits and Longevity.

The amount of sleep needed over one's lifespan is age dependent and not sleeping enough or sleeping in excess is associated with increased morbidity and mortality. Yet, the convergent molecular mechanisms that link longevity and sleep are largely unknown. We performed a gene enrichment study that (1) identified genes associated with both longevity and sleep traits and (2) determined molecular pathways enriched among these shared genes. We manually curated two sets of genes, one associated with longevity and aging and the other with sleep traits (e.g., insomnia, narcolepsy, sleep duration, chronotype, among others), with both gene lists heavily driven by hits from recent large-scale Genome-Wide Association Studies. There were 47 overlapping genes between the gene list associated with sleep traits (1064 genes total) and the genes associated with longevity (367 genes total), indicating significantly more overlap than expected by chance. An overrepresentation analysis identified enriched pathways that suggest endocrine and epigenetic regulation as potential shared mechanisms between sleep traits and longevity. Concordantly, functional network analysis retrieved two clusters, being one associated with proteins of nuclear functions and the other, with extracellular proteins. This overlapping gene set, and the highlighted biological pathways may serve as preliminary findings for new functional investigations of sleep and longevity shared genetic mechanisms.

Sleep, psychiatric and socioeconomic factors associated with substance use in a large population sample: A cross-sectional study.

Multiple elements modulate drug use, including sleep, which is increasingly being considered as an important contributor to substance use and abuse. The present study aimed to evaluate the association between sleep, psychiatric and socioeconomic/demographic factors and substance use in a large-scale representative sample from the city of São Paulo, Brazil. Data from the 2007 São Paulo Epidemiological Sleep Study (EPISONO) database were used. In the EPISONO study, volunteers underwent a polysomnographic exam and completed a series of questionnaires to assess objective and subjective sleep quality and associated comorbidities. Drug use was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Linear (univariate and multivariate) and logistic regressions were performed to identify factors associated with the use of the 4 most commonly used substances in the sample (tobacco, alcohol, cannabis and cocaine/crack). Structural equation models were used to establish theoretical networks to explain the relationship between sleep, psychiatric and socioeconomic factors and use of these substances. The logistic regression results showed that psychiatric symptoms, lower income, and poorer subjective sleep were the main factors associated with tobacco consumption; gender and occupational status with alcohol intake; age and occupation with cannabis use; and education with cocaine/crack use. The structural equation models partially supported these findings and identified significant effects of psychiatric symptoms on tobacco consumption, both directly and mediated by sleep. Our results reinforce previous findings concerning factors associated with generally misused substances and suggest that sleep should be considered as an important element in future substance use disorder studies.

Systematic review and meta-analysis of the behavioral effects of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

The spontaneously hypertensive rats (SHR) are the most widely used model for ADHD. While face and construct validity are consolidated, questions remain about the predictive validity of the SHR model. We aim at summarizing the evidence for the predictive validity of SHR by evaluating its ability to respond to methylphenidate (MPH), the most well documented treatment for ADHD. A systematic review was carried out to identify studies evaluating MPH effects on SHR behavior. Studies (n=36) were grouped into locomotion, attention, impulsivity or memory, and a meta-analysis was performed. Meta-regression, sensitivity, heterogeneity, and publication bias analyses were also conducted. MPH increased attentional and mnemonic performances in the SHR model and decreased impulsivity in a dose-dependent manner. However, MPH did not reduce hyperactivity in low and medium doses, while increased locomotor activity in high doses. Thus, since the paradoxical effect of stimulant in reducing hyperactivity was not observed in the SHR model, our study does not fully support the predictive validity of SHR, questioning their validity as an animal model for ADHD.

Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety-like behavior in mice.

OBJECTIVE: Sleep apnea has been associated with anxiety, but the mechanisms of the sleep apnea-anxiety relationship are unresolved. Sleep apnea causes oxidative stress, which might enhance anxiety-like behavior in rodents. To clarify the apnea-anxiety connection, we tested the effect of intermittent hypoxia, a model of sleep apnea, on the anxiety behavior of mice. METHODS: The rodents were exposed daily to 480 one-minute cycles of intermittent hypoxia to a nadir of 7±1% inspiratory oxygen fraction or to a sham procedure with room air. After 7 days, the mice from both groups were placed in an elevated plus maze and were video recorded for 10 min to allow analysis of latency, frequency, and duration in open and closed arms. Glyoxalase-1 (Glo1) and glutathione reductase-1 (GR1) were measured in the cerebral cortex, hippocampus, and striatum by Western blotting. RESULTS: Compared to controls, the intermittent hypoxia group displayed less anxiety-like behavior, perceived by a statistically significant increase in the number of entries and total time spent in open arms. A higher expression of GR1 in the cortex was also observed. CONCLUSION: The lack of a clear anxiety response as an outcome of intermittent hypoxia exposure suggests the existence of additional layers in the anxiety mechanism in sleep apnea, possibly represented by sleepiness and irreversible neuronal damage.

Effects of REM sleep restriction during pregnancy on rodent maternal behavior.

OBJECTIVE: To evaluate the effects of sleep restriction during pregnancy on maternal care and maternal aggression in a rodent model. METHODS: Twenty-three female Wistar rats were assigned to one of two groups: control (n=12) or sleep restriction (n=11) during the entire pregnancy. At the fifth postpartum day, the animals were subjected to the resident-intruder paradigm and to the pup retrieval test. RESULTS: Sleep restriction during pregnancy had no direct effects on maternal care. Regarding aggressive behavior, defensive aggression was increased by sleep loss, with a lower responsiveness threshold to hostile environmental stimuli. Sleep deprivation during gestation also reduced self-grooming behavior. CONCLUSION: Taking increased self-grooming as a behavioral correlate of anxiety in rodents, this study provides evidence that lactating dams were in a condition of reduced anxiety. From an adaptive perspective, this pattern of stress response may function to ensure proper maternal behavior, thereby guaranteeing the survival and viability of the litter. Under a translational perspective, the present article confronts the importance of biological and adaptive features to rodent maternal behavior with the relevance of sociocultural factors to the human mother-infant relationship and to the onset of postpartum depression.

Grooming analysis algorithm: use in the relationship between sleep deprivation and anxiety-like behavior.

Increased anxiety is a classic effect of sleep deprivation. However, results regarding sleep deprivation-induced anxiety-like behavior are contradictory in rodent models. The grooming analysis algorithm is a method developed to examine anxiety-like behavior and stress in rodents, based on grooming characteristics and microstructure. This study evaluated the applicability of the grooming analysis algorithm to distinguish sleep-deprived and control rats in comparison to traditional grooming analysis. Forty-six animals were distributed into three groups: control (n=22), paradoxical sleep-deprived (96 h, n=10) and total sleep deprived (6 h, n=14). Immediately after the sleep deprivation protocol, grooming was evaluated using both the grooming analysis algorithm and traditional measures (grooming latency, frequency and duration). Results showed that both paradoxical sleep-deprived and total sleep-deprived groups displayed grooming in a fragmented framework when compared to control animals. Variables from the grooming analysis algorithm were successful in distinguishing sleep-deprived and normal sleep animals regarding anxiety-like behavior. The grooming analysis algorithm and traditional measures were strongly correlated. In conclusion, the grooming analysis algorithm is a reliable method to assess the relationship between anxiety-like behavior and sleep deprivation.

Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety-like behavior in mice

Objective: Sleep apnea has been associated with anxiety, but the mechanisms of the sleep apnea-anxiety relationship are unresolved. Sleep apnea causes oxidative stress, which might enhance anxiety-like behavior in rodents. To clarify the apnea-anxiety connection, we tested the effect of intermittent hypoxia, a model of sleep apnea, on the anxiety behavior of mice. Methods: The rodents were exposed daily to 480 one-minute cycles of intermittent hypoxia to a nadir of 7±1% inspiratory oxygen fraction or to a sham procedure with room air. After 7 days, the mice from both groups were placed in an elevated plus maze and were video recorded for 10 min to allow analysis of latency, frequency, and duration in open and closed arms. Glyoxalase-1 (Glo1) and glutathione reductase-1 (GR1) were measured in the cerebral cortex, hippocampus, and striatum by Western blotting. Results: Compared to controls, the intermittent hypoxia group displayed less anxiety-like behavior, perceived by a statistically significant increase in the number of entries and total time spent in open arms. A higher expression of GR1 in the cortex was also observed. Conclusion: The lack of a clear anxiety response as an outcome of intermittent hypoxia exposure suggests the existence of additional layers in the anxiety mechanism in sleep apnea, possibly represented by sleepiness and irreversible neuronal damage.

Effects of REM sleep restriction during pregnancy on rodent maternal behavior

Objective: To evaluate the effects of sleep restriction during pregnancy on maternal care and maternal aggression in a rodent model. Methods: Twenty-three female Wistar rats were assigned to one of two groups: control (n=12) or sleep restriction (n=11) during the entire pregnancy. At the fifth postpartum day, the animals were subjected to the resident-intruder paradigm and to the pup retrieval test. Results: Sleep restriction during pregnancy had no direct effects on maternal care. Regarding aggressive behavior, defensive aggression was increased by sleep loss, with a lower responsiveness threshold to hostile environmental stimuli. Sleep deprivation during gestation also reduced self-grooming behavior. Conclusion: Taking increased self-grooming as a behavioral correlate of anxiety in rodents, this study provides evidence that lactating dams were in a condition of reduced anxiety. From an adaptive perspective, this pattern of stress response may function to ensure proper maternal behavior, thereby guaranteeing the survival and viability of the litter. Under a translational perspective, the present article confronts the importance of biological and adaptive features to rodent maternal behavior with the relevance of sociocultural factors to the human mother-infant relationship and to the onset of postpartum depression.