Association between the weight-adjusted-waist index and circadian syndrome in findings from a nationwide study.

Weight-adjusted-waist index (WWI) is an emerging parameter for evaluating obesity. We sought to ascertain the link between WWI and circadian syndrome (CircS). The study population consisted of 8275 eligible subjects who were included in the ultimate analysis from the NHANES 2011-2018. By using multivariable regression models, the association of WWI and CircS was analyzed. In subgroup analysis, we explored the relationship in different groups and tested the stability of the intergroup connection using interaction testing. To investigate whether WWI and CircS had a potential non-linear relationship, smooth curve fittings, and threshold effects tests were also constructed. In a multivariate linear regression model, WWI is significantly positively related to CircS (OR = 1.77, 95% CI 1.50-2.08). Through subgroup analysis and interaction testing, the stability of this positive association was also validated. It was further found that there was an inverted U-shaped association, with a turning point of 11.84, between WWI and CircS. Our findings supported a strong association between WWI values and CircS. Central obesity management is pivotal for preventing or alleviating CircS.

Insomnia and circadian rhythms dysregulation in people who have attempted suicide: correlations with markers of inflammation and suicidal lethality.

INTRODUCTION: Suicide is a widespread problem, with risk factors still a challenge. The aim was to assess correlations among insomnia, circadian rhythm, and inflammatory markers in individuals who attempted suicide. MATERIALS AND METHODS: Consecutive patients hospitalised following an attempted suicide, were assessed. Psychiatric diagnosis (DSM-5-TR Criteria), lethality of the suicide attempt (Suicide Intent Scale-SIS), and inflammatory parameters NLR (neutrophil-lymphocyte ratio) PLR (platelet-lymphocyte ratio), and SII (systemic inflammation index/neutrophil-to-platelet ratio on lymphocytes), were computed. Depressive and manic symptoms (Beck Depression Inventory-BDI-II, Young Mania Rating Scale- YMRS), circadian rhythms disturbances (Biological Rhythms Interview of Assessment in Neuropsychiatry-BRIAN), insomnia symptoms (Insomnia Severity Index-ISI) were assessed together with socio-demographic, clinical and pharmacological data. RESULTS: The final sample included 52 individuals. Patients who experienced insomnia during the preceding two weeks utilised high lethality methods, reported heightened dysregulation of chronobiological rhythms, heightened severity of depression, and elevated levels of inflammatory markers. High lethality was best predicted by insomnia symptoms (OR = 20.1, CI-95% 4.66-87.25, p = 0.001), by disturbances of circadian rhythms (OR = 6.97, CI-95% 1.82-26.66, p = 0.005), and by NLR indices (OR 4.00, CI-95% 1.14-13.99, p = 0.030). CONCLUSIONS: Sleep disturbances may be a risk factor for suicidal lethality, along with markers of inflammation. It is plausible that insomnia and circadian sleep dysregulation may contribute to inflammation, thereby promoting suicidal risk.

Gut Microbiota Mediate the Neuroprotective Effect of Oolong Tea Polyphenols in Cognitive Impairment Induced by Circadian Rhythm Disorder.

Oolong tea polyphenols (OTP) have attracted wide attention due to their ability to reduce inflammatory response, regulate gut microbiota, and improve cognitive function. However, exactly how the gut microbiota modulates nervous system activity is still an open question. We previously expounded that supplementing with OTP alleviated neuroinflammation in circadian rhythm disorder (CRD) mice. Here, we showed that OTP can relieve microglia activation by reducing harmful microbial metabolites lipopolysaccharide (LPS) that alleviate CRD-induced cognitive decline. Mechanistically, OTP suppressed the inflammation response by regulating the gut microbiota composition, including upregulating the relative abundance of Muribaculaceae and Clostridia_UCG-014 and downregulating Desulfovibrio, promoting the production of short-chain fatty acids (SCFAs). Moreover, the use of OTP alleviated intestinal barrier damage and decreased the LPS transport to the serum. These results further inhibited the activation of microglia, thus alleviating cognitive impairment by inhibiting neuroinflammation, neuron damage, and neurotoxicity metabolite glutamate elevation. Meanwhile, OTP upregulated the expression of synaptic plasticity-related protein postsynaptic density protein 95 (PSD-95) and synaptophysin (SYN) by elevating the brain-derived neurotrophic factor (BDNF) level. Taken together, our findings suggest that the OTP has the potential to prevent CRD-induced cognition decline by modulating gut microbiota and microbial metabolites.

Sleep and circadian rhythm dysfunctions in movement disorders beyond Parkinson's disease and atypical parkinsonisms.

PURPOSE OF REVIEW: This review aimed to comprehensively outline sleep and circadian rhythm abnormalities in hyperkinetic movement disorders beyond Parkinson's disease and atypical parkinsonisms, including tremor, dystonia, choreiform movements, tics, and ataxia disorders. RECENT FINDINGS: Insomnia, poor sleep quality, and excessive daytime sleepiness (EDS) are commonly reported in essential tremor, Wilson's disease, tics or Tourette's syndrome, and spinocerebellar ataxia (SCA). REM sleep behavior disorder (RBD) have been observed in Wilson's disease and SCA. A combination of REM and non-REM parasomnias, along with nocturnal stridor with the initiation of sleep and re-entering after awakening, are characterized by undifferentiated Non-REM and poorly structured N2 in anti-IgLON5 disease. Restless legs syndrome (RLS) has been reported commonly in SCAs. Sleep-related dyskinesia has been reported in ADCY5-related disease and GNAO1-related movement disorder. SUMMARY: Sleep problems can manifest as a result of movement disorders, either through direct motor disturbances or secondary nonmotor symptoms. Medication effects must be considered, as certain medications for movement disorders can exacerbate or alleviate sleep disturbances. Distinguishing sleep problems in some diseases might involve pathognomonic symptoms and signs, aiding in the diagnosis of movement disorders.

Circadian dysfunction and cardio-metabolic disorders in humans.

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

The circadian system: A neglected player in neurodevelopmental disorders.

Patients with neurodevelopmental disorders, such as autism spectrum disorder, often display abnormal circadian rhythms. The role of the circadian system in these disorders has gained considerable attention over the last decades. Yet, it remains largely unknown how these disruptions occur and to what extent they contribute to the disorders' development. In this review, we examine circadian system dysregulation as observed in patients and animal models of neurodevelopmental disorders. Second, we explore whether circadian rhythm disruptions constitute a risk factor for neurodevelopmental disorders from studies in humans and model organisms. Lastly, we focus on the impact of psychiatric medications on circadian rhythms and the potential benefits of chronotherapy. The literature reveals that patients with neurodevelopmental disorders display altered sleep-wake cycles and melatonin rhythms/levels in a heterogeneous manner, and model organisms used to study these disorders appear to support that circadian dysfunction may be an inherent characteristic of neurodevelopmental disorders. Furthermore, the pre-clinical and clinical evidence indicates that circadian disruption at the environmental and genetic levels may contribute to the behavioural changes observed in these disorders. Finally, studies suggest that psychiatric medications, particularly those prescribed for attention-deficit/hyperactivity disorder and schizophrenia, can have direct effects on the circadian system and that chronotherapy may be leveraged to offset some of these side effects. This review highlights that circadian system dysfunction is likely a core pathological feature of neurodevelopmental disorders and that further research is required to elucidate this relationship.

The Association between Circadian Syndrome and Frailty in US adults: a cross-sectional study of NHANES Data from 2007 to 2018.

PURPOSE: Frailty and Circadian Syndrome (CircS) are prevalent among the elderly, yet the link between them remains underexplored. This study aims to examine the association between CircS and frailty, particularly focusing on the impact of various CircS components on frailty. MATERIALS AND METHODS: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018. The 49-item Frailty Index (FI) was employed to assess frailty. To understand the prevalence of CircS in relation to frailty, we applied three multivariate logistic regression models. Additionally, subgroup and interaction analyses were performed to investigate potential modifying factors. RESULTS: The study included 8,569 participants. In fully adjusted models, individuals with CircS showed a significantly higher risk of frailty compared to those without CircS (Odds Ratio [OR] = 2.18, 95% Confidence Interval [CI]: 1.91-2.49, p < 0.001). A trend of increasing frailty risk with greater CircS component was observed (trend test p < 0.001). Age (p = 0.01) and race (p = 0.02) interactions notably influenced this association, although the direction of effect was consistent across subgroups. Sensitivity analysis further confirmed the strength of this relationship. CONCLUSION: This study identifies a strong positive correlation between CircS and frailty in the elderly. The risk of frailty escalates with an increasing number of CircS components. These findings highlight the intricate interplay between circadian syndrome and frailty in older adults, offering valuable insights for developing targeted prevention and intervention strategies.

The relationship between anxiety symptoms and disturbances in biological rhythms in patients with depression.

BACKGROUND: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments. METHODS: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet. RESULTS: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms. CONCLUSION: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety.

Circadian Disruption as a Risk Factor for Development of Cardiovascular and Metabolic Disorders - From Animal Models to Human Population.

The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.

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.

Guanxin V alleviates ventricular remodeling after acute myocardial infarction with circadian disruption by regulating mitochondrial dynamics.

PURPOSE: Circadian disruption has been a common issue due to modern lifestyles. Ventricular remodeling (VR) is a pivotal progressive pathologic change after acute myocardial infarction (AMI) and circadian disruption may have a negative influence on VR according to the latest research. Whether or not Guanxin V (GXV) has a positive effect on VR after AMI with circadian disruption drew our interest. METHODS: Rats were randomly divided into a sham group, an AMI group, an AMI with circadian disruption group, and an AMI with circadian disruption treated with the GXV group according to a random number table. RNA sequencing (RNA-Seq) was utilized to confirm the different expressed genes regulated by circadian disruption. Cardiac function, inflammation factors, pathological evaluation, and mitochondrial dynamics after the intervention were conducted to reveal the mechanism by which GXV regulated VR after AMI with circadian disruption. RESULTS: RNA-Seq demonstrated that NF-κB was up-regulated by circadian disruption in rats with AMI. Functional and pathological evaluation indicated that compared with the AMI group, circadian disruption was associcataed with deteriorated cardiac function, expanded infarcted size, and exacerbated fibrosis and cardiomyocyte apoptosis. Further investigation demonstrated that mitochondrial dynamics imbalance was induced by circadian disruption. GXV intervention reversed the inflammatory status including down-regulation of NF-κB. Reserved cardiac function, limited infarct size, and ameliorated fibrosis and apoptosis were also observed in the GXV treated group. GXV maintained mitochondrial fission/fusion imbalance through suppressed expression of mitochondrial fission-associated proteins. CONCLUSION: The study findings suggest that identified mitochondrial dysfunctions may underlie the link between circadian disruption and VR. GXV may exert cardioprotection after AMI with circadian disruption through regulating mitochondrial dynamics.

Circadian rhythm and disease: Relationship, new insights, and future perspectives.

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics. In this manuscript, we describe the circadian-related diseases so far investigated, and studies reporting relevant data on this topic, evidencing this relationship, are included. Despite the actual limitations in published work, there is clear evidence of the correlation between circadian rhythm dysregulation and disease origin/development, and, in this way, clock-related therapies emerge as great progress in the clinical field. Future improvements in such interventions can lead to the development of successful chronotherapy strategies, deeply contributing to enhanced therapeutic outcomes.

Beneficial effects of voluntary wheel running on activity rhythms, metabolic state, and affect in a diurnal model of circadian disruption.

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.

Strategies for circadian rhythm disturbances and related psychiatric disorders: a new cue based on plant polysaccharides and intestinal microbiota.

Circadian rhythm is essential to human physiological homeostasis and health. The oscillation of host circadian rhythm affects the composition and function of intestinal microbiota, meanwhile, the normal operation of host circadian rhythm depends on the diurnal changes of intestinal microbiota. The imbalance of intestinal micro-ecology or the disorder of host circadian rhythm may lead to psychiatric disorders, while the intervention of plant polysaccharides is a possible way to alleviate circadian rhythm disturbance and the related psychiatric diseases. This review discusses the interaction between host circadian rhythm and intestinal microbiota and their effects on psychiatric disorders, and proposes a possible strategy of plant polysaccharides to alleviate circadian rhythm disorders and related psychiatric disorders by regulating intestinal micro-ecology.

Night shift work and the risk of metabolic syndrome: Findings from an 8-year hospital cohort.

OBJECTIVES: Studies concerning the risk of metabolic syndrome associated with night work have shown inconsistent findings, due to imprecise working time data and cross-sectional design. We used register-based daily working time data to examine the risk of incident metabolic syndrome associated with night shift work. METHODS: Working time data collected between 2010 and 2018 of 5775 Taiwanese hospital workers were used to identify night shift workers and to calculate the number of night shifts. Metabolic syndrome was identified by annual occupational health examination results, which were linked to the working time data. Logistic regression models and generalized estimating equations were used to examine the association between night shift work and metabolic syndrome and the 5 components of metabolic syndrome. RESULTS: Night shift work is associated with a higher risk of developing metabolic syndrome (adjusted OR = 1.36, 95% CI = 1.04 to 1.78) and high waist circumference (adjusted OR = 1.27, 95% CI = 1.07 to 1.78) compared to day work. Among night shift workers, increased number of night shifts was associated with high blood pressure (adjusted OR = 1.15, 95% CI = 1.01 to 1.31). CONCLUSIONS: Night shift work is associated with metabolic risk factors. Long-term effects of circadian rhythm disruption on metabolic disturbances needs to be further studied.

Social Jetlag and Related Risks for Human Health: A Timely Review.

The term social jetlag is used to describe the discrepancy between biological time, determined by our internal body clock, and social times, mainly dictated by social obligations such as school or work. In industrialized countries, two-thirds of the studying/working population experiences social jetlag, often for several years. Described for the first time in 2006, a considerable effort has been put into understanding the effects of social jetlag on human physiopathology, yet our understanding of this phenomenon is still very limited. Due to its high prevalence, social jetlag is becoming a primary concern for public health. This review summarizes current knowledge regarding social jetlag, social jetlag associated behavior (e.g., unhealthy eating patterns) and related risks for human health.

Energy Balance and Control of Body Weight: Possible Effects of Meal Timing and Circadian Rhythm Dysregulation.

Conservation of the energy equilibrium can be considered a dynamic process and variations of one component (energy intake or energy expenditure) cause biological and/or behavioral compensatory changes in the other part of the system. The interplay between energy demand and caloric intake appears designed to guarantee an adequate food supply in variable life contexts. The circadian rhythm plays a major role in systemic homeostasis by acting as "timekeeper" of the human body, under the control of central and peripheral clocks that regulate many physiological functions such as sleep, hunger and body temperature. Clock-associated biological processes anticipate the daily demands imposed by the environment, being synchronized under ideal physiologic conditions. Factors that interfere with the expected demand, including daily distribution of macronutrients, physical activity and light exposure, may disrupt the physiologic harmony between predicted and actual behavior. Such a desynchronization may favor the development of a wide range of disease-related processes, including obesity and its comorbidities. Evidence has been provided that the main components of 24-h EE may be affected by disruption of the circadian rhythm. The sleep pattern, meal timing and meal composition could mediate these effects. An increased understanding of the crosstalk between disruption of the circadian rhythm and energy balance may shed light on the pathophysiologic mechanisms underlying weight gain, which may eventually lead to design effective strategies to fight the obesity pandemic.

Evidence for a dysfunction and disease-promoting role of the circadian clock in the diabetic retina.

Diabetic retinopathy is a major complication of chronic hyperglycemia and a leading cause of blindness in developed countries. In the present study the interaction between diabetes and retinal clocks was investigated in mice. It was seen that in the db/db mouse - a widely used animal model of diabetic retinopathy - clock function and circadian regulation of gene expression was disturbed in the retina. Remarkably, elimination of clock function by Bmal1-deficiency mitigates the progression of pathophysiology of the diabetic retina. Thus high-fat diet was seen to induce histopathology and molecular markers associated with diabetic retinopathy in wild type but not in Bmal1-deficient mice. The data of the present study suggest that Bmal1/the retinal clock system is both, a target and an effector of diabetes mellitus in the retina and hence represents a putative therapeutic target in the pathogenesis of diabetic retinopathy.

Early Life Stress and Chronobiological Rhythms Desynchronization: Possible Impact on Mood Symptoms and Suicidal Ideation in Bipolar Disorder.

ABSTRACT: The study aimed at investigating the potential impact of early stressful events on the clinical manifestations of bipolar disorder (BD). A sample of 162 adult individuals with BD was assessed using the Structural Clinical Interview for DSM-5, the Beck Depression Inventory-II, the Young Mania Rating Scale, the Early Trauma Inventory Self Report-Short Form, the Biological Rhythms Interview of Assessment in Neuropsychiatry, the Insomnia Severity Index, and the Scale for Suicide Ideation. A significant path coefficient indicated a direct effect of early life stressors on biological rhythms (coeff. = 0.26; p < 0.001) and of biological rhythms on depressive symptoms (coeff. = 0.5; p < 0.001), suicidal risk (coeff. = 0.3; p < 0.001), and insomnia (coeff. = 0.34; p < 0.001). Data suggested that the desynchronization of chronobiological rhythms might be one mediator of the association between early life stress and the severity of mood symptoms/suicidal ideation in BD. Addressing circadian rhythm alterations in subjects exposed to early stressors would help in preventing consequences of those stressors on BD.

Circadian Rhythm Sleep-Wake Disorders: a Contemporary Review of Neurobiology, Treatment, and Dysregulation in Neurodegenerative Disease.

Circadian rhythms oscillate throughout a 24-h period and impact many physiological processes and aspects of daily life, including feeding behaviors, regulation of the sleep-wake cycle, and metabolic homeostasis. Misalignment between the endogenous biological clock and exogenous light-dark cycle can cause significant distress and dysfunction, and treatment aims for resynchronization with the external clock and environment. This article begins with a brief historical context of progress in the understanding of circadian rhythms, and then provides an overview of circadian neurobiology and the endogenous molecular clock. Various tools used in the diagnosis of circadian rhythm sleep-wake disorders, including sleep diaries and actigraphy monitoring, are then discussed, as are the therapeutic applications of strategically timed light therapy, melatonin, and other behavioral and pharmacological therapies including the melatonin agonist tasimelteon. Management strategies towards each major human circadian sleep-wake rhythm disorder, as outlined in the current International Classification of Sleep Disorders - Third Edition, including jet lag and shift work disorders, delayed and advanced sleep-wake phase rhythm disorders, non-24-h sleep-wake rhythm disorder, and irregular sleep-wake rhythm disorder are summarized. Last, an overview of chronotherapies and the circadian dysregulation of neurodegenerative diseases is reviewed.