Sex Differences in Insomnia and Circadian Rhythm Disorders: A Systematic Review.

Insomnia and circadian rhythm disorders are increasingly common in modern society and lead to significant challenges for people's health and well-being. Some studies suggests that men and women differ in neurohormonal secretion, biological processes, and brain morphology. Thus, such differences may affect the etiology, manifestation, and course of sleep disorders, including insomnia and circadian rhythm. This systematic review aims to synthesize the existing literature on sex differences in insomnia and circadian rhythm disorders. PubMed, MEDLINE, Epistemonikos, and Cochrane databases were searched for articles published from inception until 5 September 2023, not older than five years. We performed a systematic search using MESH and non-MESH queries: (sex differences) or (male and female differences) or (men and women differences) or (men and women) AND (insomnia) or (sleep wake disorder*) or (sleep wake rhythm disorder*) or (circadian rhythm disorder*) or (sleep cycle disruption) or (sleep cycle disorder*). Out off 2833 articles screened, 11 studies were included. The prevalence of insomnia is higher among women, and their sleep is more regular and stable compared to men. Studies evaluating the impact of the stressful situation associated with the lockdown on women's and men's insomnia present discordant results concerning sex differences. Women's circadian rhythm was found to be more stable and less fragmented than men's. However, the progression of peak activity time with age was more pronounced in men. The current literature suggests that risk factors for insomnia and circadian rhythm disorders affect men and women differently. These include cerebrovascular and cardiometabolic factors, shift work, and infections. The long-term effects of insomnia seem to be more relevant for the male sex, shortening lifespan more than in women. By summarizing and analyzing existing studies, we highlight the need for further research to improve understanding of the interaction between sex and sleep.

Melatonin attenuates fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice.

Melatonin is a neurohormone synthesized by the pineal gland to regulate the circadian rhythms and has proven to be effective in treating drug addiction and dependence. However, the effects of melatonin to modulate the drug-seeking behavior of fentanyl and its underlying molecular mechanism is elusive. This study was designed to investigate the effects of melatonin on fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice. The accompanying changes in the expression of Brain and Muscle Arnt-Like (BMAL1), tyrosine hydroxylase (TH), and monoamine oxidase A (MAO-A) in relevant brain regions including the suprachiasmatic nucleus (SCN), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus (Hip) were investigated by western blot assays to dissect the mechanism by which melatonin modulates fentanyl - induced behavioral sensitization and circadian rhythm disorders. The present study suggest that fentanyl (0.05, 0.1 and 0.2 mg/kg) could induce behavioral sensitization and melatonin (30.0 mg/kg) could attenuate the behavioral sensitization and circadian rhythm disorders in mice. Fentanyl treatment reduced the expression of BMAL1 and MAO-A and increased that of TH in relevant brain regions. Furthermore, melatonin treatment could reverse the expression levels of BMAL1, MAO-A, and TH. In conclusion, our study demonstrate for the first time that melatonin has therapeutic potential for fentanyl addiction.

VX-765 Alleviates Circadian Rhythm Disorder in a Rodent Model of Traumatic Brain Injury Plus Hemorrhagic Shock and Resuscitation.

Severe traumatic brain injury (TBI) can result in persistent complications, including circadian rhythm disorder, that substantially affect not only the injured people, but also the mood and social interactions with the family and the community. Pyroptosis in GFAP-positive astrocytes plays a vital role in inflammatory changes post-TBI. We determined whether VX-765, a low molecular weight caspase-1 inhibitor, has potential therapeutic value against astrocytic inflammation and pyroptosis in a rodent model of TBI plus hemorrhagic shock and resuscitation (HSR). A weight-drop plus bleeding and refusion model was used to establish traumatic exposure in rats. VX-765 (50 mg/kg) was injected via the femoral vein after resuscitation. Wheel-running activity was assessed, brain magnetic resonance images were evaluated, the expression of pyroptosis-associated molecules including cleaved caspase-1, gasdermin D (GSDMD), and interleukin-18 (IL-18) in astrocytes in the region of anterior hypothalamus, were explored 30 days post-trauma. VX-765-treated rats had significant improvement in circadian rhythm disorder, decreased mean diffusivity (MD) and mean kurtosis (MK), increased fractional anisotropy (FA), an elevated number and branches of astrocytes, and lower cleaved caspase-1, GSDMD, and IL-18 expression in astrocytes than TBI + HSR-treated rats. These results demonstrated that inhibition of pyroptosis-associated astrocytic activations in the anterior hypothalamus using VX-765 may ameliorate circadian rhythm disorder after trauma. In conclusion, we suggest that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI.

Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Social and circadian rhythm dysregulation and suicide: A systematic review and meta-analysis.

This systematic review of 52 studies provides a quantitative synthesis of the empirical literature on social and circadian rhythm correlates of suicidal thoughts and behaviors (STB). Small-to-medium pooled effect sizes were observed for associations between evening chronotype and STB and suicidal ideation (SI), although the pooled effect size diminished when accounting for publication bias. Three studies employed longitudinal designs and suggested eveningness was predictive of future STB, with a small-to-medium effect size. Social rhythm irregularity was also a significant correlate of STB with pooled effect sizes in the medium range. Overall circadian rhythm disruption was not associated with STB, although certain circadian rhythm metrics, including mean daytime activity, circadian rhythm sleep-wake disorder diagnosis, and actigraphy-assessed amplitude were associated with STB. Pooled effect sizes for these indices were in the medium to large range. There is a need for additional longitudinal research on actigraphy-based circadian parameters and objective markers of circadian phase (i.e., dim-light melatonin onset) to gain a clearer understanding of associations of endogenous circadian function and STB beyond that which can be captured via self-report.

The efficacy of a transdiagnostic sleep intervention for outpatients with sleep problems and depression, bipolar disorder, or attention deficit disorder: study protocol for a randomized controlled trial.

BACKGROUND: Patients with mental disorders have a higher prevalence of sleep problems than the general population. Sleep problems may include insomnia, circadian rhythm disorders, or hypersomnia. A transdiagnostic approach combining cognitive behavioral therapy for insomnia (CBT-I) with chronotherapy addressing a broad range of sleep problems has shown promising results in a limited number of studies. The aim of the study is to investigate the efficacy of a transdiagnostic sleep intervention for patients with sleep problems comorbid to bipolar disorder, unipolar depression, or attention deficit disorders. The primary hypothesis is that the intervention improves sleep quality compared with a control group. The secondary hypotheses are that the intervention increases subjective and objective sleep efficiency, reduces sleep onset latency, wake after sleep onset, number of awakenings, and severity of insomnia; and that it improves well-being, personal recovery, work ability, and consumption of sleep medication compared with a control group. METHODS: The study is a randomized controlled trial enrolling 88 outpatients with bipolar disorder, major depression, or attention deficit disorder with symptoms of various sleep problems (insomnia, circadian rhythm disorders, or hypersomnia). Patients are allocated to either an intervention group receiving six sessions of transdiagnostic sleep treatment or to a control group receiving a single session of sleep hygiene education. Assessments are made at baseline, at week two, and after 6 weeks in both groups. Actigraphy is performed continuously throughout the 6-week study period for all patients. The primary outcome is changes in the subjective appraisal of sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes are changes in sleep efficiency, sleep onset latency, wake after sleep onset, number of nocturnal awakenings (based on actigraph and sleep diary data), changes in insomnia severity (Insomnia Severity Index), well-being (WHO-5 Well-Being Index), personal recovery (INSPIRE-O), work ability (Work Ability Index), and consumption of sleep medication (sleep-diaries). DISCUSSION: The study was initiated in 2022 and the inclusion period will continue until mid-2024. The results may have implications for the development and implementation of additional treatment options for patients with mental disorders and comorbid sleep problems. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05406414. Registered on June 6, 2022.

Loss of Dec1 inhibits alcohol-induced hepatic lipid accumulation and circadian rhythm disorder.

Chronic alcohol exposure increases liver damage such as lipid accumulation and hepatitis, resulting in hepatic cirrhosis. Chronic alcohol intake is known to disturb circadian rhythms in humans and animals. DEC1, a basic helix-loop-helix transcription factor, plays an important role in the circadian rhythm, inflammation, immune responses, and tumor progression. We have previously shown that Dec1 deficiency inhibits stresses such as periodontal inflammation and perivascular fibrosis of the heart. However, the significance of Dec1 deficiency in chronic alcohol consumption remains unclear. In the present study, we investigated whether the biological stress caused by chronic alcohol intake is inhibited in Dec1 knockout mice. We treated control and Dec1 knockout mice for three months by providing free access to 10% alcohol. The Dec1 knockout mice consumed more alcohol than control mice, however, we observed severe hepatic lipid accumulation and circadian rhythm disturbance in control mice. In contrast, Dec1 knockout mice exhibited little effect on these outcomes. We also investigated the expression of peroxisome proliferator-activated receptors (PPARs) and AMP-activated protein kinase (AMPK), which are involved in the regulation of fatty acid metabolism. Immunohistochemical analysis revealed increases of phosphorylation AMPK and PPARa but decreases PPARg in Dec1 knockout mice compared to that in control mice. This indicates a molecular basis for the inhibition of hepatic lipid accumulation in alcohol-treated Dec1 knockout mice. These results suggest a novel function of Dec1 in alcohol-induced hepatic lipid accumulation and circadian rhythm disorders.

Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBß in Human Osteosarcoma Cell Cultures.

REV-ERBα and its paralog, REV-ERBß, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBß to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer.

Pressure Building Against the Clock: The Impact of Circadian Misalignment on Blood Pressure.

PURPOSE OF REVIEW: Misalignment between the endogenous biological timing system and behavioral activities (i.e., sleep/wake, eating, activity) contributes to adverse cardiovascular health. In this review, we discuss the effects of recurring circadian misalignment on blood pressure regulation and the implications for hypertension development. Additionally, we highlight emerging therapeutic approaches designed to mitigate the negative cardiovascular consequences elicited by circadian disruption. RECENT FINDINGS: Circadian misalignment elicited by work schedules that require individuals to be awake during the biological night (i.e., shift work) alters 24-h blood pressure rhythms. Mechanistically, circadian misalignment appears to alter blood pressure via changes in autonomic nervous system balance, variations to sodium retention, dysregulation of endothelial vasodilatory responsiveness, and activation of proinflammatory mechanisms. Recurring circadian misalignment produced by a mismatch in sleep timing on free days vs. work days (i.e., social jetlag) appears to have no direct effects on prevailing blood pressure levels in healthy adults; though, circadian disruptions resulting from social jetlag may increase the risk of hypertension through enhanced sympathetic activation and/or obesity. Furthermore, social jetlag assessment may be a useful metric in shift work populations where the magnitude of circadian misalignment may be greater than in the general population. Circadian misalignment promotes unfavorable changes to 24-h blood pressure rhythms, most notably in shift working populations. While light therapy, melatonin supplementation, and the timing of drug administration may improve cardiovascular outcomes, interventions designed to target the effects of circadian misalignment on blood pressure regulation are warranted.

Pediatric Intensive Care Unit related Sleep and Circadian Dysregulation: a focused review.

The pediatric intensive care unit (PICU) is bright, loud, and disruptive to children. Strategies to improve the sleep of adults in the ICU have improved delirium and mortality rates. Children need more sleep than adults for active growth, healing, and development when well; this is likely true when they are critically ill. This review was performed to describe what we know in this area to date with the intent to identify future directions for research in this field. Since the 1990s, 16 articles on 14 observational trials have been published investigating the sleep on a total of 312 critically ill children and the melatonin levels of an additional 144. Sleep measurements occurred in 9 studies through bedside observation (n = 2), actigraphy (n = 2), electroencephalogram (n = 1) and polysomnography (n = 4), of which polysomnography is the most reliable. Children in the PICU sleep more during the day, have fragmented sleep and disturbed sleep architecture. Melatonin levels may be elevated and peak later in critically ill children. Early data suggest there are at-risk subgroups for sleep and circadian disruption in the PICU including those with sepsis, burns, traumatic brain injury and after cardiothoracic surgery. The available literature describing the sleep of critically ill children is limited to small single-center observational studies with varying measurements of sleep and inconsistent findings. Future studies should use validated measurements and standardized definitions to begin to harmonize this area of medicine to build toward pragmatic interventional trials that may shift the paradigm of care in the pediatric intensive care unit.

[Association between circadian rhythm disorder and comorbidity of anxiety and depression in adolescents].

Adolescents are in a transition period from children to adults, during which they are prone to a variety of emotional disorders, with anxiety and depression being the most common disorders. Anxiety and depressive symptoms are highly correlated and the comorbidity of anxiety and depression is common. At the same time, the most prominent behavioral changes in adolescence are the emergence of getting up late and sleeping late, and the circadian rhythm begins to delay. Previous studies have shown that circadian rhythm is closely related to anxiety and depression, but the association between circadian rhythm disorder and comorbidity of anxiety and depression remains unclear. This article reviews the prevalence, association and potential biological mechanism of circadian rhythm disorder and comorbidity of anxiety and depression in adolescents, so as to provide a possible reference for the prevention and control of comorbidity of anxiety and depression in adolescents.

A Study on the Amelioration of Circadian Rhythm Disorders in Fat Mice Using High-Protein Diets.

This innovative study investigates the effects of high-protein diets (milk protein) on the circadian rhythm of hepatic lipid metabolism. We aimed to understand how high-protein interventions regulate biological clock genes, maintain lipid metabolism balance, and affect the circadian rhythm of antioxidant levels in vivo. We divided 120 SPF-class C57BL/6J mice into the control, high-fat/low-protein (HF-LP), and high-fat/high-protein (HF-HP) groups. Mice were sacrificed during active (2 a.m. and 8 a.m.) and rest periods (2 p.m. and 8 p.m.). In the HF-LP group, hepatic lipid anabolic enzymes were consistently expressed at high levels, while key lipolytic enzymes slowly increased after feeding with no significant diurnal differences. This led to an abnormal elevation in blood lipid levels, a slow increase in and low levels of superoxide dismutase, and a rapid increase in malondialdehyde levels, deviating from the diurnal trend observed in the control group. However, high-protein interventions in the HF-HP group restored lipid synthase activity and the expression of key catabolic enzymes, exhibiting a precise circadian rhythm. It also improved the lipid-metabolism rhythm, which was disrupted by the high-fat diet. Overall, high-protein interventions restored the expression of key enzymes involved in lipid metabolism, improving the lipid-metabolism rhythm, which was disrupted by the high-fat diet.

Circadian Rhythm Sleep-Wake Disorders.

OBJECTIVE: This article provides an overview of advances in the understanding of circadian rhythms and the health implications of circadian disruption. LATEST DEVELOPMENTS: Circadian medicine is a relatively new concept, with widespread overlap with many other areas of medicine. Circadian clocks rely on feedback loops that control the expression of many genes. Functional circadian oscillators exist at multiple physiologic levels and facilitate a multimodal clock mechanism. The suprachiasmatic nucleus is the central circadian pacemaker. Peripheral tissues can be entrained by other stimuli (such as food intake) and can uncouple from the suprachiasmatic nucleus pacemaker; this discovery may provide new therapeutic options for circadian rhythm disorders. Numerous modern developments have altered our circadian clocks and these changes are associated with poor health outcomes. ESSENTIAL POINTS: Circadian clocks are ubiquitous throughout our body and regulate multiple body functions. Several studies have highlighted that circadian disruption can result in significant negative mental and physical health consequences. A deeper understanding of the effects of misalignment between our circadian clocks and the external environment may ultimately have therapeutic implications for our health.

Recent advances in the study of circadian rhythm disorders that induce diabetic retinopathy.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes mellitus and a major cause of blindness in young adults. Multiple potential factors influence DR; however, the exact mechanisms are poorly understood. Advanced treatments for DR, including laser therapy, vitrectomy, and intraocular drug injections, slow the disease's progression but fail to cure or reverse visual impairment. Therefore, additional effective methods to prevent and treat DR are required. The biological clock plays a crucial role in maintaining balance in the circadian rhythm of the body. Poor lifestyle habits, such as irregular routines and high-fat diets, may disrupt central and limbic circadian rhythms. Disrupted circadian rhythms can result in altered glucose metabolism and obesity. Misaligned central and peripheral clocks lead to a disorder of the rhythm of glucose metabolism, and chronically high sugar levels lead to the development of DR. We observed a disturbance in clock function in patients with diabetes, and a misaligned clock could accelerate the development of DR. In the current study, we examine the relationship between circadian rhythm disorders, diabetes, and DR. We conclude that: 1) abnormal function of the central clock and peripheral clock leads to abnormal glucose metabolism, further causing DR and 2) diabetes causes abnormal circadian rhythms, further exacerbating DR. Thus, our study presents new insights into the prevention and treatment of DR.

The effect of shift work on different hematological parameters among healthcare workers.

Shift workers frequently experience alterations in their circadian rhythms, which are correlated with variations in hematological parameters. Changes in blood cells may be related to an individual's health status. Therefore, this study aimed to compare the relationship between shift work and changes in blood cells among a group of healthcare workers in Sri Lanka. A comparative cross-sectional study was conducted among healthcare workers, recruited by a stratified random sampling technique. Socio-demographic data were collected using a structured questionnaire. Venous blood samples were obtained and analyzed for the determination of total and differential blood cell counts. Descriptive statistics were used for the analysis of sociodemographic and hematological parameters. A sample of 37-day workers and 39 shift workers were included in the analysis. The mean ages (years) were not significantly different between the groups (36.8 ± 10.8 vs 39.1 ± 12.0; P = 0.371). Shift employees showed a significantly higher total mean white blood cell count (WBC) of 7548.75 mm-3 compared to day workers' 6869.19 mm-3 (P = 0.027). They also had higher mean absolute counts for all different WBC types (Neutrophils: 3949.2 vs 3557.7 , Lymphocyte: 2756.5 vs 2614.2 , Eosinophil: 317.6 vs 233.4 , Monocytes: 491.63 vs 432.51 , Basophils: 31.68 vs 29.22 ). Shift employees exhibited higher WBC counts than day workers at the same level of work experience. The length of shift work exposure revealed a positive link with neutrophil (r = 0.225 ) and eosinophil counts (r = 0.262 ), whereas these correlations were negative for day workers. Shift workers were associated with higher WBC counts in healthcare workers compared to their day-working counterparts.

Investigation of sleep and circadian rhythm disorders.

Diagnosis of a sleep disorders is multimodal. An overview is presented in this review. The medical history leads to a tentative diagnosis supported by questionnaires, sleep diary and objective methods. Examination may reveal upper airway problems in a patient suspected to have obstructive sleep apnoea or rigidity in an elderly patient with shouting during sleep, suggestive of rapid eye movement sleep behaviour disorder. The choice of diagnostic sleep test is based on the tentative diagnosis. Other tests (e.g., lumbar puncture, brain scan) may be indicated. Wearables pose the advantage of documenting the patients' habitual sleep and circadian rhythm.

Implications from proteomic studies investigating circadian rhythm disorder-regulated neurodegenerative disease pathology.

Neurodegenerative diseases (NDs) affect 15% of the world's population and are becoming an increasingly common cause of morbidity and mortality worldwide. Circadian rhythm disorders (CRDs) have been reported to be involved in the pathogenic regulation of various neurologic diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Proteomic technology is helpful to explore treatment targets for CRDs in patients with NDs. Here, we review the key differentially expressed (DE) proteins identified in previous proteomic studies investigating NDs, CRDs and associated models and the related pathways identified by enrichment analysis. Furthermore, we summarize the advantages and disadvantages of the above studies and propose new proteomic technologies for the precise study of circadian disorder-mediated regulation of ND pathology. This review provides a theoretical and technical reference for the precise study of circadian disorder-mediated regulation of ND pathology.

Navy Sailors Health Behavior: A Multi-Factor Analysis of Circadian Rhythm on Naval Operational Capability.

Objective: The objective of this research was to determine the impact of circadian rhythm disorders on sleep disorders, fatigue and health problems of navy sailors from the perspective of their health behavior. During its voyage, navy crews have obvious problems such as sleep disorders and fatigue, among which the circadian rhythm disorder was the most common. Warning system, special environment at sea, pressure and other factors can lead to the occurrence of circadian rhythm disorders. Methods: The primary data was used in this research with a sample size of 278 and Smart PLS was used for statistical analysis. Results: According to empirical data, the impact of circadian rhythm disorders was significant on sleep disorders, fatigue and health problems of navy sailors. The research is novel in the literature because very few studies have discussed the circadian rhythm disorders in the context of navy sailors. Conclusion: The research implications in the theory are reliable to enhance the body of knowledge of circadian in the significant way. Furthermore, the study has some practical implications to work on to enhance the practices to improve the health of navy sailors during their long time in the sea.

Is obstructive sleep apnea a circadian rhythm disorder?

Obstructive sleep apnea is the most common sleep-related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life and work performance as well as an increased risk of death. Standard treatment seems to have limited effects on cardiovascular and metabolic aspects of the disease, emphasising the need for early diagnosis and additional therapeutic approaches. Recent evidence suggests that the dysregulation of circadian rhythms, processes with endogenous rhythmicity that are adjusted to the environment through various cues, is involved in the pathogenesis of comorbidities. In patients with obstructive sleep apnea, altered circadian gene expression patterns have been demonstrated. Obstructive respiratory events may promote circadian dysregulation through the effects of sleep disturbance and intermittent hypoxia, with subsequent inflammation and disruption of neural and hormonal homeostasis. In this review, current knowledge on obstructive sleep apnea, circadian rhythm regulation, and circadian rhythm sleep disorders is summarised. Studies that connect obstructive sleep apnea to circadian rhythm abnormalities are critically evaluated. Furthermore, pathogenetic mechanisms that may underlie this association, most notably hypoxia signalling, are presented. A bidirectional relationship between obstructive sleep apnea and circadian rhythm dysregulation is proposed. Approaching obstructive sleep apnea as a circadian rhythm disorder may prove beneficial for the development of new, personalised diagnostic, therapeutic and prognostic tools. However, further studies are needed before the clinical approach to obstructive sleep apnea includes targeting the circadian system.