Rhythm Alterations Research Articles

Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mouse Hippocampus.

In mammals, the circadian system controls various physiological processes to maintain metabolism, behavior, and immune function during a daily 24 h cycle. Although driven by a cell-autonomous core clock in the hypothalamus, rhythmic activities are entrained to external cues, such as environmental lighting conditions. Exposure to artificial light at night (ALAN) can cause circadian disruption and thus is linked to an increased occurrence of civilization diseases in modern society. Moreover, alterations of circadian rhythms and dysregulation of immune responses, including inflammasome activation, are common attributes of neurodegenerative diseases, including Alzheimer', Parkinson's, and Huntington's disease. Although there is evidence that the inflammasome in the hippocampus is activated by stress, the direct effect of circadian disruption on inflammasome activation remains poorly understood. In the present study, we aimed to analyze whether exposure to constant light (LL) affects inflammasome activation in the mouse hippocampus. In addition to decreased circadian power and reduced locomotor activity, we found cleaved caspase 1 significantly elevated in the hippocampus of mice exposed to LL. However, we did not find hallmarks of inflammasome priming or cleavage of pro-interleukins. These findings suggest that acute circadian disruption leads to an assembled "ready to start" inflammasome, which may turn the brain more vulnerable to additional aversive stimuli.

24 h Rest/Activity Rhythms in Older Adults with Memory Impairment: Associations with Cognitive Performance and Depressive Symptomatology.

Little is known about links of circadian rhythm alterations with neuropsychiatric symptoms and cognition in memory impaired older adults. Associations of actigraphic rest/activity rhythms (RAR) with depressive symptoms and cognition are examined using function-on-scalar regression (FOSR). Forty-four older adults with memory impairment (mean: 76.84 ± 8.15 years; 40.9% female) completed 6.37 ± 0.93 days of actigraphy, the Beck depression inventory-II (BDI-II), mini-mental state examination (MMSE) and consortium to establish a registry for Alzheimer's disease (CERAD) delayed word recall. FOSR models with BDI-II, MMSE, or CERAD as individual predictors adjusted for demographics (Models A1-A3) and all three predictors and demographics (Model B). In Model B, higher BDI-II scores are associated with greater activity from 12:00-11:50 a.m., 2:10-5:50 p.m., 8:40-9:40 p.m., 11:20-12:00 a.m., higher CERAD scores with greater activity from 9:20-10:00 p.m., and higher MMSE scores with greater activity from 5:50-10:50 a.m. and 12:40-5:00 p.m. Greater depressive symptomatology is associated with greater activity in midafternoon, evening, and overnight into midday; better delayed recall with greater late evening activity; and higher global cognitive performance with greater morning and afternoon activity (Model B). Time-of-day specific RAR alterations may affect mood and cognitive performance in this population.

Circadian rhythm alterations affecting the pathology of neurodegenerative diseases.

The circadian rhythm is a nearly 24-h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple-system atrophy, focusing on research published in the last 3 years.

Non-steady state fluctuations in water levels exacerbate long-term and seasonal degradation of water quality in river-connected lakes

The hydrological regimes and environmental changes in large riverine lakes are known for their complexity and high level of uncertainty. Scientifically uncovering the response mechanisms of water environments under complex hydrological conditions has become a challenging research objective, in the interdisciplinary of environmental science and hydrology. This study delved into the unstable response process between water level and quality of Poyang Lake, the largest freshwater lake as well as one of the most intense hydrological variability water bodies in China. We developed a non-steady state identification approach incorporates Seasonal and Trend decomposition using Loess (STL) and Wavelet Correlation (WTC) methods. The results showed that there were remarkable alterations in the hydrological regime and water quality at both seasonal and long-term scale of Poyang Lake over the past nine years. These alterations were accompanied by significant non-steady state characteristics, reflecting the changes in the response between water level and quality. The employment of the STL-WTC method revealed a significant nonlinear response between the long-term trends of water level and quality, in both the 4-month and 12-month frequency bands. In particular, our findings showed an intriguing shift towards in-phase behavior between water level and quality in the 12-month frequency band, rather than the anti-phase pattern observed previously. This correlation changed more significantly in seasons where the fluctuation pattern of water level varied sharply, such as summer and winter in Poyang Lake. Our study underscored the hydrological conditions and water quality of large lakes connected to rivers do not exhibit a long-term stable unidirectional response state, alterations in hydrological rhythms may induce a transition in the relationship from negative correlation towards nonlinear positive correlation between water level and water quality. Finally, this non-steady state fluctuation of water conditions can further exacerbate long-term and seasonal degradation of water quality.

Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome.

Substance use disorders are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based quantitative proteomics, along with a data-independent acquisition analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveal cocaine and morphine differentially alter diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between the phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome. The proteomics data in this study are available via ProteomeXchange with identifier PXD042043.

Abstract A048: The importance of time: Circadian rhythm disruption and prostate cancer

Abstract Circadian rhythms are evolutionarily created cycles programmed to integrate human behavior, physiology, and metabolism with the surrounding environment. The core clock machinery is composed of an autoregulatory network. The positive components of the loop are CLOCK and BMAL transcription factors, which heterodimerize to regulate expression of key circadian genes through E-box elements. CLOCK/BMAL regulate expression of cryptochrome (CRY1 and CRY2) and period (PER1, PER2, and PER3) genes, which are the negative components of the circadian loop. CRYs and PERs repress CLOCK/BMAL activity, thus conferring daily rhythmicity of cellular, metabolic, and physiological functions for homeostatic maintenance. Disruption to these rhythms, via nighttime light exposure or other forms of desynchronization, has been linked to poor health outcomes. Specifically, circadian disruption is designated as a probable carcinogen by the World Health Organization. Subsequent epidemiology research identified pilots and other shift workers have an increased risk of prostate cancer (PCa). Additional genomic studies identified multiple core clock genes (CCGs) with associated upregulation and/or downregulation in prostatic tumor tissues compared to benign samples. CCGs have also been found to impact several key oncogenic pathways including cell cycle control, apoptosis, DNA repair, and metabolic regulation. In order to further clarify the risk of an altered circadian genome, we analyzed multiple publicly available human PCa datasets to identify clinical correlates in both primary and metastatic disease. Intriguingly, we found genomic alterations in circadian rhythm were associated with increased Gleason score, cancer staging, and positive node status in primary disease. Furthermore, within a subset of patients with castrate-resistant prostate cancer (CRPC), those with concurrent altered CCGs had a decreased survival compared to patients without altered CCGs. This data further emphasizes the importance of circadian rhythm consideration in the context of malignancy and preventative medicine. With so many unknown questions and a high potential to identify subtypes of tumors with altered CCGs and aggressive disease, future studies are needed to improve therapeutic efficacy. Analysis of circadian genomic alterations with subsequent comparison of demographics including ethnicity, occupation, and sleep habits would expand the understanding of everyday variables on circadian disruption. Additionally, the comparison of short-term versus long-term circadian synchronizations should be analyzed to identify higher-risk populations. Lastly, the long-term goal should be to discover potential circadian targeted treatments or to identify ways of involvement of circadian rhythmicity in cancer treatment, including chronotherapy (i.e., time of day of treatment) to optimize the impact of cancer therapeutics to enhance patient outcome. Citation Format: Sierra T. Pence, Ayesha A. Shafi. The importance of time: Circadian rhythm disruption and prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A048.

Periodic and Aperiodic EEG Features as Potential Markers of Developmental Dyslexia.

Developmental Dyslexia (DD) is a neurobiological condition affecting the ability to read fluently and/or accurately. Analyzing resting-state electroencephalographic (EEG) activity in DD may provide a deeper characterization of the underlying pathophysiology and possible biomarkers. So far, studies investigating resting-state activity in DD provided limited evidence and did not consider the aperiodic component of the power spectrum. In the present study, adults with (n = 26) and without DD (n = 31) underwent a reading skills assessment and resting-state EEG to investigate potential alterations in aperiodic activity, their impact on the periodic counterpart and reading performance. In parieto-occipital channels, DD participants showed a significantly different aperiodic activity as indexed by a flatter and lower power spectrum. These aperiodic measures were significantly related to text reading time, suggesting a link with individual differences in reading difficulties. In the beta band, the DD group showed significantly decreased aperiodic-adjusted power compared to typical readers, which was significantly correlated to word reading accuracy. Overall, here we provide evidence showing alterations of the endogenous aperiodic activity in DD participants consistently with the increased neural noise hypothesis. In addition, we confirm alterations of endogenous beta rhythms, which are discussed in terms of their potential link with magnocellular-dorsal stream deficit.

1027 Title: Hypersomnolence following resection of a craniopharyngioma

Abstract Introduction Craniopharyngiomas are rare tumors that arise from Rathke’s pouch remnants along the pituitary-hypothalamic axis. The tumor and its treatment can lead to significant neurological and endocrinological complications including alterations in appetite, endocrine insufficiency, circadian rhythms and sleep. We report the case of a woman who developed hypersomnia following resection of a craniopharyngioma Report of case(s) This 38-year-old female with neither significant past medical history of sleep, medical, neurological, or psychiatric disorders nor a family history of narcolepsy presented with galactorrhea and amenorrhea. Imaging showed a pituitary tumor. She underwent resection of the tumor with a tissue diagnosis of an adamantinomatous craniopharyngioma. MRI post procedure showed post-surgical changes without new lesions. Diabetes insipidus and panhypopituitarism developed for which appropriate replacement therapy was initiated. She gained approximately one hundred pounds in the weeks post-surgery. Her family described new onset snoring in supine sleeping position and witnessed apneas. She denied hypnagogic hallucinations, cataplexy, or sleep paralysis. She presented to the sleep medicine clinic a few months later for evaluation of persistent hypersomnolence. Conclusion The most common sleep disorders post craniopharyngioma resection are sleep-related breathing disorder, hypersomnia, and circadian rhythm disorder. Sleep and appetite are felt to be altered because of direct surgical compression, injury or vascular compromise of structures involved in the control of sleep, wakefulness, and appetite. This can produce hypothalamic dysfunction induced obesity with secondary sleep-related breathing disorder and worsening hypersomnolence. In this woman the temporal relationship between the surgery and the onset of symptoms is most suggestive of this hypothalamic injury, resulting in abnormal regulation of both appetite and sleep. Improvements in weight control and hypersomnia with use of stimulant therapy in the setting of secondary obstructive sleep apnea have been reported and in addition to standard positive airway pressure therapies give hope for the management of these complications of craniopharyngioma resection. Support (if any)

0251 Sex differences in the associations of childhood obesity with sleep characteristics, access to screens, and nocturnal melatonin

Abstract Introduction Insufficient sleep and circadian rhythm alterations are associated with metabolic disorders including obesity, with increasing evidence that these associations can emerge in childhood. In parallel, screen media access in the bedroom at night has negative effects on circadian rhythms, sleep, and other behaviors, which can contribute to obesity development. In the current work, we analyzed the associations of childhood obesity with self-reported sleep characteristics, access to screens in the bedroom, and nocturnal melatonin, considering potential sex differences. Methods The study cohort is composed of 244 children 7-16 years old, among which 140 have a body mass index z-scores >2, characterized as obesity according to world health organization criteria. There are 124 girls (11.21 ± 2.42 years) and 120 boys (11.19 ± 2.22 years). Melatonin was measured through immunoassay in saliva samples, which were collected at three time points of the evening of a school day: 4h before sleep, 2h before sleep, and 1h after sleep start. The chronotype score was obtained using the Horne and Ostberg questionnaire. Participants reported the number of screens present in the bedroom at night, and their bedtimes and wakeup times during both weekdays and weekend. The sleep disturbance scale for children and an abbreviated pediatric sleep questionnaire about sleep apnea symptoms were completed by a parent. Results BMI z-scores were significantly correlated with more parent-reported sleep disturbances (p< 0.01), higher sleep apnea scores (p< 0.01), shorter sleep duration during weekdays (p< 0.01), and the number of screens in the bedroom (p=0.05) in boys but not in girls (p=0.52, p=0.15, p=0.83, and p=0.37). On the other hand, BMI z-scores were significantly correlated with melatonin level at +1h after sleep onset (p=0.05) in girls but not in boys (p=0.96). No significant correlations were observed between the BMI z-score and the pre-sleep melatonin measures. Conclusion According to our findings, there is some differentiation by sex in relationships between body weight and various sleep and circadian measures. Specifically, in boys, obesity was associated with shorter and disturbed sleep with more sleep apnea, whereas in girls, obesity was linked with lowered nocturnal melatonin expression. Support (if any)

Tackling Insomnia Symptoms through Vestibular Stimulation in Patients with Breast Cancer: A Perspective Paper.

Insomnia symptoms are common among patients with breast cancer (BC; 20-70%) and are predictors of cancer progression and quality of life. Studies have highlighted sleep structure modifications, including increased awakenings and reduced sleep efficiency and total sleep time. Such modifications may result from circadian rhythm alterations consistently reported in this pathology and known as carcinogenic factors, including lower melatonin levels, a flattened diurnal cortisol pattern, and lower rest-activity rhythm amplitude and robustness. Cognitive behavioral therapy and physical activity are the most commonly used non-pharmacological interventions to counter insomnia difficulties in patients with BC. However, their effects on sleep structure remain unclear. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms. Indeed, recent reports have shown that vestibular stimulation could resynchronize circadian rhythms and improve deep sleep in healthy volunteers. Moreover, vestibular dysfunction has been reported following chemotherapy. This perspective paper aims to support the evidence of using galvanic vestibular stimulation to resynchronize circadian rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival.

Differential sensitivity to speech rhythms in young and older adults.

Sensitivity to the temporal properties of auditory patterns tends to be poorer in older listeners, and this has been hypothesized to be one factor contributing to their poorer speech understanding. This study examined sensitivity to speech rhythms in young and older normal-hearing subjects, using a task designed to measure the effect of speech rhythmic context on the detection of changes in the timing of word onsets in spoken sentences. A temporal-shift detection paradigm was used in which listeners were presented with an intact sentence followed by two versions of the sentence in which a portion of speech was replaced with a silent gap: one with correct gap timing (the same duration as the missing speech) and one with altered gap timing (shorter or longer than the duration of the missing speech), resulting in an early or late resumption of the sentence after the gap. The sentences were presented with either an intact rhythm or an altered rhythm preceding the silent gap. Listeners judged which sentence had the altered gap timing, and thresholds for the detection of deviations from the correct timing were calculated separately for shortened and lengthened gaps. Both young and older listeners demonstrated lower thresholds in the intact rhythm condition than in the altered rhythm conditions. However, shortened gaps led to lower thresholds than lengthened gaps for the young listeners, while older listeners were not sensitive to the direction of the change in timing. These results show that both young and older listeners rely on speech rhythms to generate temporal expectancies for upcoming speech events. However, the absence of lower thresholds for shortened gaps among the older listeners indicates a change in speech-timing expectancies with age. A further examination of individual differences within the older group revealed that those with better rhythm-discrimination abilities (from a separate study) tended to show the same heightened sensitivity to early events observed with the young listeners.

Evolving Eocene–Miocene seasonality decoded from aragonitic laminae deposited within the Qaidam Basin, North Tibetan Plateau

A thorough understanding of sub-decadal paleoclimate variability typically depends on ultra-precise geochronological constraints that are rarely obtained. While the seasonally resolved nature of varved successions enlarges the opportunity, their identification beyond Quaternary ages is difficult; thus is frequently met with skepticism. The Cenozoic strata in the Qaidam Basin, for instance, feature expanded rhythmite successions, whereas the periodicity of these laminae remains to be explored. Targeting Eocene- (VE; ∼42.0 Ma), Oligocene- (VO; ∼26.9 Ma) and Miocene-aged (VM; ∼19.5 Ma) intervals, herein we report layer-based petrographic observations coupled with mineralogical and phase-specific geochemical analyses of millimeter-scale rhythmic alterations between yellowish- and grayish-colored aragonitic layers. Noting a constant δ13Ccarb offset (∼ 2.8‰) between yellowish- and grayish-colored laminae, these isotope data imply seasonally paced alternations between microbial induction and inorganic carbonate precipitation. In addition, covariations between inorganic oxygen isotope (δ18Ocarb) and elemental ratios (e.g., Mn/Fecarb, Sr/Basilic and Chemical Index of Alteration, CIAsilic) reveal evolving seasonality, capturing Eocene–Oligocene aridification followed by an early Miocene reversal. Therefore, the varved fill of the Qaidam Basin serves as an annually resolved, and as yet under-explored, archive of evolving Cenozoic paleoseasonality in the aftermath of the Indo–Asia collision.

Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy

ObjectiveTo determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. MethodsA prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. ResultsTwenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). ConclusionThe results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Effect of Ketamine on Sleep in Treatment-Resistant Depression: A Systematic Review.

Depression is a debilitating disease with a high socioeconomic burden. Regular antidepressants usually require several weeks to ameliorate symptoms; however, numerous patients do not achieve remission. What is more, sleep disturbances are one of the most common residual symptoms. Ketamine is a novel antidepressant with rapid onset of action with a proven antisuicidal effect. Little is known about its impact on sleep-wake and circadian rhythm alterations. The aim of this systematic review is to research the impact ketamine has on sleep disturbances in depression. PubMed, Web of Science, and APA PsycINFO were searched for relevant studies on ketamine's impact on sleep disturbances in depression. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA2020 methodology was applied. The systematic review protocol was registered in the PROSPERO Registry (CRD42023387897). Five studies were included in this review. Two studies reported significant improvement in sleep measured by MADRS (Montgomery-Åsberg Depression Rating Scale) and QIDS-SR16 (Quick Inventory of Depressive Symptomatology Self-Report (16-item)) scales after intravenous ketamine and intranasal esketamine administration. One case report showed mitigation of symptoms in PSQI (Pittsburgh Sleep Quality Index) and ISI (Insomnia Severity Index) during 3-month treatment with esketamine. In two studies, sleep was objectively measured by nocturnal EEG (electroencephalography) and showed a decrease in nocturnal wakefulness accompanied by an increase in slow wave (SWS) and rapid eye movement (REM) sleep. Ketamine reduces the severity of sleep insomnia in depression. Robust data are lacking. More research is needed.

Circadian variation in hematotoxicity of the antineoplastic agent “5 Fluorouracil (5 FU)” in female rats and its relevance to chronotherapy

ABSTRACT 5-Fluorouracil (5-FU) is an antineoplastic drug. Although 5-FU is effective in targeting cancer cells, it also affects healthy cells, which can lead to clear haematological toxicity. The present study aimed to determine whether the haematological toxicity of 5-FU varies over a 24-hour period. Female rats were synchronised to a 12/12 light-dark (L/D) cycle. Rats were injected with 300 mg/kg 5-FU at six different circadian stages (1, 5, 9, 13, 17, 21 Zeitgebers (ZT)). The maximum rhythmic alteration was observed when 5-FU was administered at 5-ZT, while the minimum was observed at 21-ZT. These results suggest that the haematological toxicity of 5-FU is maximal when administered in the middle of the light-rest phase, while the haematological tolerance is optimal when 5-FU is administered at the end of the dark phase in rats, which corresponds to the end of the daytime activity phase in human patients.

Electro-Mechanical Alterations in Atrial Fibrillation: Structural, Electrical, and Functional Correlates.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice affecting both patients' survival and well-being. Apart from aging, many cardiovascular risk factors may cause structural remodeling of the atrial myocardium leading to atrial fibrillation development. Structural remodelling refers to the development of atrial fibrosis, as well as to alterations in atrial size and cellular ultrastructure. The latter includes myolysis, the development of glycogen accumulation, altered Connexin expression, subcellular changes, and sinus rhythm alterations. The structural remodeling of the atrial myocardium is commonly associated with the presence of interatrial block. On the other hand, prolongation of the interatrial conduction time is encountered when atrial pressure is acutely increased. Electrical correlates of conduction disturbances include alterations in P wave parameters, such as partial or advanced interatrial block, alterations in P wave axis, voltage, area, morphology, or abnormal electrophysiological characteristics, such as alterations in bipolar or unipolar voltage mapping, electrogram fractionation, endo-epicardial asynchrony of the atrial wall, or slower cardiac conduction velocity. Functional correlates of conduction disturbances may incorporate alterations in left atrial diameter, volume, or strain. Echocardiography or cardiac magnetic resonance imaging (MRI) is commonly used to assess these parameters. Finally, the echocardiography-derived total atrial conduction time (PA-TDI duration) may reflect both atrial electrical and structural alterations.

The psychophysiology of guilt in healthy adults

Guilt is a negative emotion, elicited by realizing one has caused actual or perceived harm to another person. Anecdotally, guilt often is described as a visceral and physical experience. However, while the way that the body responds to and contributes to emotions is well known in basic emotions, little is known about the characteristics of guilt as generated by the autonomic nervous system. This study investigated the physiologic signature associated with guilt in adults with no history of psychological or autonomic disorder. Healthy adults completed a novel task, including an initial questionnaire about their habits and attitudes, followed by videos designed to elicit guilt, as well as the comparison emotions of amusement, disgust, sadness, pride, and neutral. During the video task, participants’ swallowing rate, electrodermal activity, heart rate, respiration rate, and gastric activity rate were continuously recorded. Guilt was associated with alterations in gastric rhythms, electrodermal activity, and swallowing rate relative to some or all the comparison emotions. These findings suggest that there is a mixed pattern of sympathetic and parasympathetic activation during the experience of guilt. These results highlight potential therapeutic targets for modulation of guilt in neurologic and psychiatric disorders with deficient or elevated levels of guilt, such as frontotemporal dementia, posttraumatic stress disorder, and Obsessive-compulsive disorder.

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.

Circadian rhythm-related genes index: A predictor for HNSCC prognosis, immunotherapy efficacy, and chemosensitivity.

Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck cancer and is highly aggressive and heterogeneous, leading to variable prognosis and immunotherapy outcomes. Circadian rhythm alterations in tumourigenesis are of equal importance to genetic factors and several biologic clock genes are considered to be prognostic biomarkers for various cancers. The aim of this study was to establish reliable markers based on biologic clock genes, thus providing a new perspective for assessing immunotherapy response and prognosis in patients with HNSCC. We used 502 HNSCC samples and 44 normal samples from the TCGA-HNSCC dataset as the training set. 97 samples from GSE41613 were used as an external validation set. Prognostic characteristics of circadian rhythm-related genes (CRRGs) were established by Lasso, random forest and stepwise multifactorial Cox. Multivariate analysis revealed that CRRGs characteristics were independent predictors of HNSCC, with patients in the high-risk group having a worse prognosis than those in the low-risk group. The relevance of CRRGs to the immune microenvironment and immunotherapy was assessed by an integrated algorithm. 6-CRRGs were considered to be strongly associated with HNSCC prognosis and a good predictor of HNSCC. The riskscore established by the 6-CRRG was found to be an independent prognostic factor for HNSCC in multifactorial analysis, with patients in the low-risk group having a higher overall survival (OS) than the high-risk group. Nomogram prediction maps constructed from clinical characteristics and riskscore had good prognostic power. Patients in the low-risk group had higher levels of immune infiltration and immune checkpoint expression and were more likely to benefit from immunotherapy. 6-CRRGs play a key predictive role for the prognosis of HNSCC patients and can guide physicians in selecting potential responders to prioritise immunotherapy, which could facilitate further research in precision immuno-oncology.

Sleep disturbance in schizophrenia spectrum disorders: more than just a symptom?

Sleep disturbance is commonly reported in patients with schizophrenia spectrum disorder (SSD) in the clinical setting. Sleep features can be assessed subjectively, with self-report sleep questionnaires, and objectively with actigraphy and electroencephalogram recordings. Traditionally, electroencephalogram studies have focused on sleep architecture. More recently, numerous studies have investigated alterations in sleep-specific rhythms, including electroencephalogram oscillations, such as sleep spindles and slow waves, in patients with SSD compared with control subjects. Here, I briefly discuss how sleep disturbance is highly prevalent in patients with SSD and I present findings from studies demonstrating abnormalities in sleep architecture and sleep-oscillatory rhythms, with an emphasis on sleep spindles and slow-wave deficits, in these patients. This increasing body of evidence highlights the importance of sleep disturbance in SSD and points to several future research directions with related clinical implications, thus showing that sleep disturbance is more than just a symptom in these patients.