The interplay between X-chromosome functional dosage and circadian regulation in females.

PURPOSE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes. METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus. RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation. CONCLUSION: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

BACKGROUND: Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. METHODS: Involving 1042 volunteers aged 20 to 80 years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. RESULTS: Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] ß = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10 µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10 µmol/L. CONCLUSIONS: In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

Shared genetic mechanisms underlying association between sleep disturbances and depressive symptoms.

OBJECTIVES: Polygenic scores (PGS) for sleep disturbances and depressive symptoms in an epidemiological cohort were contrasted. The overlap between genes assigned to variants that compose the PGS predictions was tested to explore the shared genetic bases of sleep problems and depressive symptoms. METHODS: PGS analysis was performed on the São Paulo Epidemiologic Sleep Study (EPISONO, N = 1042), an adult epidemiological sample. A genome wide association study (GWAS) for depression grounded the PGS calculations for Beck Depression Index (BDI), while insomnia GWAS based the PGS for Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI). Pearson's correlation was applied to contrast PGS and clinical scores. Fisher's Exact and Benjamin-Hochberg tests were used to verify the overlaps between PGS-associated genes and the pathways enriched among their intersections. RESULTS: All PGS models were significant when individuals were divided as cases or controls according to BDI (R2 = 1.2%, p = 0.00026), PSQI (R2 = 3.3%, p = 0.007) and ISI (R2 = 3.4%, p = 0.021) scales. When clinical scales were used as continuous variables, the PGS models for BDI (R2 = 1.5%, p = 0.0004) and PSQI scores (R2 = 3.3%, p = 0.0057) reached statistical significance. PSQI and BDI scores were correlated, and the same observation was applied to their PGS. Genes assigned to variants that compose the best-fit PGS predictions for sleep quality and depressive symptoms were significantly overlapped. Pathways enriched among the intersect genes are related to synapse function. CONCLUSIONS: The genetic bases of sleep quality and depressive symptoms are correlated; their implicated genes are significantly overlapped and converge on neural pathways. This data suggests that sleep complaints accompanying depressive symptoms are not secondary issues, but part of the core mental illness.

Leptin moderates the relationship between sleep quality and memory function: A population-based study.

Sleep is crucial for memory, as it promotes its encoding, consolidation, storage, and retrieval. Sleep periods following learning enhance memory consolidation. Leptin, a hormone that regulates appetite and energy balance, also influences memory and neuroplasticity. It plays a neurotrophic role in the hippocampus, enhancing synaptic function and promoting memory processes. Given these associations between sleep, memory, and leptin, this study aimed to evaluate the interplay between sleep quality, memory complaints and leptin levels. Using data from the São Paulo Epidemiologic Sleep Study (EPISONO) 2007 edition, we analyzed data from 881 participants who underwent evaluations for subjective sleep quality (Pittsburgh Sleep Quality Index), memory function (Prospective and Retrospective Memory Questionnaire), body mass index and plasmatic leptin levels. After confirming that subjects with poor sleep quality had more memory complaints in our cohort, we observed that leptin levels were increased in individuals with more memory complaints, but there was no association between leptin levels and sleep quality. Mediation analysis reinforced the direct effect of sleep quality on memory function, but leptin had no indirect effect as mediator over the sleep-memory association. Moderation analysis revealed that leptin acted as a moderator in the relationship between sleep quality and memory, with increased leptin levels enhancing the effect of sleep quality over memory function. These findings underscore the intricate interplay between sleep, memory, and metabolic factors like leptin, shedding light on potential mechanisms through which sleep influences memory and cognitive functions. Further research is needed to elucidate the exact mechanisms underlying these relationships and their implications for overall health and well-being.

The relationship between sleep- and circadian rhythm-related parameters with dietary practices and food intake of sedentary adults: a cross-sectional study.

We aimed to explore the link between sleep-related parameters and dietary practices. This cross-sectional exploratory study includes sedentary individuals between 20 and 59 years of age. We applied exigent inclusion and exclusion criteria, such as weight stability and without humor- or sleep-related diseases. Also, shift workers were not included. We evaluated sleep quality (by Pittsburg Sleep Quality Index; PSQI), sleepiness (by Epworth Sleepiness Scale), chronotype (by Morningness Eveningness Questionnaire; MEQ), and social jetlag from sleep dairy. Moreover, Food Practices Measurement Scale was used to assess dietary practices. Food intake estimates (i. e., energy, eating window, and late-night dinner eating) were derived from two 24-h food recalls (R24h). For analysis, dietary practices and energy intake from R24h were considered dependent variables, while PSQI, ESS, MEQ, STJ, EW, and LNDE were considered independent variables. Our sample comprises 42 adults (21 women and 21 men; 35.4 (12.5) y; 25.6 (5.21) kg/m2 BMI; 26.5 (7.97) % body fat). We verified that persons with poor sleep quality showed lower dietary practice scores (MD - 6.68; p = 0.021). Besides, in regression analysis, chronotype (ß = 0.266; p = 0.039) was positively associated with dietary practices, and eating window was positively associated with energy intake (ß = 267 kcal; p = 0.023). In contrast to our hypothesis, other sleep- and circadian-related variables were not associated with dietary practices or energy intake. In summary, we conclude that morning chronotype appears to be related to better dietary practices from the Food Guide for the Brazilian Population guide and that higher eating window was positively associated with energy intake.

Dietary Inflammatory Index of Obese Individuals with Obstructive Sleep Apnea: A Descriptive Study.

The objective of the present study was to describe the dietary inflammatory profile and its correlations with sleep parameters of obese individuals with obstructive sleep apnea (OSA). Forty individuals underwent nocturnal polysomnography, anthropometric measurements, body composition by plethysmography, assessment of food consumption by three-day food records, and blood collection for the lipid, glycemic and hormonal profile. Food consumption data were evaluated semiquantitatively, quantitalively assessment, and calculation of the dietary inflammatory index (DII) was perfomed. The results demonstrated a predominantly proinflammatory dietary profile. The participants showed a low intake of fruit and vegetables. Additionally, a low consumption of fiber, magnesium, vitamin D, and vitamin E was observed, although there was an adequate distribution of macronutrients. In conclusion, although the inflammatory profile did not correlate with OSA, the study showed a directly proportional relationship between adequate dietary patterns and better sleep quality.

Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea: results from the international sleep apnea global interdisciplinary consortium.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA. METHODS: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy." RESULTS: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders. CONCLUSIONS: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals.

How do phases of the menstrual cycle affect sleep? A polysomnographic study of the EPISONO database.

PURPOSE: Our study aimed to evaluate the impact of the menstrual cycle stages, especially menses, on sleep, inflammatory mediators, fatigue, anxiety, depression, and quality of life. METHODS: We used data from the EPISONO study cohort, selecting 96 women who had undergone one-night polysomnography. The women were distributed in three groups according to the time point of the menstrual cycle on the polysomnography night: menses, mid/late follicular phase, and luteal phase. The volunteers completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were collected to analyze interleukin 6, tumor necrosis factor-alpha, and C-reactive protein. RESULTS: Sleep efficiency was statistically higher in women in the mid/late follicular group (89.9% ± 9.6) compared to menstrual (83.0% ± 10.8) and luteal (83.7% ± 12.7) groups. The mid/late follicular group presented a statistically significant reduction in sleep onset latency (7.1 ± 7.1 min) compared to the menstrual (22.3 ± 32.4 min) and luteal groups (15.9 ± 14.7 min). No statistical differences among the three groups were observed in other polysomnographic parameters, inflammatory mediators, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. CONCLUSIONS: Our findings demonstrate that the mid/late follicular phase might be beneficial for women's sleep, although there were no statistically changes in inflammatory mediators among the groups.

Understanding Sexual Parasomnias: A Review of the Current Literature on Their Nature, Diagnosis, Impacts, and Management.

Sexual behavior during sleep, known as sexual parasomnias, has captured the interest of researchers and clinicians. These parasomnias involve various sexual activities that occur unconsciously during sleep. Although relatively rare, they can profoundly affect well-being and relationships and can carry legal consequences. Understanding their nature, prevalence, and causes is crucial for advancing knowledge in this field. This article revisits the topic of sexsomnia, presenting new data and discussing cases published from 2007 to 2023. By analyzing these cases, we aim to enhance recognition, diagnosis, and management of sexsomnia, reducing stigma and providing better support for affected individuals.

Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.

The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep.

INTRODUCTION: Vitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. OBJECTIVES: To analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. METHODS: This study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. RESULTS: The mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. CONCLUSIONS: Poor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.

Effect of a lavender essential oil and sleep hygiene protocol on insomnia in postmenopausal women: A pilot randomized clinical trial.

INTRODUCTION: Insomnia and vasomotor symptoms are frequently experienced during the menopausal transition and in postmenopause, worsening sleep maintenance and quality of life. Our study evaluated the use of lavender essential oil and sleep hygiene guidance on quality of life, sleep patterns and self-reported hot flashes in postmenopausal women with insomnia diagnosis. METHODS: This study is part of a larger experimental, double-blind, randomized controlled trial. We included 35 postmenopausal women with a diagnosis of insomnia who were distributed in two groups: A Placebo group (sunflower oil) and an Aroma group (Lavandula angustifolia essential oil); both inhaled the oils before bedtime for 29 days. The groups received sleep hygiene guidelines and weekly follow-up. Validated questionnaires were used to assess the effect of the intervention, and a sleep diary was used to assess sleep onset latency (SOL), total sleep time (TST), and sleep efficiency (SE) daily. Participants who complained of vasomotor symptoms at baseline kept a daily record of their frequency and intensity. RESULTS: All participants benefited in almost all domains of quality of life and in the self-assessed TST and SE. The Aroma group achieved a significant improvement in their overall quality of life score over time. No differences were observed in respect of the hot flashes record and daytime sleepiness. CONCLUSIONS: The aromatherapy intervention was effective in improving the overall quality of life in the Aroma group. Moreover, the sleep diary and sleep hygiene instructions helped all participants to, respectively, self-assess and improve their sleep patterns.

Sleep patterns according to genetically determined ethnicity in the population of São Paulo, Brazil.

Sleep is a behavior expressed differently for each individual. However, studies have shown that some ethnic groups express common sleep patterns, which can be observed in different ethnic groups. Previous studies have shown the existence of sleep disparities in populations of different ethnicities. Most of these studies have considered self-reported ethnicity and assessed sleep subjectively. Therefore, the aim of this study was to evaluate sleep disparities in different ethnic groups based on an analysis of genetic ancestry and the use of objective sleep evaluation. To do this, we used data from the São Paulo Epidemiologic Sleep Study (EPISONO), which was undertaken in Brazil, a country that is known for its ethnic/racial diversity. All individuals completed a series of questionnaires, underwent full polysomnography and had their blood collected for DNA extraction. After genotyping and identifying samples with high-quality DNA suitable for genetic analysis, 31 ancestry-informative markers (AIMs) were selected. These markers exhibited substantial allelic frequency differences, enabling the characterization of the three primary founding populations of modern Brazil - Europeans, West-Africans, and Native Americans. Through this analysis, the genetic contribution of each of these ancestral groups was identified in respect of each participant. Based on this, a latent class cluster analysis (LCCA) was performed to define the three clusters that best classified the sample according to ethnic group: African (n = 255), Caucasian (n = 668) and Native American (n = 83). Applying the adjusted model for the confounding variables (age, socio-economic class and sex), statistically significant differences in sleep variables between ethnicities were found. Africans had higher sleep latency compared to the other groups (ß = 4.46, CI = 1.18 to 7.74 and ß = 7.83, CI = 3.50 to 12.15), while Caucasians had longer total sleep time (ß = -16.47, CI = -29.94 to -2.99) and better sleep efficiency (ß = -2.19, CI = -4.35 to -0.02) compared to Africans. Regarding the respiratory arousals index (ß = -1.11, IC = -2.07 to -0.16) and periodic leg movements index (ß = -7.48, CI = -12.08 to -2.88), both were higher among Caucasians compared to Africans. We were able to conclude that genetic ancestry might modulate sleep structure and the occurrence of sleep disorders.

Changes in behavioral and cognitive abilities after rapid maxillary expansion in children affected by persistent snoring after long-term adenotonsillectomy: A noncontrolled study.

INTRODUCTION: The objective of this study was to verify changes in behavioral abilities and cognitive functions after rapid maxillary expansion (RME) in children with refractory sleep-disordered breathing (SDB) in the long term after adenotonsillectomy. METHODS: A prospective clinical trial study using RME therapy was conducted. Participant inclusion criteria were children who had adenotonsillectomy with maxillary transverse deficiency and persistent SDB (obstructive apnea-hypopnea index ≥1). The study included 24 children aged 5-12 years, and of these 24 children, 13 had primary snoring and 11 had obstructive sleep apnea. The patients underwent laryngeal nasofibroscopy and a complete polysomnography. In addition, patients completed the Obstructive Pediatric Sleep Questionnaire and Obstructive Sleep Apnea 18-Item Quality-of-Life Questionnaire. Behavioral and neurocognitive tests were also completed before and after RME. RESULTS: The Obstructive Pediatric Sleep Questionnaire and Obstructive Sleep Apnea 18-Item Quality-of-Life scores showed a statistically significant decrease in both groups (P <0.001) after RME. The results showed that neurocognitive and behavioral parameters (Child Behavior Checklist scale) were similar in primary snoring and obstructive sleep apnea (OSA) groups before RME. In the OSA group, the mean scores of the "Somatic" and "Aggressiveness" domains decreased significantly (P <0.05). The cognitive functions did not register significant differences pre- and post-RME in any of the cognitive functions, except for visuospatial function in the OSA group. CONCLUSIONS: The noncontrolled design was a major limitation of our study. The need for treatment for SDB should consider the association of symptoms and behavioral disturbances with the child's obstructive apnea-hypopnea index. RME might prove to be an alternative treatment for children with SDB refractory to adenotonsillectomy, improving quality of life and behavioral aspects. However, a larger sample size with a control group is needed to substantiate these claims.