History of symptoms consistent with REM sleep behavior disorder in a population with Parkinson's Disease.

REM Sleep Behavioral Disorder (RBD) is a parasomnia marked by the maintenance of muscle tone during REM sleep. Evidence has placed RBD as one of the possible prodromal stages of Parkinson's Disease (PD), but data on the proportion of people with PD who have had symptoms of RBD are limited. This study aimed to investigate the history of symptoms compatible with RBD in a population with PD. The sample was composed by 73 patients with clinically diagnosed PD being followed up at a reference outpatient setting, compared to 73 age- and sex-matched individuals with no PD. The evaluation of symptoms compatible with RBD was performed using the Brazilian version of the RBD Screening Questionnaire (RBDSQ). The prevalence of symptoms compatible with RBD was 65 % for PD and 10.09 % for controls. The RBDSQ score was significantly higher in the PD group (6.03 ± 0.35) in comparison to the control group (2.38 ± 0.23). The odds ratio for presenting previous RBD-compatible symptoms was 12.09 in favor of positive PD cases. PD diagnosis has the following diagnostic properties in relation to presenting RBD symptoms: sensitivity of 0.65, specificity of 0.86, positive predictive value of 0.82 and negative predictive value of 0.71. In conclusion, the proportion of PD patients showing RBD symptoms is high, corroborating the expected neuroprogression of the disease on a case-control design comprising outpatient PD cases. Clinical practitioners should include evaluations of RBD-compatible symptoms during the PD assessment and, if positive, forward to a sleep specialist.

Associations between real-life light exposure patterns and sleep behaviour in adolescents.

One of the most striking changes in the regulation of sleep-wake behaviour during adolescence is circadian phase delay. Light exposure synchronises circadian rhythms, impacting sleep regulation, however, the influence of real-life light exposure on sleep variations remains less clear. We aimed to describe the sleep and light exposure patterns of high school students with comparable schedules and socio-economic backgrounds, and to evaluate whether there was any association between them, considering chronotype. We analysed five school days and two free days of actigraphy records, from 35 adolescents (24 female, mean age: 16.23 ± 0.60). The sample was described using the Sleep Regularity Index (SRI), chronotype (actigraphy MSFsc), and self-reported diurnal preference (Morning/Evening Scale). Regression models were constructed to assess the impact of light exposure (daytime and nighttime) on subsequent sleep episodes; and to confirm whether the associations could be an indirect consequence of chronotype. Despite following similar routines, the SRI varied considerably (48.25 to 88.28). There was compatibility between the actigraphy proxy for chronotype and the self-reported diurnal preference, extracted using the circadian rhythm scale for adolescents. Less light exposure during the day was associated with later sleep onset and shorter sleep duration. An increase of 100 lux in average daytime light exposure advance of 8.08 minutes in sleep onset and 7.16 min in sleep offset. When the regressions were controlled for chronotype, these associations persisted. These findings facilitate discussions regarding the behavioural aspect of the impact of real-life light exposure on sleep and its potential as a target for interventions aiming to enhance adolescents' sleep quality.

The influence of phototherapy on circadian melatonin and sleep regulation and potential benefits of these pathways in the management of vitiligo: a narrative review : Vitiligo, phototherapy, sleep and melatonin.

Ultraviolet B narrow band (UVB-NB) phototherapy is the gold standard treatment for vitiligo, primarily due to its immunomodulatory effects. Additionally, it may influence circadian melatonin balance, that may indirectly induce sleep regulation, which in turn could potentially contribute to vitiligo improvement. The association between melatonin, vitiligo and phototherapy has been little investigated. The aim of this study was to evaluate the current evidence regarding the effects of circadian melatonin regulation and sleep, particularly during vitiligo treatment with phototherapy. We undertook a narrative review to synthetize the evidence on this association through the MEDLINE/PubMed database, using combined search terms: melatonin, vitiligo, phototherapy, and circadian rhythm (sleep). A total of 56 articles were included. There are few studies on this relationship, and conflicting findings. Some studies have suggested that UV exposure and phototherapy might benefit vitiligo by stimulating melanocytes, which have melatonin receptors, and this could potentially synchronize the circadian regulation of melatonin. This improved melatonin balance could result in better sleep quality further enhancing the antiinflammatory properties of melatonin and contributing to vitiligo improvement. Less is known about the possible effects of the use of topical melatonin, with or without phototherapy, to treat vitiligo lesions. In conclusion, there is some evidence that circadian melatonin regulation plays an important role in the course of vitiligo, both through sleep regulation and its anti-inflammatory properties. The evidence suggests that the systemic and physiological properties of melatonin, especially its circadian behavior regulated by phototherapy, may be more effective in respect of vitiligo improvement than the use of topical melatonin. However, the effects of the oral intake of melatonin are less clear. Phototherapy, as a potential modulator of circadian melatonin rhythm, that influences sleep and clinical improvement of vitiligo, needs further examination, as does the use of melatonin as an adjuvant treatment to UVB phototherapy in vitiligo.

Exploring the Link between Premature Ovarian Insufficiency, Insomnia and Circadian Pathways.

OBJECTIVE: To establish an interaction network for genes related to premature ovarian insufficiency (POI) and insomnia, and to identify biological processes that connect POI to the physiological clock. METHODS: Previously reported lists of genes associated to POI and insomnia were contrasted and their intersection was used as input on protein-protein interaction analyses. POI-associated genes were contrasted with gene expression markers for neural circadian control and enriched pathways among their shared content were dissected. RESULTS: The functional network generated from the intersection between POI and insomnia gene lists pointed to the central nervous system as the most relevant cellular context for this connection. After identifying POI-associated genes that play a role in neural circadian patterns, we observed the disruption of pathways related to the hypothalamic-pituitary-gonadal axis as the major genetic link between ovarian function and circadian neural circuits. CONCLUSIONS: These findings highlight neurological mechanisms that support the POI-insomnia interplay.

Artificial Intelligence, the Production of Scientific Texts, and the Implications for Sleep Science: Exploring Emerging Paradigms and Perspectives.

The emergence of artificial intelligence (AI) has revolutionized many fields, including natural language processing, and marks a potential paradigm shift in the way we evaluate knowledge. One significant innovation in this area is ChatGPT, a large language model based on the GPT-3.5 architecture created by OpenAI, with one of its main aims being to aid in general text writing, including scientific texts. Here, we highlight the challenges and opportunities related to using generative AI and discuss both the benefits of its use, such as saving time by streamlining the writing process and reducing the amount of time spent on mundane tasks, and the potential drawbacks, including concerns regarding the accuracy and reliability of the information generated and its ethical use. In respect of both education and the writing of scientific texts, clear rules and objectives and institutional principles must be established for the use of AI. We also consider the positive and negative effects of the use of AI technologies on interpersonal interactions and behavior, and, as sleep scientists, its potential impacts on sleep. Striking a balance between the benefits and potential drawbacks of integrating AI into society demands ongoing research by experts, the wide dissemination of the scientific results, as well as continued public discourse on the subject.

Sleep Debt and Insulin Resistance: What's Worse, Sleep Deprivation or Sleep Restriction?

Objective To evaluate which condition of sleep debt has a greater negative impact on insulin resistance: sleep deprivation for 24 hours or 4 hours of sleep restriction for 4 nights. Materials and Methods In total, 28 healthy male subjects aged 18 to 40 years were recruited and randomly allocated to two groups: sleep deprivation (SD) and sleep restriction (SR). Each group underwent two conditions: regular sleep (11 pm to 7 am ) and total sleep deprivation for 24 hours (SD); regular sleep (11 pm to 7 am ) and 4 nights of sleep restriction (SR) (1 am to 5 am ). The oral glucose tolerance test (OGTT) was performed, and baseline glucose, insulin, free fatty acids (FFAs), and cortisol were measured. In addition, the area under the curve (AUC) for glucose and insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the Matsuda Index (Insulin Sensitivity Index, ISI) were calculated. Results Glucose and insulin had a similar pattern between groups, except at the baseline, when insulin was higher in the sleep debt condition of the SR when compared with the SD ( p < 0.01). In the comparison between regular sleep and sleep debt, the SD had a higher insulin AUC ( p < 0.01) and FFAs ( p = 0.03) after sleep deprivation, and insulin and the insulin AUC increased ( p < 0.01 for both), while the ISI decreased ( p = 0.02) after sleep restriction in the SR. In baseline parameters covariate by the condition of regular sleep, insulin ( p = 0.02) and the HOMA-IR ( p < 0.01) were higher, and cortisol ( p = 0.04) was lower after sleep restriction when compared with sleep deprivation. Conclusion Sleep restriction for 4 consecutive nights is more detrimental to energy metabolism because of the higher insulin values and insulin resistance compared with an acute period of sleep deprivation of 24 hours.

Altered sleep and diurnal consequences in women with dysmenorrhea: study from the EPISONO database.

PURPOSE: Our study aimed to identify alterations in sleep, inflammatory mediators, fatigue and quality of life in women with dysmenorrhea and compare them to women without dysmenorrhea. METHODS: The sample comprised 328 women from a Brazilian cross-sectional sleep study, EPISONO (2007), who had undergone 1-night polysomnography (PSG) type I and completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were used to assess levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The 2 groups were distributed based on the presence or absence of dysmenorrhea symptoms. RESULTS: Sleep efficiency was significantly lower in the group of women with dysmenorrhea (82.5% ± 13.8) compared to the non-dysmenorrhea group (86.2% ± 10.9). Dysmenorrhea was associated with significantly higher scores of fatigue and worse scores in the physical quality of life. No statistical differences were detected in inflammatory markers between the 2 groups. DISCUSSION: Fatigue and physical quality of life were presented in women with dysmenorrhea, as was reduced sleep efficiency, although no alteration on inflammatory markers were observed. CONCLUSION: These findings show that dysmenorrhea can have a deleterious effect on women's sleep, with repercussions on daily routines and quality of life.

Sleep disturbances associated with DEAF1 pathogenic variants.

Neurodevelopmental disorders and sleep disturbances share genetic risk factors. DEAF1 genetic variants are associated with rare syndromes in which sleep disturbances are commonly reported, yet the specific sleep disorders in these patients, and the molecular mechanisms underlying this association, are unknown. We aimed to pinpoint specific biological processes that may be disrupted by pathogenic variants in this gene, comparing a list of DEAF1 regulatory target genes with a list of insomnia-associated genes, and using the intersect gene list as the input for pathway enrichment analysis. Thirty-nine DEAF1 regulatory targets were also identified as insomnia-associated genes, and the intersecting gene list was found to be strongly associated with immune processes, ubiquitin-mediated proteolysis pathways and regulation of the cell cycle. This preliminary study highlights pathways that may be disrupted by DEAF1 pathogenic mutations and might be putative factors underlying the manifestation of insomnia in patients harboring such variants.

Subjective sleep assessment in individuals with SYNGAP1-associated syndrome.

STUDY OBJECTIVES: Sleep disturbances are common in neurodevelopmental disorders (NDDs), affecting patients and caregivers' quality of life. SYNGAP1-associated syndrome, a rare NDD, is marked by intellectual disability, developmental delay, epilepsy, and sleep issues. However, research on sleep quality in these individuals is limited. This study aimed to evaluate genetic variants, epilepsy, and sleep patterns in SYNGAP1-associated syndrome patients and their caregivers. METHODS: An online survey was applied to 11 caregivers of individuals diagnosed with SYNGAP1-associated syndrome. Specific clinical inquiries were included, addressing childbirth, previous surgeries, and medication use. Inquiries about epilepsy included type of epilepsy, type and frequency of seizures, anti-seizure medications, and complementary non-pharmacological treatments. Children's Sleep Habits Questionnaire (CSHQ) was applied to assess the patients' sleep profile. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of caregivers. RESULTS: Genetic analysis showed heterozygous mutations in SYNGAP1, often leading to loss of function. Epilepsy was present in 82% of participants, with 77.8% having drug-resistant seizures. Using the Children's Sleep Habits Questionnaire (CSHQ), 81.8% of patients exhibited poor sleep habits, including bedtime resistance, anxiety, night awakenings, parasomnias, and daytime sleepiness. Caregivers also reported poor sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). CONCLUSIONS: This study highlights the high prevalence of epilepsy and sleep problems in SYNGAP1-associated syndrome, impacting both patients and caregivers. Further research is crucial to understand the syndrome's effects on sleep disturbances, emphasizing the need for targeted interventions to improve sleep quality in individuals with rare genetic syndromes and their caregivers.

Sleep is associated with telomere shortening: A population-based longitudinal study.

As the chronological age increases, there is a decrease in the telomere length (TL). Associations between TL and age-related diseases have been described. Since the major pathophysiological factors related to inadequate sleep (including sleep complaints and sleep disorders) contribute to the exacerbation of inflammation and oxidative stress, an association of sleep and TL has been proposed. The aim of this study was to evaluate the association between sleep-related variables with TL in a longitudinal framework. We used data derived from the EPISONO cohort, which was followed over 8 years. All individuals answered sleep-related questionnaires, underwent a full-night polysomnography (PSG), and had their blood collected for DNA extraction. The TL was measured through a quantitative real time polymerase chain reaction. Age, sex, body mass index (BMI), smoking, physical activity status, and the 10 principal components (ancestry estimate) were considered covariables. Of the 1042 individuals in the EPISONO cohort, 68.3% agreed to participate in the follow-up study (n = 712). Baseline SpO2 (ß = 0.008, p = 0.007), medium SpO2 (ß = 0.013, p = 0.013), and total sleep time <90% (ß = -0.122, p = 0.012) had an effect on TL from the follow-up. The 8 year TL attrition was inversely associated with total sleep time, sleep efficiency, sleep architecture variables, wake after sleep onset, arousal index, oxygen-related variables baseline, and the presence of obstructive sleep apnea (OSA). We conclude that individuals with worse sleep quality, alterations in sleep architecture, and OSA had greater TL attrition over the 8 years. Using a longitudinal approach, these findings confirm previous cross-sectional evidence linking sleep with accelerated biological ageing.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer's disease older adults.

BACKGROUND: Few studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). METHODS: This was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). RESULTS: We allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DISCUSSION: The amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

The Impact of Sleep: From Ancient Rituals to Modern Challenges.

Although sleep is crucial for mental and physical health, insufficient sleep is a growing problem in our modern society. In general, adults need approximately eight hours of sleep per night, but this is often unfeasible nowadays. This sleep restriction has been observed, and it has worsened, throughout the past two centuries; therefore, it is more attributed to socioeconomic changes than to biological adaptations. The most important factors to contribute to this sleep restriction were the popularization of artificial light and industrialization. The present manuscript briefly overviews, from a socioanthropological perspective, the reasons why sleep has been impacted, disclosing its effects on individuals and on society.

Kinesin binding as a shared pathway underlying the genetic basis of male factor infertility and insomnia.

OBJECTIVE: To study whether male factor infertility and insomnia share genetic risk variants and identify any molecular, cellular, and biologic interactions between these traits. DESIGN: The in silico study was performed. Two lists of genetic variants were manually curated through a literature review, one of those associated with male factor infertility and the other with insomnia. Genes were assigned to these variants to compose male factor infertility-associated (454 genes) and insomnia-associated (921 genes) gene lists. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Enrichment of biologic pathways and protein-protein interaction analysis. RESULT(S): Twenty-eight genes were common to both lists, representing a greater overlap than would be expected by chance. In the 28 genes contained in the intersection list, there was a significant enrichment of pathways related to kinesin binding. A protein-protein interaction analysis using the intersection list as input retrieved 25 nodes and indicated that two of them were kinesin-related proteins (PLEKHM2 and KCL1). CONCLUSION(S): The shared male factor infertility and insomnia genes, and the biologic pathways highlighted in this study, suggest that further functional investigations into the interplay between fertility and sleep are warranted.

Bimodal diurnal preference in undergraduate students is associated with negative health and sleep outcomes.

The bimodal preference is a fourth diurnal preference proposed by re-scoring the Morningness-Eveningness Questionnaire. The present work aimed to describe the prevalence of the bimodal preference in a sample of undergraduate students and to characterize the bimodal type in terms of their health and sleep-related outcomes. A web-based cross-sectional study conducted between September 2018 and March 2021 (convenience sampling method). The sample was composed of undergraduate students who completed an electronic form that included the Morningness and Eveningness Questionnaire, the Pittsburgh Sleep Quality Index, the Self-Compassion Scale, the Epworth Sleepiness Scale, the Hospital Anxiety and Depression Scale, and the World Health Organization Subjective Well-Being Index. The final sample consisted of 615 students (82% female, mean age: 23.4 ± 6.5 years), of whom 108 (18%) had positive bimodality indexes. Bimodal subjects comprised 48 students, 8% of the total sample. Bimodal subjects had poorer subjective sleep quality, more daytime sleepiness, lower subjective well-being, greater anxiety and depression symptoms, and lower self-compassion than morning and/or intermediate types; they did not differ from evening types. The description of bimodal diurnal preference in this population may be of interest for the design of academic policies more in line with the circadian reality of students.

Insomnia Symptoms and Menstrual Health: Is There a Link in Women During Reproductive Phase of Life?

OBJECTIVES: To investigate the association between insomnia severity symptoms and menstrual health, fatigue and anxiety symptoms in women at reproductive age. METHOD: We used data from EPISONO (2007), an epidemiological study from the city of São Paulo, Brazil. Women completed the Insomnia Severity Index (ISI), the Chalder Fatigue Scale (CFS), and the Beck Anxiety Inventory (BAI) to obtain information about insomnia, fatigue, and anxiety symptoms. For menstrual health, we collected information using our Institutional Women's Questionnaire about menstrual flow and duration, the presence of pain during menstruation and menstrual cycle regularity. The statistical analysis was performed using ordinal logistic regression, considering p < .05. RESULTS: Of the 1,042 participants, only 282 women met the inclusion criteria to participate in this study. The mean age was 34.4 years (SD ± 8.36), and the body mass index (BMI) was 25.7 (SD ± 5.39). According to the model, a 1-unit higher CFS score increased the odds of having more insomnia symptoms in the ISI (OR = 1.170; 95% CI=[1.073; 1.279]; p < .001). In the same way, a 1-unit higher BAI score increased the chance of presenting insomnia symptoms, according to the ISI (OR = 1.072; 95% CI=[1.042; 1.104]; p < .001). The menstrual variables did not represent statistical significance in the model. CONCLUSIONS: Fatigue and anxiety symptoms were associated with insomnia symptoms; however, no association was observed between menstrual health and insomnia. The need to examine sleep when there are sleep complaints is essential to provide an accurate diagnosis that facilitates appropriate treatment and to provide better sleep quality for women.

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.