Littérature scientifique sur le sujet « Rest-activity circadian rhythms »

Circadian rhythms, which respond to the day-night cycle on the earth, arise from the endogenous timekeeping system within organisms, called the “biological clock.” For accurate circadian rhythms, daily fluctuations in light and temperature are considered one of the important time cues. In social insects, both abiotic and biotic factors (i.e., social interactions) play a significant role in activity-rest rhythm regulation. However, it is challenging to monitor individual activity-rest rhythms in a colony because of the large group size and small body size. Therefore, it is unclear whether individuals in a colony exhibit activity-rest rhythms and how social interactions regulate their activity-rest rhythms in the colony. This study developed an image-based tracking system using 2D barcodes for Diacamma cf. indicum from Japan (a monomorphic ant) and measured the locomotor activities of all colony members under laboratory colony conditions. We also investigated the effect of broods on activity-rest rhythms by removing all broods under colony conditions. Activity-rest rhythms appeared only in isolated ants, not under colony conditions. In addition, workers showed arrhythmic activities after brood removal. These results suggested that a mixture of social interactions, and not light and temperature, induces the loss of activity-rest rhythms. These results contribute to the knowledge of a diverse pattern of circadian activity rhythms in social insects.

<b>Background:</b> Little is known about sleep and circadian rhythms in survivors of acute respiratory failure (ARF) after hospital discharge. <b>Objectives:</b> To examine sleep and rest-activity circadian rhythms in ARF survivors 3 months after hospital discharge, and to compare them with a community-dwelling population. <b>Methods:</b> Sleep diary, actigraphy data, and insomnia symptoms were collected in a pilot study of 14 ARF survivors. Rest-activity circadian rhythms were assessed with wrist actigraphy and sleep diary for 9 days, and were analyzed by cosinor and non-parametric circadian rhythm analysis. <b>Results:</b> All participants had remarkable actigraphic sleep fragmentation, 71.5% had subclinical or clinical insomnia symptoms. Compared to community-dwelling adults, this cohort had less stable rest-activity circadian rhythms (<i>p</i> < 0.001), and weaker circadian strength (<i>p</i> < 0.001). <b>Conclusion:</b> Insomnia and circadian disruption were common in ARF survivors. Sleep improvement and circadian rhythm regularity may be a promising approach to improve quality of life and daytime function after ARF.

Objective: Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. Methods: A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. Results: Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). Conclusions: Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.

Background General anesthesia is commonly associated with sleep disorders, fatigue, drowsiness, and mood alterations in patients. The authors examined whether general (propofol) anesthesia can impact the circadian temporal structure by disturbing circadian rest-activity and body temperature rhythms under normal light-dark conditions (light-dark 12:12 h) in rats. Methods A group of rats was anesthetized with propofol, and another was injected with 10% Intralipid, which was used as a control lipidic solution. The authors examined six groups of rats according to the Zeitgeber time of intraperitoneal administration (ZT6, ZT10, ZT16) and the substance injected (propofol or Intralipid). Results On the day after anesthesia, propofol induced a significant 60- to 80-min phase advance of both rest-activity and body temperature rhythms. A significant 45- to 60-min phase advance of body temperature and a significant 20-min phase advance of rest-activity were still observed on the second day after anesthesia. The amplitudes of both rest-activity and body temperature rhythms were decreased on the first and second days after anesthesia. The 24-h mean rest-activity rhythm was decreased on the day after anesthesia, whereas the 24-h mean body temperature rhythm was not modified. Conclusion The results demonstrate the disturbing effects of propofol anesthesia on the circadian time structure in rats under normal light conditions.

We want to study the circadian rhythm of dROMs and anti-oxidative power in dairy cattle during dry period and the possible involvement of the circadian organization of rest/activity cycles in the fluctuation of redox state. For this purpose we recorded TLA in five clinically healthy Bruna Italian dairy cattle by means of an actigraphy-based data logger, Actiwatch-Mini<sup>®</sup>. Blood samples were collected every 3 hours over a 48-hour period for the assessment of free radicals (dROMs) and the antioxidant power: antioxidant barrier (Oxy-ads) and thiol-antioxidant barrier (SHp). All animals were in the same productive period (dry) and they were housed in the same stable under natural photoperiod and ambient temperature. One-way repeated measure ANOVA was used to determine a statistical significant effect of time on the studied parameters. A trigonometric statistical model was applied to characterize the main rhythmic parameters according to the single cosinor procedure. A significant effect of time on all studied parameters was observed. They showed a diurnal acrophase and different degrees of robustness of rhythms. In conclusion, we can claim that there is a synergism between the dROM circadian rhythm and the circadian rhythm of anti-oxidative power. These rhythms do not have any implication for the issue of causation with the TLA circadian rhythms.

Shift work schedules, intensive physical exercise late in the day, psychological stress, or a busy lifestyle might induce disorders of the circadian structure, which can affect health on both the physiological and neurobehavioral levels. Rest–activity rhythm is strongly connected with an organism’s circadian structure, and irregular sleep–wake patterns can lead to a disruption of entrainment, resulting in physiological and neurobehavioral dysfunction. Shift nurses are often subject to disturbances in the quality and duration of their sleep, raising the possibility of negative impacts on their health and their patients' safety. Researchers have used actigraphy in a number of studies to assess sleep patterns. Because of the close connection between sleep and circadian structure, it may be useful to extend the evaluation of actigraphy data to the analysis of the rest–activity rhythm with rhythmometric procedures to provide a better understanding of possible sleep disorders in relation to entrainment. Actigraphy is an easy and reliable way to study these rhythms and identify possible circadian-rhythm disorders. In this article, the authors discuss methodological issues concerning the evaluation of the rest–activity rhythm, with a focus on actigraphy.

In an attempt to force internal desynchronization between the rest-activity rhythm and the body temperature rhythm of the squirrel monkey (Saimiri sciureus), five animals were studied in a 14:14 light-dark cycle. In four animals a 28-h spectral component was found to predominate in the rest-activity rhythm, whereas an unentrained circadian component (tau = 25.9 +/- 0.4 h) predominated in the body temperature rhythm. Plots of the cycle-by-cycle acrophases of the two rhythms confirm that they desynchronize, due to the failure of the temperature rhythm to entrain to the light-dark cycle. These data from intact animals provide further support for the hypothesis that the squirrel monkey circadian timing system has at least two pacemakers. A rhythm for which the supra-chiasmatic nuclei (SCN) have previously been shown to be essential (rest-activity) simultaneously exhibited a different period from a rhythm (body temperature) that has been shown to persist after destruction of the SCN.

Abstract Introduction Disrupted circadian rest-activity rhythms in older adults have been associated with an increased risk of cognitive decline and mortality. While light is one of the most potent synchronizing agents for the human circadian system, little is known about how light may influence rest-activity rhythms in older adults. We aimed to investigate the relationship between the amount of light exposure and rest-activity rhythm parameters using actigraphy data from a large cohort study. Methods 553 community-dwelling older adults (aged 72±5, 142 (25.5%) female) from the Chicago Healthy Aging Study cohort underwent recording of activity and ambient light exposure for a minimum of five 24-hour periods, using Actiwatch-L (Phillips Respironics). The average recording duration was 6.7±0.5 days. An extension to the traditional cosine model was used to compute circadian rest-activity rhythm parameters, including the amplitude (a measure of strength), the goodness of fit (pseudo F statistic; a measure of robustness), and acrophase (timing of peak activity). Light exposure was measured by time spent above light thresholds of 100, 200, 500, and 1000 lux per day (TAT100, TAT200, TAT500, TAT1000, respectively). Bivariate associations between rhythm parameters and TAT values were examined with Spearman’s correlation coefficients. Variables that met a significant threshold (p<0.05) were entered into multivariable models to adjust for potential confounders including age, sex, race, and season. Results Robustness of the rest-activity rhythm, measured by extended cosine pseudo-F statistics, was associated with TAT100 (partial Spearman’s correlation coefficient 0.12, p=0.008), TAT200 (coefficient 0.13, p=0.03), TAT500 (coefficient 0.16, p<0.001), and TAT 1000 (coefficient 0.18, p<0.001). TAT100/200/500/1000 were also associated with the strength of the rest-activity rhythm, measured by amplitude of the extended cosine fit (partial Spearman’s correlation coefficient vs. TAT100: 0.12, p=0.006, TAT200: 0.14, p=0.002, TAT500: 0.16, p<0.001, TAT1000: 0.18, p<0.001), after adjusting for age, sex, race, and season. Conclusion Across the seasons, greater daily light exposure is associated with more robust circadian rest-activity rhythm in community-dwelling older adults. Whether the enhancement of light exposure can improve the strength and robustness of rest-activity rhythm needs to be tested with future intervention studies. Support (if any):

Objective Data processing in analysis of circadian rhythm was performed in various ways. However, there was a lack of evidence for the optimal analysis of circadian rest-activity rhythm. Therefore, we aimed to perform mathematical simulations of data processing to investigate proper evidence for the optimal analysis of circadian rest-activity rhythm.Methods Locomotor activities of 20 ICR male mice were measured by infrared motion detectors. The data of locomotor activities was processed using data summation, data average, and data moving average methods for cosinor analysis. Circadian indices were estimated according to time block, respectively. Also, statistical F and p-values were calculated by zero-amplitude test.Results The data moving average result showed well-fitted cosine curves independent of data processing time. Meanwhile, the amplitude, MESOR, and acrophase were properly estimated within 800 seconds in data summation and data average methods.Conclusion These findings suggest that data moving average would be an optimal method for data processing in a cosinor analysis and data average within 800-second data processing time might be adaptable. The results of this study can be helpful to analyze circadian restactivity rhythms and integrate the results of the studies using different data processing methods.

Circadian rhythms are approximately 24 h cycles in physiology and behaviour that enable organisms to anticipate predictable rhythmic changes in their environment. These rhythms are a hallmark of normal healthy physiology, and disruption of circadian rhythms has implications for cognitive, metabolic, cardiovascular and immune function. Circadian disruption is of increasing concern, and may occur as a result of the pressures of our modern 24/7 society—including artificial light exposure, shift-work and jet-lag. In addition, circadian disruption is a common comorbidity in many different conditions, ranging from aging to neurological disorders. A key feature of circadian disruption is the breakdown of robust, reproducible rhythms with increasing fragmentation between activity and rest. Circadian researchers have developed a range of methods for estimating the period of time series, typically based upon periodogram analysis. However, the methods used to quantify circadian disruption across the literature are not consistent. Here we describe a range of different measures that have been used to measure circadian disruption, with a particular focus on laboratory rodent data. These methods include periodogram power, variability in activity onset, light phase activity, activity bouts, interdaily stability, intradaily variability and relative amplitude. The strengths and limitations of these methods are described, as well as their normal ranges and interrelationships. Whilst there is an increasing appreciation of circadian disruption as both a risk to health and a potential therapeutic target, greater consistency in the quantification of disrupted rhythms is needed.

Les mécanismes moléculaires contrôlant les rythmes circadiens sont conservés parmi les organismes des différents règnes (plantes, animaux et champignons). Ils se composent de boucles de rétroaction où un complexe d’activation transcriptionnelle, l’hétérodimère CLK/CYC chez la drosophile, entraîne l'expression des répresseurs de son activité, les gènes et protéines PER et TIM chez la mouche. De manière importante, la période de l'oscillateur dépend en grande partie par des mécanismes post-transcriptionnels qui régulent l’accumulation et l'activité des composantes positifs et négatifs de la boucle. Bien que de nombreux partenaires d'interaction modifiant les composants d'horloge de base ont déjà pu être isolés, le schéma reste encore incomplet. Dans le cadre de la recherche de nouveaux composants de cette horloge, nous avons réalisé un crible comportemental basé sur l'expression ciblée de transgènes ARNi dirigés contre la moitié du génome de Drosophila melanogaster. Cinquante-quatre nouveaux gènes putatifs ont pu être identifiés. Au cours de ce travail, j'ai étudié le rôle de deux d’entre eux, sélectionnés pour les forts défauts comportementaux de l'expression de leur transgène ARNi. Le gène CG12082 de la drosophile est l’orthologue de l’Ubiquitin-specific protéase 5 (USP5) chez l’homme. La dérégulation d’Usp5 retarde les oscillations de la protéine PER dans les neurones d'horloge et allonge la période d'activité locomotrice des mouches. Chez les mouches ARNi Usp5, des formes à haut poids moléculaire des protéines PER et TIM s'accumulent pendant le matin, alors qu’elles sont normalement dégradées chez les contrôles. On a pu montrer que Usp5 participe directement à la dégradation de la protéine PER, indépendamment de TIM. En accord avec le rôle décrit pour l’orthologue humaine, Usp5 serait susceptible de contrôler la dégradation des protéines par son activité de démontage des chaînes libres de polyubiquitine présents dans la cellule, qui peuvent entrer en compétition avec les protéines ubiquitinylées pour la reconnaissance au niveau du protéasome, bloquant leur dégradation. La majorité des travaux ont porté sur un gène isolé au cours de notre crible, Strip, dont les fonctions étaient encore inconnues. Strip interagit avec Cka, une nouvelle sous-unité régulatrice de l’enzyme phosphatase PP2A. La dérégulation à la fois de Strip et/ou de Cka amène à des phénotypes comportementaux de période longue. D’un point de vue moléculaire, des formes hyper-phosphorylées de la protéine CLK s’accumulent dans la matinée quand Cka et/ou Strip sont perturbées. La dérégulation des activités générales de PP2A produit également une hyper-phosphorylation de CLK le matin, indiquant que, grâce à Cka/Strip, les complexes PP2A contrôlent la déphosphorylation de CLK à la fin du cycle. Il est connu que les formes hyper-phosphorylés de CLK sont transcriptionnellement inactives. En effet, la transcription des gènes tim et vrille, cibles de CLK, est fortement réduite dans les mouches ARNi Cka. En plus de PP2A/Cka, des complexes PP2A contenant une autre sous-unité régulatrice, Wdb, ont été montré pour déstabiliser CLK en culture des cellules (Kim et Edery, 2006). Nous montrons que la dérégulation de Wdb affecte la stabilité du CLK également dans la mouche adulte, sans toutefois induire aucun effet apparent sur sa phosphorylation. En conclusion, deux complexes PP2A différents agissent sur la protéine CLK : le complexe PP2A/Cka/Strip contrôle la déphosphorylation de CLK et sa réactivation, tandis que PP2A/Wdb affecte la stabilité de CLK indépendamment ou après PP2A/Cka. Ces résultats enrichissent l’étude de la régulation post-traductionnelle de la protéine CLK, qui était largement mal connue.Pour conclure, cette étude a permis de décrire deux nouveaux composants de la boucle moléculaire qui contrôle les rythmes circadiens chez la mouche du vinaigre, Drosophila melanogaster<br>The molecular mechanism underlying circadian rhythms is conserved among organisms and consists of feedback loops where a transcriptional activating complex (the CLOCK (CLK)/CYCLE (CYC) heterodimer in Drosophila) drives the expression of the repressors of its activity (the period (per) and timeless (tim) genes and proteins in Drosophila). Importantly, the pace of the oscillator largely depends on post-transcriptional mechanisms that regulate the accumulation and activity of both the positive and negative components of the loop. A number of interacting partners that modify core clock components have already been isolated, but more are expected. Looking for new clock components, we set up a behavioral screen based on targeted expression of RNAi transgenes directed to half of the Drosophila genome. 54 putative new clock genes have been identified. Among them, some were independently reported to function within the fruit fly molecular clock, thus validating the screen. In this work, I investigated the circadian role of additional “positive” genes, selected for the strong behavioral defect induced by the expression of the corresponding RNAi. The CG12082 gene codes for the fruit fly ortholog of the human Ubiquitin-specific protease 5 (USP5). Downregulation of USP5 in clock cells lengthens the period of locomotor activity of flies as well as PER protein oscillations in clock neurons. High molecular weight forms of PER and TIM proteins accumulate during the morning after USP5 knockdown, while these forms are degraded in controls. In addition, TIM is not stabilized in the absence of PER, while PER still accumulate in the absence of TIM. Therefore, USP5 directly participates in the degradation of the PER protein and, later, of the TIM protein at the end of the cycle. Being a deubiquitinylase enzyme, USP5 may directly deubiquitinate PER. However, accordingly to the role described for the human ortholog, USP5 likely controls protein degradation through the disassembling of the unanchored polyubiquitin chains present in the cell that could compete with ubiquitinated-PER for proteasome recognition and subsequent breakdown.The majority of the work has focused on an unknown gene isolated in the screen, that, accordingly to the human homolog, we named STRIP. We show that STRIP interacts with Connector of Kinase to AP-1 (CKA), a novel regulatory subunit for the PP2A phosphatase holoenzyme, both in insect S2 cells and in fly head extracts. Downregulation of both STRIP and/or CKA causes long-period behavioral phenotypes and high molecular weight forms of the CLK protein to accumulate in the morning. Perturbation of general PP2A activities also produces hyper-phosphorylated CLK in the morning indicating that, through CKA/STRIP, PP2A complexes controls CLK dephosphorylation at the end of the cycle. Hyper-phosphorylated CLK forms are transcriptionally inactive. Accordingly, transcription of the tim and vrille (vri) CLK targets is strongly reduced in Cka-RNAi fly head extracts. PP2A complexes containing the Widerborst (WDB) regulatory subunits were already shown to affect CLK stability in insect S2 cells (Kim and Edery, 2006). We show that WDB downregulation also affects the stability of CLK in fly head extracts, but has no apparent effects on CLK phosphorylation. Therefore, we could describe two different PP2A complexes acting on the CLK protein: PP2A/CKA/STRIP complex controls CLK dephosphorylation and reactivation, while PP2A/WDB affects CLK stability independently or after PP2A/CKA functions. Moreover, STRIP, but not CKA, downregulation affects the stability of PER, indicating that STRIP possesses some functions unrelated to CKA. In conclusion, this work has allowed the isolation of new components of the Drosophila molecular clock. In particular, we give evidence for a double role for the PP2A phosphatase in modulating the activity and stability of the CLK protein, the regulation of which is not well understood yet

Rest-activity circadian rhythm (RAR) analysis is a valuable tool to evaluate daily physical activity levels and sleep quality in breast cancer (BC) women, including BC survivors, a population less considered in the scientific literature. Indeed, the role of physical activity is recognised even in tertiary cancer prevention due to its action either on physical or psychological human spheres. In managing the quality of life in BC women, sleep assessment and its relationship with physical activity also raise attention. Several studies reported that an increase in physical activity practice might lead to better sleep quality. All these aspects have been less investigated in BRCA1/2 carrier women. BRCA1/2 are deleterious and high-invasive gene mutations, predisposing to a very aggressive breast and/or ovarian cancer also at a young age. The present PhD thesis evaluates RAR, sleep, and their relationship in two populations: a cohort of 5-year BC survivors and a sample of BRCA1/2 women. For the first study, 28 women (15 5-year BC survivors and 13 healthy controls) were 7-day long actigraph monitored and RAR analysis was performed with both parametric and non-parametric approaches. BC survivors showed a statistically lower MESOR (Midline Estimating Statistic of Rhythm), amplitude, L5 (nocturnal activity), and M10 (daily activity), while IV (Intradaily Variability) was higher than the control group. These results are the first experimental evidence that RAR alterations persist after 5 years since the primary diagnosis. Furthermore, BC survivors are less active than healthy controls and need practical intervention to increase their activity levels. For the second study, 27 women with BRCA1/2 mutations were 7-day long actigraph monitored, while 63 filled in the PSQI (Pittsburgh Sleep Quality Index) and the GSL-TPAQ (Godin Shepard Leisure-Time Physical Activity Questionnaire) questionnaires to assess sleep and physical activity, respectively. The 27 actigraph-monitored women were stratified, based on the development of cancer diagnosis, in affected and unaffected. RAR and actigraphic sleep analysis showed no statistically significant differences between the two groups, even though the affected women seemed to sleep worse than the unaffected. Based on the PSQI score, the women were stratified into good and bad sleepers: good sleepers were significantly more active than bad sleepers. Based on the GSL-TPAQ score, women were stratified into active and inactive: active women showed a better body composition and significantly lower insulin level and better sleep than inactive women. Finally, the regression analyses disclosed the positive effect of physical activity on sleep. More specifically, the prevalence ratio of being a good sleeper significantly increased with the increase in amount, intensity, and frequency of physical activity. This cross-sectional analysis of 63 women sheds light on a possible association between physical activity and sleep in BRCA1/2 mutation carriers. Considering the large attention that the BRCA1/2 carriers’ quality of life is receiving, a physical activity intervention could potentially improve the sleep quality in these women, also reflecting in an enhanced quality of life.

Background. Alterations in sleep and Rest-Activity circadian Rhythm (RAR) increase the risk of developing many pathological conditions, including Metabolic Syndrome (MS). Moreover, people with MS have been shown to sleep poorly and exhibit impaired RAR. Recently, metformin, an insulin sensitizer drug widely used in various cardiometabolic diseases, was introduced as adjuvant agent for the management of sleep disorders. It is shown to have an opposite effect to sleep disorders on the same parameters. The aim of my PhD project was to assess whether changes in daily habits are able to modify sleep, daily activity levels, sedentary habits and MS parameters in healthy people with MS, and also to investigate whether metformin treatment can modify sleep and MS parameters. Methods. 133 subjects with MS were enrolled in the study. At baseline and after one year of intervention, all participants underwent a medical examination to evaluate anthropometric and MS parameters. Also, they carried out a continuous 7-day actigraphic monitoring to investigate the RAR and sleep. Participants received double randomization, based on drug (metformin or placebo) and dietary approach (cooking courses or general awareness). Randomization based on drug treatment, adjusted for dietary approach, age, gender and baseline values, was considered for the data analysis. Results. At baseline, most subjects showed poor sleep quality and quantity. The comparison between the two sexes showed no differences in sleep parameters, and no difference was present between people with different severity of MS. Regarding RAR, influences related to sex have been found. Females showed higher daily movement and a less fragmented RAR compared to males. After one year of intervention, an improvement of MS in 45.7% of the participants was found. In 37.5% of them it was no longer possible to diagnose the MS. Metformin and placebo groups showed an improvement of their syndrome condition, with higher effects in metformin-treated subjects. A statistically significant increase in actual sleep time was found in metformin group at follow-up compared to baseline. Moreover, metformin-treated subjects showed an improvement of actual sleep time and sleep efficiency, while people treated with placebo displayed no change in actual sleep time, and a worsening in sleep efficiency. Although not significant, metformin group also showed a good trend of improvement in almost all other sleep parameters, while opposite trends were found in people treated with placebo. Regarding the RAR, the intervention showed no effects. This result was rather predictable, as a change in daily activity levels is required to modify the RAR, for example by encouraging strategies to increase daily activity and decrease sedentary behaviors. Conclusions. The results of this PhD research project support the hypothesis that metformin may be a new valid approach, together with a healthy eating style, for the secondary prevention not only of the metabolic syndrome condition but also of any related sleep disorders.

The thesis presents a series of papers exploring catatonic symptoms and circadian rest-activity levels in autistic spectrum disorders (ASD). The thesis is presented in paper-based format and encompasses a literature review, an empirical paper and a critical appraisal. Paper 1 is a systematic review of available treatments for autistic catatonia. Catatonic symptoms are thought to occur in around 8% of young people with ASD, and it has been suggested that biological timing abnormalities may play a key role in the development of these difficulties. Twenty two papers were included in the final review, detailing treatment of a total of 28 cases of autistic catatonia. Both adult and paediatric cases were included. The range of treatments described encompassed electroconvulsive therapy, various psychotropic medications, behavioural and sensory therapies. The review highlights limitations in the available literature and suggests avenues for future research. Paper 2 explores circadian patterns in activity using actigraphy. A case series of 8 young people with an ASD diagnosis were recruited from specialist schools and asked to wear an actigraph for one week. Parents completed questionnaire measures of ASD traits and symptoms of autistic catatonia. Findings indicated a high degree of variability in circadian rest-activity cycles, both between participants and across the week. The study findings have implications for future research into circadian rest-activity levels in this population, as well as possible therapeutic applications. The final paper in the thesis presents a critical appraisal of the research, including discussion of strengths and limitations of the work, theoretical and clinical implications and directions for future research. Some personal reflections on the process of conducting the research are also included.

La chronothérapie des cancers administre les médicaments anticancéreux à des moments précis de la journée afin d’en optimiser la tolérance et l’efficacité. Cependant le système circadien qui règle sur 24 h la prolifération et le métabolisme cellulaires peut être altéré par un décalage horaire chronique, la mutation d’un gène de l’horloge, ou un traitement, favorisant ainsi la survenue de pathologies métaboliques, comportementales ou malignes. La disparité des profils circadiens de température corporelle des patients cancéreux ainsi que leurs modifications sous chimiothérapie fournit les bases d’une personnalisation de la chronothérapeutique. La capacité d’un cycle thermique à entraîner sur 24 h l’horloge circadienne de cellules d’hépatocarcinome en culture indique que ce biomarqueur est aussi un effecteur de la synchronisation des cellules cancéreuses, et constitue un repère circadien pour la chronothérapeutique in vitro et in vivo<br>Chronotherapy delivers anticancer drugs at specific times of the day to optimize tolerability and efficacy. However, the circadian system that controls cell proliferation and metabolism over 24 h, can be altered by a chronic jet lag, a clock gene mutation, or a xeniobiotic treatment, thus favoring the occurrence of metabolic, behavioral or malignancies. The disparity of circadian body temperature patterns of cancer patients as well as its disruption during the treatment provides a clincher for chronotherapy personalization. The ability of a thermal cycle to drive the circadian clock in cultured hepatocarcinoma cells of 24 h indicates that this biomarker is also an effector of the synchronization of cancer cells, as well as a marker for the circadian in vitro and in vivo chronotherapeutic

Few biological systems are as ubiquitous as the circadian rhythm, a distributed yet inter-connected “system of systems” that coordinates the timing of physiological processes via a self-regulating, flexible network present at every level of biological organization, from cells to cities. Its functional role as the interface between time-dependent internal processes and external environmental cues exposes the circadian rhythm to disruption if these drift out of synchrony. This is especially common in industrialized human societies, where the abun-dance of resources – in combination with the fact that anthropogenic calendars have largely supplanted the sun as the primary determinant of our daily cycles of rest, activity, and sleep – disrupts the circadian rhythm’s ability to synchronize biological processes with each other and the geophysical solar day. Humans are now beholden to two increasingly disconnected clocks, and the ever-accelerating curve of human progress suggests our biological and so-cial times will only grow more disconnected. Longitudinal “out-of-clinic” monitoring is an ecologically valid alternative to well-controlled laboratory studies that can provide insight into how human circadian and behav-ioral rhythms exist in day-to-day life, and so has great potential to provide contextual data for translating chronobiological science into clinical intervention. However, methodological diversity, inconsistent terminology, insufficient reporting, and the sheer number of potential factors has slowed progress. Herein is presented scientific work focused on detecting and quantifying some of these factors, particularly “sociogenic” determinants such as the seven-day week. Through rhythmometric analysis of longitudinal in-home actigraphy, weekly be-havioral patterns were observed in both young adult males (n = 24, mean age = 23.46 years) and older adults with Parkinson’s disease (n = 13 [7 male], mean age = 60.62 years, mean Hoehn & Yahr Stage = 2.31) that evince a seven-day “circaseptan” rhythm of circadi-an and sleep disruption. This is hypothesized to be dependent upon the seven-day calendar week, particularly the regular and abrupt shifts in timing between work and rest days. These perturbations vary by chronotype in young adults, and by disease severity in Parkin-son’s disease. Collectively, these results contribute to the growing evidence that our daily rhythms are shaped by sociogenic factors in addition to well-documented environmental and biological mechanisms. Moreover, the study of these subtle infradian patterns presents serious – yet surmountable – methodological challenges that must be overcome in order to accurately monitor, quantify, analyze, report, and apply findings from observational studies of naturalistic human behavior to scientific and clinical problems.

Sleep medicine practice requires different objective procedures apart from nocturnal polysomnography (PSG) to quantify sleep patterns and daytime sleepiness. Two approaches are available to measure daytime sleep propensity and vigilance: the multiple sleep latency test (MSLT) and the maintenance of wakefulness test (MWT). Both tests require multiple nap opportunities under online dynamic PSG monitoring; however, in the MSLT, the subject is asked to try to fall asleep (and sleep 15 minutes to document sleep onset REM periods), but in the MWT to remain awake. The MSLT is the gold standard test for the differential diagnosis of central disorders of hypersomnolence after careful clinical assessment, while the MWT is useful to document vigilance levels for safety reasons. Rest–activity patterns can be documented for prolonged periods by actigraphy to measure circadian sleep distribution. Actigraphy is therefore a useful objective tool for insomnia, circadian rhythm, and sleepiness assessment and to track treatment response.

Almost all life shows a 24-hour pattern of activity and rest, as we live on a planet that revolves once every 24 hours, causing profound changes in light, temperature, and food availability. Species are adapted to a particular temporal niche just as they are to a physical niche. Activity at the wrong time often means death. We spend approximately 36 per cent of our lives asleep, which suggests this aspect of our 24-hour behaviour provides us with something of huge value. ‘Sleep: The most obvious 24-hour rhythm’ considers two questions: Why has almost all life evolved a 24-hour circadian pattern of activity and rest? And what are the important processes that occur in the body during sleep?

Most circadian clocks make use of a sun-based mechanism as the primary entraining signal to lock the internal day to the astronomical day. For nearly four billion years, dawn and dusk has been the main zeitgeber that allows entrainment. Circadian clocks are not exactly 24 hours. So to prevent daily patterns of activity and rest from freerunning over time, light can reset the clock. ‘Shedding light on the clock’ explains that the main circadian clock has been located in the suprachiasmatic nucleus in the hypothalamus. This also regulates the activity of the autonomic nervous system, but there are clocks in virtually every cell in the human body. Other zeitgebers include food, physical exercise, and temperature.

Circadian rhythms are endogenous 24-hour oscillations in physiology and behaviour that enable organisms to predict and adapt to the rhythmic changes of the day/night cycle. While the rhythm of activity and rest is perhaps the most familiar, changes in body temperature, heart rate, hormone production, and even cognitive function also occur. By contrast, the daily pattern of sleep and wake is not solely determined by the circadian system and is also regulated by a homeostatic process that increases with prolonged waking. Sleep and circadian rhythm disruption (SCRD) is commonly observed in psychiatric disorders, such as schizophrenia, although it is unclear as to the basis of this comorbidity. The chapter provides an overview of the links between SCRD and schizophrenia, highlighting the potential sources of this association. Moreover, the chapter describes how targeted treatment of the underlying sleep and circadian disruption in this patient group may provide a novel therapeutic avenue to ameliorate their primary symptoms.

New scientific evidence raises awareness concerning the human-specific interplay among primary environmental conditions, such as the light–dark cycle, activity–rest alternation, nutritional patterns, and their reflection on the physiological and pathological characteristics that are displayed uniquely by every individual. One of the critical aspects in the clinic is to understand the role of circadian rhythms as remarkable modulators of the biological effects of drugs and to aim for an optimal overlapping of the time of administration of medicines with the physiologic release of certain hormones, the time-dependent expression of genes, or the key-regulatory protein synthesis, which are all circadian-driven processes. The pharmacokinetics and pharmacodynamics profiles, as well as the possible drug interactions of neurotropic and cardiovascular agents, are intensely subjected to endogenous circadian rhythms, being essential to identify as much as possible the patients’ multiple risk factors, from age and gender to lifestyle elements imprinted by dietary features, sleep patterns, psychological stress, all the way to various other associated pathological conditions and their own genetic and epigenetic background. This review chapter will highlight the involvement of biological rhythms in physiologic processes and their impact on various pathological mechanisms, and will focus on the nutritional impact on the circadian homeostasis of the organism and neurologic and cardiovascular chronotherapy.

Actimetry has been shown to be useful for non-parametric analysis of biological activity/rest rhythms. We verified the pattern of activity and rest of 5 women from the city of Maringá/Pr during 30 days. We applied a sociocultural questionnaire (CONEP: 4,032,221). A (31), B (46), C (54), D (55), E (61) years. Total sleep time for A was between 6:00 am and 2:02 pm, with an average of 11 awakenings. For B, 5:10 am and 9:14 am, with an average of 21 awakenings. Participant C, 5:23 am and 10:16 am, with an average of 10 awakenings. For D, 6:02 am and 11:38 am, with an average of 16 awakenings. Participant E, 5:16 am and 8:14 am, with an average of 10 awakenings. All of them presented circadian rhythm and irregularities in sleeping and waking up during the week, with an increase in the number of hours slept on the weekends. They reported worsening sleep quality during the pandemic. When asked about the state of anxiety in relation to the moment, on a scale from zero to ten, participants A, B, C and D answered 9 and E answered 8. In relation to fear of possible health and financial risks, A, C and D scored 8, B and E scored 6 for health. A, B and C scored 9, E scored 6 and D scored 8 for the financier. We can infer that sleep suffers environmental/social influences. Actions that lead to selfknowledge can contribute to the recognition of sleep changes, allowing control and monitoring of real situations of external conflict.