Article

The Rhythms of Life - What your body clock means to you.

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Abstract

Until we turned our nights into days, and began to travel in aircraft across multiple time zones, we were largely unaware that we possess a 'day within' driven by an internal body clock. Yet the striking impairment of our abilities in the early hours of the morning soon reminds us that we are slaves to our biology. Our ability to perform mathematical calculations or other intellectual tasks between 04:00 - 06:00 in the morning is worse than if we had consumed several shots of whisky and would be classified as legally drunk. Biological clocks drive or alter our sleep patterns, alertness, mood, physical strength, blood pressure, and every other aspect of our physiology and behaviour. Our emerging understanding of how these 24 hour rhythms are generated and regulated is not only one of the great success stories of modern biology, but is also informing many areas of human health. Sleep and circadian rhythm disruption (SCRD) is a feature shared by some of the most challenging diseases of our time, including neuropsychiatric illness and serious disorders of the eye. SCRD is also commonly seen across many sectors of society, from teenagers to shift workers. We also now appreciate that SCRD is far more than feeling sleepy at an inappropriate time. It promotes multiple illnesses ranging across abnormal metabolism; heart disease; reduced immunity; increased stress; and abnormal cognition and mood states. This short review will consider how 24h rhythms are generated and regulated; the consequences of working against our body clock; and the emerging relationship between SCRD and mental illness.

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... These are synchronised by a sophisticated system of neuronal, hormonal and autonomous signalling [13]. Output signals from the clocks are subsequently generated, influencing physiological, psychological and behavioural processes [15]. The master and peripheral clocks of the circadian system synchronise through zeitgebers or time-givers [37]. ...
... Common time-givers are light, sleep-wake transition, physical activity, social cues and meals [38,39]. Light is arguably the most critical time-giver, as photic stimuli, via the retino-hypothalamic pathway, stimulates or inhibits the SCN [13,15,16,18]. The timing, intensity, duration and spectral composition of light appear to be the most critical factors in altering the timing of the circadian system [13,27] (Fig. 1). ...
... Melatonin is a hormone secreted by the pineal gland that aids in the process to consolidate sleep. The onset of secretion under dim light conditions, termed dim light melatonin onset (DLMO), occurs ~ 2 h before habitual bedtime and aligns with the start of the biological night [15][16][17][18]. The circadian rhythm of CBT oscillates ~ 0.8-1.0 ...
Article
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Athletes are increasingly required to travel domestically and internationally, often resulting in travel fatigue and jet lag. Despite considerable agreement that travel fatigue and jet lag can be a real and impactful issue for athletes regarding performance and risk of illness and injury, evidence on optimal assessment and management is lacking. Therefore 26 researchers and/or clinicians with knowledge in travel fatigue, jet lag and sleep in the sports setting, formed an expert panel to formalise a review and consensus document. This manuscript includes definitions of terminology commonly used in the field of circadian physiology, outlines basic information on the human circadian system and how it is affected by time-givers, discusses the causes and consequences of travel fatigue and jet lag, and provides consensus on recommendations for managing travel fatigue and jet lag in athletes. The lack of evidence restricts the strength of recommendations that are possible but the consensus group identified the fundamental principles and interventions to consider for both the assessment and management of travel fatigue and jet lag. These are summarised in travel toolboxes including strategies for pre-flight, during flight and post-flight. The consensus group also outlined specific steps to advance theory and practice in these areas.
... First, some jobs make it hard to follow a regular work-sleep schedule. When a person's work schedule and biological clock are out of sync, the schedule may force them to work while the body tells people to sleep, and vice versa [11]. For example, nurses and doctors often work during the night, and have to interrupt their sleep for patients and emergencies. ...
... For example, nurses and doctors often work during the night, and have to interrupt their sleep for patients and emergencies. This prevents them from forming a regular sleep-wake cycle [11]. Some shift workers "bank" their sleep to make up their sleep lost. ...
Conference Paper
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For many, healthy sleep is either not a priority or not a possibility, a deficit which has far-reaching consequences. We explore the potential for "sleepy games" as a genre of transformational games with embedded content, relevant in both the digital and physical design space. We present design challenges unique to sleepy games, synthesized through an iterative design process. Lights Out, one of nine sleepy games created, provides an example of our insights in context.
... Experimental evidence suggests that robustness and precision in daily timekeeping emerge in their collective behaviour mediated by intercellular communication of SCN networked cells [5,12]. Network desynchronization results in impaired circadian clock function, with implications in disorders such as sleep-wake problems, metabolic diseases and mental illness [13,14]. ...
... To resolve the apparent contradiction that GABA antagonists modestly enhance, and agonists dramatically enhance, synchrony among SCN cells [26,29,32,33,35,81], we considered the roles of GABA level and GABA A receptor density on simulated SCN neurons. We adjusted the GABA level sensed by each neuron by simultaneously adjusting all the scaling factors for both c iT and c iP (equations (7), (13) and (14) in the electronic supplementary material) for the SCN oscillators in our in silico model to simulate antagonist-induced blockade and agonist-induced stimulation of GABA signalling. As the GABA signalling level increased from 0% (full blockade) to royalsocietypublishing.org/journal/rsif J. R. Soc. ...
Article
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In the suprachiasmatic nucleus (SCN), γ-aminobutyric acid (GABA) is a primary neurotransmitter. GABA can signal through two types of GABA A receptor subunits, often referred to as synaptic GABA A (gamma subunit) and extra-synaptic GABA A (delta subunit). To test the functional roles of these distinct GABA A in regulating circadian rhythms, we developed a multicellular SCN model where we could separately compare the effects of manipulating GABA neurotransmitter or receptor dynamics. Our model predicted that blocking GABA signalling modestly increased synchrony among circadian cells, consistent with published SCN pharmacology. Conversely, the model predicted that lowering GABA A receptor density reduced firing rate, circadian cell fraction, amplitude and synchrony among individual neurons. When we tested these predictions, we found that the knockdown of delta GABA A reduced the amplitude and synchrony of clock gene expression among cells in SCN explants. The model further predicted that increasing gamma GABA A densities could enhance synchrony, as opposed to increasing delta GABA A densities. Overall, our model reveals how blocking GABA A receptors can modestly increase synchrony, while increasing the relative density of gamma over delta subunits can dramatically increase synchrony. We hypothesize that increased gamma GABA A density in the winter could underlie the tighter phase relationships among SCN cells.
... The daily organization of the rest-activity cycle can be more fragmented in this group, especially among the obese and with lower cardiorespiratory function, and is correlated with greater metabolic risk. 6 Still, disturbances of sleep and circadian rhythm are also commonly seen since adolescents to shift workers and can promote numerous diseases ranging from abnormal metabolism, heart disease, reduced immunity, increased stress, abnormal cognition and mood states. 6 A recent study that analyzed the adoption of healthy lifestyles among teenage students in Brazil from 2009 to 2015 found a decrease in the proportion of those physically active in all socioeconomic strata; this raised concerns about the extensive loss of health benefits from regular exercise among these groups. ...
... 6 Still, disturbances of sleep and circadian rhythm are also commonly seen since adolescents to shift workers and can promote numerous diseases ranging from abnormal metabolism, heart disease, reduced immunity, increased stress, abnormal cognition and mood states. 6 A recent study that analyzed the adoption of healthy lifestyles among teenage students in Brazil from 2009 to 2015 found a decrease in the proportion of those physically active in all socioeconomic strata; this raised concerns about the extensive loss of health benefits from regular exercise among these groups. 7 In addition, sedentary behavior regarding recreational screen time (for example, electronic media such as TV, smartphones, computers, video games, etc.) has been associated with a variety of damage to the health of children and adolescents. ...
Article
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Este estudo teve como objetivo comparar os níveis de atividade física (NAF), duração de sono e tempo de tela conforme fatores sociodemográficos de 95 adolescentes da faixa etária entre 14 e 18 anos. Os adolescentes responderam questionário sociodemográfico, Physical Activity Questionnaire for Adolescents e questões de autorrelato sobre o tempo de tela e duração do sono. Foi aplicado o Teste U de Mann-Whitney. Observou-se que 80% dos escolares não atendem às recomendações de atividade física, 54,7%, de horas de sono, e 77,9%, de tempo de tela. O sexo masculino apresentou maior NAF, escolares do turno vespertino tiveram mais horas de sono nos dias úteis e entre participantes com maior renda houve maior tempo de tela e menos horas de sono nos dias úteis. Concluiu-se que os fatores sociodemográficos como sexo, turno de estudo e renda mensal influenciam o NAF, a duração do sono e o tempo de tela de escolares.
... For example, they may have to sleep in a place that is noisy or brightly lit [28] [45] [53]. Their sleep environment may include regular interruptions, such as nurses or doctors who are on-call during the night [21]. Sleepers also may not have access to the resources that would allow them to sleep well, such as going to bed hungry because no food is available. ...
... For example, shift workers can have difficulty following a regular work-sleep schedule if working nighttime hours. If a shift worker's schedule is out of sync with their biological clock, they may be required to work while their body is telling them to sleep, and vice versa [21]. In an attempt to make up for missing sleep, some shift workers try to "bank" their sleep; however, even a single night of sleep deprivation can affect memory and cognition [27]. ...
... Many vertebrates use light-sensing proteins, called opsins, in order to seize and translate light information from their surroundings. Not only for vision but also non-visual purposes, such as the entrainment of internal circadian rhythms in mammals (e.g., reviewed in Foster and Kreitzman, 2014;Hang et al., 2016;Leung and Montell, 2017). Non-visual photoreception was already noted more than 100 years ago in experiments on blinded and pinealectomized minnows (von Frisch, 1911). ...
... Non-visual photoreception was already noted more than 100 years ago in experiments on blinded and pinealectomized minnows (von Frisch, 1911). A puzzling variety of opsins has been described, grouped according to their structural, functional, and temporal properties, and linked to non-visual/extraretinal photoreception in various vertebrate tissues, including the brain (Soni and Foster, 1997;Kojima and Fukada, 1999;Moutsaki et al., 2000;Philp et al., 2000a,b;Ekström and Meissl, 2003;Peirson et al., 2009;Porter et al., 2012;Foster and Kreitzman, 2014;Hunt et al., 2014;Davies et al., 2015). Pelagic fish, in particular, possess a whole array of non-visual opsins, e.g., ∼25 opsin genes in Neoteleosts, to which the clade medaka fish belong, and even 42 opsin genes in Zebrafish, making them "swimming photoreceptors" (Davies et al., 2015;Beaudry et al., 2017). ...
Article
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One of the big challenges in the study of animal behavior is to combine molecular-level questions of functional genetics with meaningful combinations of environmental stimuli. Light and temperature are important external cues, influencing the behaviors of organisms. Thus, understanding the combined effect of light and temperature changes on wild-type vs. genetically modified animals is a first step to understand the role of individual genes in the ability of animals to cope with changing environments. Many behavioral traits can be extrapolated from behavioral tests performed from automated motion tracking combined with machine learning. Acquired datasets, typically complex and large, can be challenging for subsequent quantitative analyses. In this study, we investigate medaka behavior of tmt-opsin2 mutants vs. corresponding wild-types under different light and temperature conditions using automated tracking combined with a convolutional neuronal network and a Hidden Markov model-based approach. The temperatures in this study can occur in summer vs. late spring/early autumn in the natural habitat of medaka fish. Under summer-like temperature, tmt-opsin2 mutants did not exhibit changes in overall locomotion, consistent with previous observations. However, detailed analyses of fish position revealed that the tmt-opsin2 mutants spent more time in central locations of the dish, possibly because of decreased anxiety. Furthermore, a clear difference in location and overall movement was obvious between the mutant and wild-types under colder conditions. These data indicate a role of tmt-opsin2 in behavioral adjustment, at least in part possibly depending on the season.
... Repeated long-haul flights also increase the risk of potential cognitive deficits or psychotic and major affective disorders [7]. In the long run, sleep and circadian rhythm disruption are reported to be associated with a broad range of interconnected pathologies, such as reduced motivation, depression, metabolic abnormalities, obesity, immune impairment, and even a greater risk of cancer [8,9]. ...
Article
We intend to examine whether behavioral and mental health-related determinants including stress level, daytime sleepiness, sleep disorders, smoking, drinking, physical activity, and vegetable intake were associated with severity of jet lag and symptoms of jet lag. We delivered a survey to All Nippon Airways HOLDINGS (ANA) customers in Japan and U.S. asking for their lifestyle information, subjective jet lag perceptions, and symptoms of jet lag, and obtained a sample of 1759 Japanese and 483 U.S. participants. Multivariate linear regression analysis showed a positive association between severity of jet lag perception and sleep disorders (Model 2: [b = 0.43, 95% CI 0.25; 0.61]), but a negative association between severe jet lag perception and both smoking (Model 2: [b = − 0.15, 95% CI − 0.30; − 0.00]) and physical activity (Model 2: [b = − 0.15, 95% CI − 0.28; − 0.02]). Regarding jet lag symptoms, it revealed a positive association between higher jet lag symptoms and perceived stress (Model 2: [b = 0.32, 95% CI 0.16; 0.47]), sleep disorder (Model 2: [b = 0.32, 95% CI 0.19; 0.44]), and vegetable consumption (Model 2: [b = 0.09, 95% CI 0.00; 0.17]). The results varied for other lifestyle factors, including smoking, physical activity, vegetable intake, and alcohol consumption. Given the health risks among business travelers, this preliminary analysis showed the possible importance of developing evidence-based jet lag prevention strategies.
... Animal studies [14,15] have shown that food intake can serve as a major time cue for peripheral tissue clocks, such as the liver, but not for the SCN. Conflicting zeitgeber timings can lead to internal desynchrony, a state in which different clocks throughout the body are out of sync [16]. In this experiment, we quantitated several parameters that characterize daily rhythm: the acrophase, amplitude, and MESOR, along with diurnality score. ...
Article
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Food consumption during the rest phase promotes circadian desynchrony, which is corrected with harmful physiological and mental disorders. Previously, we found that circadian desynchrony was involved in isoflurane-induced cognitive impairment. Here, we scheduled food access to modulate daily rhythm to examine its impact on isoflurane-induced cognitive impairments. Mice were randomly transferred to restricted feeding (RF) time groups: Control group (Zeitgeber time (ZT) 0–ZT24, ad libitum feeding), Day-Feeding group (ZT0–ZT12, misaligned feeding), and Night-Feeding group (ZT12–ZT24, aligned feeding). Then, some of them were subjected to 5 h of 1.3% isoflurane anaesthesia from ZT14 to ZT19 and were divided into the Control + Anes group, the Day-Feeding + Anes group, and the Night-Feeding + Anes group. Mini-Mitter was used to monitor the daily rhythm. Fear conditioning system was conducted to assess cognition of mice. We observed that the Night-Feeding group adapted to RF gradually, whereas the Day-Feeding group exhibited a disturbed daily rhythm. The Night-Feeding + Anes group exhibited a partially enhanced daily rhythm, whereas the Day-Feeding + Anes group exhibited sustained phase advances and diurnality score increase 7 days after isoflurane anaesthesia. Notably, in tests of hippocampus-dependent contextual memory, the Night-Feeding + Anes group demonstrated decreased deficits; the Day-Feeding + Anes group showed prolonged post-anaesthetic deficits 14 days after isoflurane anaesthesia. However, amygdala-dependent cued-fear conditioning post-anaesthesia was not altered by the RF schedule. In conclusion, we demonstrated that misaligned feeding disturbed the daily rhythm and led to persistent post-anaesthetic cognitive dysfunction. Aligned feeding enhanced the daily rhythm partially and improved post-anaesthetic cognitive dysfunction.
... Zeitgebers include environmental time cues such as light, food, noise, or social interaction, which help to reset the biological clock to a 24-hour day [11,14] . The clock translates environmental information on day length, social contact, and seasonal changes into hormonal messages that are sent throughout the body to set the clock of other organs [11,17] . Secretion of melatonin (a hormone that induces sleep) is highest at night and falls during the day [5,25] . ...
Article
Biobehavioral rhythms are associated with numerous health and life outcomes. We study the feasibility of detecting rhythms in data that is passively collected from Fitbit devices and using the obtained model parameters to predict readmission risk after pancreatic surgery. We analyze data from 49 patients who were tracked before surgery, in hospital, and after discharge. Our analysis produces a model of individual patients' rhythms for each stage of treatment that is predictive of readmission. All of the rhythm-based models outperform the traditional approaches to readmission risk stratification that uses administrative data.
... 10 These nuclei generate the endogenous circadian rhythms in rest-activity and body temperature, which have been proposed as CTS biomarkers 10 and are used here for such purpose. Our current understanding of circadian rhythms as a network of molecular clocks and their relevance for human health has quickly progressed 11,12 and it is now imminent that they become integrated into medical decision processes. 13À15 Shiftwork-induced CTS disruption is experimentally-modelled with chronic jet lag exposure. ...
Article
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Background: Telemonitoring of circadian and sleep cycles could identify shift workers at increased risk of poor health, including cancer and cardiovascular diseases, thus supporting personalized prevention. Methods: The Circadiem cross-sectional study aimed at determining early warning signals of risk of health alteration in hospital nightshifters (NS) versus dayshifters (DS, alternating morning and afternoon shifts). Circadian rhythmicity in activity, sleep, and temperature was telemonitored on work and free days for one week. Participants wore a bluetooth low energy thoracic accelerometry and temperature sensor that was wirelessly connected to a GPRS gateway and a health data hub server. Hidden Markov modelling of activity quantified Rhythm Index, rest quality (probability, p1-1, of remaining at rest), and rest duration. Spectral analyses determined periods in body surface temperature and accelerometry. Parameters were compared and predictors of circadian and sleep disruption were identified by multivariate analyses using information criteria-based model selection. Clusters of individual shift work response profiles were recognized. Findings: Of 140 per-protocol participants (133 females), there were 63 NS and 77 DS. Both groups had similar median rest amount, yet NS had significantly worse median rest-activity Rhythm Index (0·38 [IQR, 0·29-0·47] vs. 0·69 [0·60-0·77], p<0·0001) and rest quality p1-1 (0·94 [0·94-0·95] vs 0·96 [0·94-0·97], p<0·0001) over the whole study week. Only 48% of the NS displayed a circadian period in temperature, as compared to 70% of the DS (p=0·026). Poor p1-1 was associated with nightshift work on both work (p<0·0001) and free days (p=0·0098). The number of years of past night work exposure predicted poor rest-activity Rhythm Index jointly with shift type, age and chronotype on workdays (p= 0·0074), and singly on free days (p=0·0005). Interpretation: A dedicated analysis toolbox of streamed data from a wearable device identified circadian and sleep rhythm markers, that constitute surrogate candidate endpoints of poor health risk in shift-workers. Funding: French Agency for Food, Environmental and Occupational Health & Safety (EST-2014/1/064), University of Warwick, Medical Research Council (United Kingdom, MR/M013170), Cancer Research UK(C53561/A19933).
... It would also be important as the commercial spaceflight field expands for passengers and pilots who regularly fly orbital or suborbital flights between, say, New York City and Tokyo. This is because the circadian rhythms of the cells in most peripheral tissues are uncoupled into their own circadian rhythms by crossing time zones in a jet plane or spaceflight [32]. Moreover, enrichment analysis in the tissue-wide analysis enriched herpes simplex infection and endocrine system development as prevalent molecular mechanisms across tissues ( Figure 1C). ...
Article
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Rodent models have been widely used as analogs for estimating spaceflight-relevant molecular mechanisms in human tissues. NASA GeneLab provides access to numerous spaceflight omics datasets that can potentially generate novel insights and hypotheses about fundamental space biology when analyzed in new and integrated fashions. Here, we performed a pilot study to elucidate space biological mechanisms across tissues by reanalyzing mouse RNA-sequencing spaceflight data archived on NASA GeneLab. Our results showed that clock gene expressions in spaceflight mice were altered compared with those in ground control mice. Furthermore, the results suggested that spaceflight promotes asynchrony of clock gene expressions between peripheral tissues. Abnormal circadian rhythms are associated not only with jet lag and sleep disorders but also with cancer, lifestyle-related diseases, and mental disorders. Overall, our findings highlight the importance of elucidating the causes of circadian rhythm disruptions using the unique approach of space biology research to one day potentially develop countermeasures that benefit humans on Earth and in space.
... Human lives are defined by rhythms of different frequency: daily, weekly, seasonal, and annual, among others. The most prominent rhythms in our lives are rooted in the day-night cycle 1 . From body cell functions to social activities and interactions, many aspects of human lives follow diurnal rhythms 2 . ...
Preprint
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Human activities follow daily, weekly, and seasonal rhythms. The emergence of these rhythms is related to physiology and natural cycles as well as social constructs. The human body and biological functions undergo near 24-hour rhythms (circadian rhythms). The frequency of these rhythms is more or less similar across people, but its phase is different. In the chronobiology literature, based on the propensity to sleep at different hours of the day, people are categorized into morning-type, evening-type, and intermediate-type groups called \textit{chronotypes}. This typology is typically based on carefully designed questionnaires or manually crafted features drawing on data on timings of people's activity. Here we develop a fully data-driven (unsupervised) method to decompose individual temporal activity patterns into components. This has the advantage of not including any predetermined assumptions about sleep and activity hours, but the results are fully context-dependent and determined by the most prominent features of the activity data. Using a year-long dataset from mobile phone screen usage logs of 400 people, we find four emergent temporal components: morning activity, night activity, evening activity and activity at noon. Individual behavior can be reduced to weights on these four components. We do not observe any clear emergent categories of people based on the weights, but individuals are rather placed on a continuous spectrum according to the timings of their activities. High loads on morning and night components highly correlate with going to bed and waking up times. Our work points towards a data-driven way of categorizing people based on their full daily and weekly rhythms of activity and behavior, rather than focusing mainly on the timing of their sleeping periods.
... Other stimuli that are relevant for survival, such as food availability, feeding routine, social interaction and the sleepwake cycle, also provide inputs to the circadian system (Refinetti, 2012). Predictable daily environmental cycles allow the organism to adapt to and anticipate these external cyclical changes, which have been shown to be relevant for health and wellness (Foster and Kreitzman, 2014;Hastings et al., 2003;Kim and Duffy, 2018;Reinberg et al., 2015). ...
Article
The circadian system organizes circadian rhythms (biological cycles that occur around 24 h) that couple environmental cues (zeitgebers) with internal functions of the organism. The misalignment between circadian rhythms and external cues is known as chronodisruption and contributes to the development of mental, metabolic and other disorders, including cancer, cardiovascular diseases and addictive disorders. Drug addiction represents a global public health concern and affects the health and well-being of individuals, families and communities. In this manuscript, we reviewed evidence indicating a bidirectional relationship between the circadian system and the development of addictive disorders. We provide information on the interaction between the circadian system and drug addiction for each drug or drug class (alcohol, cannabis, hallucinogens, psychostimulants and opioids). We also describe evidence showing that drug use follows a circadian pattern, which changes with the progression of addiction. Furthermore, clock gene expression is also altered during the development of drug addiction in many brain areas related to drug reward, drug seeking and relapse. The regulation of the glutamatergic and dopaminergic neurocircuitry by clock genes is postulated to be the main circadian mechanism underlying the escalation of drug addiction. The bidirectional interaction between the circadian system and drug addiction seems to be mediated by the effects caused by each drug or class of drugs of abuse. These studies provide new insights on the development of successful strategies aimed at restoring/stabilizing circadian rhythms to reduce the risk for addiction development and relapse.
... The normal 24-hour rhythms of sleep and wakefulness are maintained by a body clock mechanism, which utilises information about the external world from photoreceptors within the eyes as well as internal information about sleep pressure which builds up during wakefulness, to regulate sleep (Foster & Kreitzman, 2014). Daily routines such as mealtimes and regular activities like getting dressed and being engaged in activity during the day also contribute to the rhythm (Yoshizaki et al., 2013). ...
Article
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Sleep problems have a negative impact on a range of outcomes and are very common in adolescents with chronic fatigue syndrome (CFS). We aimed to (a) establish whether adolescents with CFS have more self-reported sleep problems than illness controls as well as healthy controls, (b) investigate changes in sleep problems and (c) explore the extent to which sleep problems at baseline predict fatigue and functioning at follow-up in adolescents with CFS. The Insomnia Scale was completed by 121 adolescents with CFS, 78 healthy adolescents and 27 adolescents with asthma. Eighty (66%) treatment-naïve adolescents with CFS completed questionnaires approximately 3 months later. Adolescents with CFS reported increased sleep problems compared to healthy controls and adolescents with asthma. In CFS, there was no significant change in sleep problems without treatment over a 3-month follow-up. Sleep problems at baseline predicted a significant proportion of the variance in sleep problems at follow-up. Sleep problems should be targeted in treatment. Regulating the ‘body clock’ via the regulation of sleep could influence outcomes not assessed in this study such as school attainment.
... Neurons generating rhythms in gene expression and firing frequency are coupled together for robustness and synchronized to establish 24-hour circadian rhythms for regulating various physiological and behavioral processes (Belle and Diekman, 2018;Hastings et al., 2014;Welsh et al., 2010). Impairment of the circadian clock has been implicated in numerous disorders including sleep problems, mental illness, and metabolic diseases (Foster and Kreitzman, 2014;Liu et al., 2007). Neuronal coupling is mediated by neurotransmitters triggered by action potentials and released from presynaptic neurons Colwell, 2011;Herzog et al., 2017). ...
Article
The suprachiasmatic nucleus (SCN) of the hypothalamus consists of a highly heterogeneous neuronal population networked together to allow precise and robust circadian timekeeping in mammals. While the critical importance of SCN neurons in regulating circadian rhythms has been extensively studied, the roles of SCN astrocytes in circadian system function are not well understood. Recent experiments have demonstrated that SCN astrocytes are circadian oscillators with the same functional clock genes as SCN neurons. Astrocytes generate rhythmic outputs that are thought to modulate neuronal activity through pre- and postsynaptic interactions. In this study, we developed an in silico multicellular model of the SCN clock to investigate the impact of astrocytes in modulating neuronal activity and affecting key clock properties such as circadian rhythmicity, period, and synchronization. The model predicted that astrocytes could alter the rhythmic activity of neurons via bidirectional interactions at tripartite synapses. Specifically, astrocyte-regulated extracellular glutamate was predicted to increase neuropeptide signaling from neurons. Consistent with experimental results, we found that astrocytes could increase the circadian period and enhance neural synchronization according to their endogenous circadian period. The impact of astrocytic modulation of circadian rhythm amplitude, period, and synchronization was predicted to be strongest when astrocytes had periods between 0 and 2 h longer than neurons. Increasing the number of neurons coupled to the astrocyte also increased its impact on period modulation and synchrony. These computational results suggest that signals that modulate astrocytic rhythms or signaling (e.g., as a function of season, age, or treatment) could cause disruptions in circadian rhythm or serve as putative therapeutic targets.
... The expression of many genes changes rhythmically over 24 h and the specific circadian genes are responsible for the main SCN clock-working machinery as well as that of subsidiary clocks at the peripheral level [among them: circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like protein 1 (BMAL1), cryptochromes CRY1-2, and band period homolog (PER)] [ (15,16); for an overview see Ref. (17)]. The suprachiasmatic nuclei is daily synchronized by environmental signals such as light, food intake, activities, or social cues and exposure to stress/trauma (18)(19)(20), and while driving, secretion of the melatonin hormone regulates peripheral clock within feed-forward mechanism. Rhythmic clock gene expression regulates multiple monoaminergic brain regions that control mood and motivational behaviors, stress and inflammatory systems, reward circuits, arousal, and sleep by interacting with the homeostatic regulation of sleep and wake [for an overview, see Refs. ...
Article
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Background: A compelling number of studies, conducted in both children and adults, have reported an association between sleep disturbances/circadian sleep alterations and autism spectrum disorder (ASD); however, the data are sparse and the nature of this link is still unclear. The present review aimed to systematically collect the literature data relevant on sleep disturbances and circadian sleep dysrhythmicity related to ASD across all ages and to provide an integrative theoretical framework of their association. Methods: A systematic review of the MEDLINE, PubMed, and Cochrane databases was conducted from November 2018 to February 2019. The search strategies used were MeSH headings and keywords for "sleep-wake circadian rhythms" OR "circadian sleep disorders" OR "sleep-wake pattern" OR "sleep disorders" OR "melatonin" AND "autism spectrum disorder" OR "autism". Results: One hundred and three studies were identified, 15 regarded circadian sleep dysrhythmicity, 74 regarded sleep disturbances, and 17 regarded melatonin alterations in children and adults with ASD. Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration, low sleep quality/efficiency, and circadian sleep desynchronization such as delayed phases and/or eveningness. Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms. Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD. Conclusions: Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms. These subjects have shown polymorphisms in clock genes expression and in genes involved in melatonin production. The impairment of circadian sleep regulation may increase the individual's vulnerability to develop symptoms of ASD by altering the sleep regulation in toto, which plays a key role in normal brain development. Even though controversies and "research gaps" are present in literature at this point, we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD. In particular, circadian sleep dysrhythmicity may predispose to develop ASD symptoms and vice versa within a self-reinforcing feedback loop. By targeting sleep disturbances and circadian sleep dysrhythmicity, we may improve treatment strategies for both children and adults with ASD.
... Many biobehavioral processes in humans, including sleep-wake behavior, follow a diurnal pattern, often called a circadian rhythm. Circadian rhythms are endogenous rhythmic patterns in multiple physiological and behavioral processes such as sleepwake patterns, rest-activity patterns, mood, cognitive function, body temperature, heart rate, and hormone secretions that are entrained to a 24-h day to enable individuals to anticipate and adapt to periodic environmental changes (8)(9)(10). Optimal circadian entrainment, exhibiting a 24-h period with an appropriate amplitude (strength) and phase (timing), is essential for the optimization of physical, psychological, and behavioral functions and overall human health (9,10). ...
Article
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Background: Little is known about sleep and circadian rhythms in survivors of acute respiratory failure (ARF) after hospital discharge. Objectives: 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. Methods: 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. Results: 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 (p < 0.001), and weaker circadian strength (p < 0.001). Conclusion: 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.
... Hence, the organism experiences light exposure during the subjective night and darkness during the subjective day. As a consequence, symptoms of irritability, malaise, diarrhea, and cognitive impairment are experienced [2]. Eventually, the organism's clock resynchronizes to the new environment due to the regular new light stimulus, glucocorticoid signaling, and other signals, such as melatonin and metabolic signals [3,4]. ...
Article
The circadian system consists of individual cellular clocks. It organizes and synchronizes biochemical and physiological processes in order to optimally adapt an organism to its environment. This requires that the circadian system is responsive to environmental cues, which contain information about geophysical time (e.g., light), and allows an organism to predict daily recurring events. However, the system needs to be responsive to unpredictable cues (e.g., predators, stress) as well, which makes it vulnerable in its task to synchronize body functions on a 24-h time scale. If unpredictable signals occur only occasionally, this will have a minor effect on the clock system. Conversely, stress signals that occur more frequently will desynchronize the various cellular and tissue clocks in the body. This will result in biochemical and physiological disorder and as a consequence will lead to various diseases including neurological and mood disorders. In this review, I will describe molecular mechanisms that have been associated with the circadian clock and mood-related behaviors.
... Sleep is indispensable for the homeostasis of organisms, and is closely associated with circadian rhythms (Goel et al., 2013) and hormone levels (Mônico-Neto et al., 2015). The number of people suffering from sleep disorders is increasing, particularly those who only sleep for a few hours each night (Foster and Kreitzman, 2014). This represents a major issue because sleep disorders are known to increase the risk of some diseases, including obesity (Van Cauter et al., 2008), diabetes (Chao et al., 2011), cancer (Haus and Smolensky, 2013), cardiovascular diseases (Chaput et al., 2013;McAlpine et al., 2019), Alzheimer Disease, and dementia (Pistollato et al., 2016). ...
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A lack of sleep is linked with a range of inner ear diseases, including hearing loss and tinnitus. Here, we used a mouse model to investigate the effects of sleep deprivation (SD) on noise vulnerability, and explored the mechanisms that might be involved in vitro, focusing particularly corticosterone levels and autophagic flux in cells. Female BALB/c mice were divided into six groups [control, acoustic trauma (AT)-alone, 1 day (d) SD-alone, 1d SD pre-AT, 5d SD-alone, and 5d SD pre-AT]. Cochlear damage was then assessed by analyzing auditory brainstem response (ABR), and by counting outer hair cells (OHCs) and the synaptic ribbons of inner hair cells (IHCs). In addition, we measured levels of serum corticosterone and autophagy protein expression in the basilar membranes by ELISA kits, and western blotting, respectively. We found that SD-alone temporarily elevated ABR wave I amplitude, but had no permanent effect on hearing level or IHC ribbon numbers. Combined with AT, the number of synaptic ribbons in the 1d SD pre-AT group was significantly higher than that in the AT-alone group, whereas the 5d SD pre-AT group showed more severe synaptopathy, and a greater loss of OHCs after 2 weeks than the other experimental groups exposed to noise. Correspondingly, the levels of corticosterone in the AT-alone group were higher than those of the 1d SD pre-AT group, but lower than those of the 5d SD pre-AT group. The 1d SD pre-AT group showed a marked elevation in the expression of microtubule-associated protein 1 light chain 3B (LC3B), whereas the AT-alone group exhibited only a mild increase. In contrast, the levels of LC3B did not change in the 5d SD pre-AT group. Experiments with HEI-OC-1 cells and cochlear basilar membrane cultures showed that high-concentrations of dexamethasone, and the inhibition of autophagy, aggravated cellular apoptosis induced by oxidative stress. In conclusion, noise-induced synaptopathy and hair cell loss can be mitigated by preceding 1d SD, but will be aggravated by preceding 5d SD. These findings may be attributable to corticosterone levels and the extent of autophagy.
... Compared to evening-types, morning-types prefer earlier sleep schedules and exhibit an acrophase advance regarding physiological circadian markers, such as endogenous core body temperature and melatonin secretion, meaning these phenomena reach their zenith (i.e., peak) earlier in relation to the external clock time (Mongrain et al. 2004;Schmidt et al. 2007;Cuesta et al. 2017). In fact, most biological phenomena manifest circadian oscillations along the 24-h cycle (Foster and Kreitzman 2014;Ospri et al. 2017), including psychological variables such as subjective well-being (Birchler-Pedross et al. 2009), alertness (Vollmer et al. 2013), attention , mood (Díaz-Morales et al. 2015), and positive affect (Murray et al. 2002). Chronotype can be determined through actigraphy or biomarkers, such as cortisol and melatonin secretion levels (Adan et al. 2012;Randler and Engelke 2019). ...
Article
The present study primarily aimed to investigate the interactive effect of chronotype and time of day on adolescent’s emotional states. Chronotype influences behaviour throughout the day, with variables such as mood exhibiting circadian rhythmicity. We also considered the influence of potential covariates, such as sleep variables and psychopathological symptoms. A total of 190 8th-grade students (53.7% males; mean age 13.47 ±.70) completed a two-part protocol: part one probing sleep (BaSIQS), chronotype (CSM), and psychopathological symptoms (SDQ); part two targeting emotional states (FS; STAIC-S; EAPNC), while manipulating the time of day (first and last hours of the school day). The hypothesized interaction failed to reach significance, despite correlational analyses and visual inspection of mean values suggesting some interactive effects. Time of day independently impacted positive emotional states, rising from morning to afternoon, and anxiety-state, which dropped. Chronotype independently influenced momentary mood (non-significant when sleep and psychopathological symptoms were controlled for), positive affect (non-significant when controlling for psychopathological symptoms), and anxiety (non-significant when sleep quality and psychopathological symptoms were controlled for). There were consistent effects of time of day, but its interaction with chronotype did not reach significance. Some associations between chronotype and emotional states seemed to be influenced by sleep and/or psychopathological symptoms.
... Biological rhythms as the third analytics component considers the human's circadian rhythms that drive the patterns of cognitive, behavioural, and physiological processes. As the biological clocks influence, among others, activity, sleep, and mood, rhythm disruption can lead to consequences like reduced motivation, performance, and health [9]. In order to determine biological rhythms or their disruption, especially body sensor information like sleep and activity timings and also heart rate variability may be relevant. ...
Conference Paper
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The development of the knowledge-based society and ubiquitous information technology offer individuals a variety of personal and professional possibilities. At the same time, increasing flexibility in modern everyday life can lead to high working pressure and blurring boundaries between life domains. Thus, self-management skills steadily grow in importance. These skills are not only important for productivity, but also for health and wellbeing. The availability of various small sensors and their easy integration into everyday life enables new kinds of data collection. Data ranging from heart rate to location can be analysed and combined with data about tasks and time schedule to provide guidance in self-management. However, up to now it is unclear how such a guidance based on sensor information could be designed and how it can positively contribute to self-management. In our research, we hence provide a first contribution towards context-aware assistance for self-management of knowledge workers. To do so, we first devise a scenario to show how such a system could positively contribute to self-management via a set of interventions based on sensor data. We then present an architecture that conceptualises a context aware system integrating several data sources along with descriptions of implementation options of such a system. With this, we intend to provide an overview on the design space relevant for the construction of such systems. This overview is meant to inform and inspire the future design of concrete systems that assist knowledge workers in the enhancement of their self-management skills. Source: http://ceur-ws.org/Vol-2218/paper1.pdf
... Circadian rhythms determine rhythmic changes in physiological and behavioral aspects, such as body temperature, cortisol levels, melatonin and growth hormone, mood, cognitive ability, and especially the sleep and wake cycle. Indeed, being awake or sleeping at different times of the day and night is not only due to a situation of fatigue or exhaustion, but rather due to the innate rhythms that determine the pattern of days and nights (1) .In general, the regulation and control of the sleep and wake cycle are attributed to the hypothalamic systems and their respective functional interactions with other structures of the central nervous system, in particular, the cerebral cortex (2,3) . In this sense, sleep is a fundamental and cyclical process of the organism, which exerts several biological and psychological functions, for example, the energy metabolism restoration and the memory consolidation; which can be conceptualized as a reversible behavioral state, in which characteristic features such as relaxed posture, minimal movements, perceptive disengagement and increased threshold of responses to external stimuli can be observed (4)(5)(6)(7) . ...
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Purpose: The present study aimed evaluated the influence of exercise program on sleep quality of sedentary individuals. Methods: The study evaluated 30 subjects after resistance training session constituted by six multi-joints exercises (leg press, chest press, machine let pull down, seated machine shoulder press, crunches and machine trunk extension) three times a week for 40 days. The intensity of the effort was controlled using the follow criteria: the ideal repetitions for each set was between eight and fifteen. The Pittsburgh Sleep Quality Questionnaire (PSQI) was applied before and after training period. Results: There was a significant effect of short-term resistance training on all sub-scores of PSQI (p<0.05), except for sleep duration (p>0.05). Conclusion: The resistance training program was able to improve the sleep quality in healthy subjects. In addition, the applicability of low-cost instruments (psychometric instruments like PSQI) to evaluate health parameters, which could be strengthened by other studies.
... The normal circadian network is disturbed and leads to systemic adaptations that entrain the cardiovascular system to operate at a raised blood pressure modifying the equilibrium and increases the probability of hypertension. [27,28] ...
... Rhythms are common across biological systems, from circadian cycles (Foster & Kreitzman, 2014), to locomotion (Lacquaniti et al., 2012), to the auditory communication Abbreviations: ANOVA, analysis of variance; EEG, electroencephalography; ERP, event-related potential; FFT, fast Fourier transform; FL, frontal left; FR, frontal right; MMN, mismatch negativity; MMR, mismatch response; RM, repeated measures; SSEP, steady-state evoked potential. signals of music (Brett & Grahn, 2007;Drake et al., 2000;Fitch & Rosenfeld, 2007;Jacoby & McDermott, 2017;Kotz et al., 2018;Large & Palmer, 2002;Merchant et al., 2015;Merchant & Honing, 2014;Nettl, 2000;Ravignani et al., 2014) and speech (Buiatti et al., 2009;Chait et al., 2015;Ding et al., 2016;Giraud & Poeppel, 2012;Lerner et al., 2011;Liberman & Prince, 1977;C. ...
Article
From auditory rhythm patterns, listeners extract the underlying steady beat, and perceptually group beats to form meters. While previous studies show infants discriminate different auditory meters, it remains unknown whether they can maintain (imagine) a metrical interpretation of an ambiguous rhythm through top‐down processes. We investigated this via electroencephalographic mismatch responses. We primed 6‐month‐old infants (N = 24) to hear a 6‐beat ambiguous rhythm either in duple meter (n = 13), or in triple meter (n = 11) through loudness accents either on every second or every third beat. Periods of priming were inserted before sequences of the ambiguous unaccented rhythm. To elicit mismatch responses, occasional pitch deviants occurred on either beat 4 (strong beat in triple meter; weak in duple) or beat 5 (strong in duple; weak in triple) of the unaccented trials. At frontal left sites, we found a significant interaction between beat and priming group in the predicted direction. Post‐hoc analyses showed mismatch response amplitudes were significantly larger for beat 5 in the duple‐ than triple‐primed group (p = .047) and were non‐significantly larger for beat 4 in the triple‐ than duple‐primed group. Further, amplitudes were generally larger in infants with musically experienced parents. At frontal right sites, mismatch responses were generally larger for those in the duple compared to triple group, which may reflect a processing advantage for duple meter. These results indicate infants can impose a top‐down, internally generated meter on ambiguous auditory rhythms, an ability that would aid early language and music learning.
... Our lives are defined by rhythms of different frequencies: daily, weekly, seasonal, and annual, among others. The most prominent rhythms in our lives are rooted in the day-night cycle 1 . From biological cell functions to social activities and interactions, many aspects of human lives follow diurnal rhythms 2 . ...
Article
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Human activities follow daily, weekly, and seasonal rhythms. The emergence of these rhythms is related to physiology and natural cycles as well as social constructs. The human body and its biological functions undergo near 24-h rhythms (circadian rhythms). While their frequencies are similar across people, their phases differ. In the chronobiology literature, people are categorized into morning-type, evening-type, and intermediate-type groups called chronotypes based on their tendency to sleep at different times of day. Typically, this typology builds on carefully designed questionnaires or manually crafted features of time series data on people’s activity. Here, we introduce a method where time-stamped data from smartphones are decomposed into components using non-negative matrix factorization. The method does not require any predetermined assumptions about the typical times of sleep or activity: the results are fully context-dependent and determined by the most prominent features of the activity data. We demonstrate our method by applying it to a dataset of mobile phone screen usage logs of 400 university students, collected over a year. We find four emergent temporal components: morning activity, night activity, evening activity and activity at noon. Individual behavior can be reduced to weights on these four components. We do not observe any clear categories of people based on the weights, but individuals are rather placed on a continuous spectrum according to the timings of their phone activities. High weights for the morning and night components strongly correlate with sleep and wake-up times. Our work points towards a data-driven way of characterizing people based on their full daily and weekly rhythms of activity and behavior, instead of only focusing on the timing of their sleeping periods.
... Cognitive impairments lead to real-world disability and are a primary indicator of functional disability. The prime interest in neuropsychiatric medicine is to elucidate the mechanisms that give rise to such impairments and to establish successful therapies (Foster et al 2014) Light does have major effects on the organism and has the power to change circadian rhythms, as well as have effects on the nervous system and the body's ability to control its temperature. It may influence sleep cycles and produce cognitive effects (Foster et al 2005). ...
... Process S and Process C interact to promote sleep onset when sleep pressure is highest and circadian timing for arousal is low. Research on the neurobiological underpinnings of the two-process model is ongoing, but current evidence suggests that Process S is linked to the accumulation of certain molecules including adenosine in the brain [6] and that Process C is primarily controlled by the suprachiasmatic nuclei, a collection of neurons in the anterior hypothalamus [7]. ...
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Purpose of Review This review summarizes recent literature on the heritability of sleep and sleep disorders in childhood and adolescence. We also identify gaps in the literature and priorities for future research. Recent Findings Findings indicate that age, measurement method, reporter, and timing of sleep measurements can influence heritability estimates. Recent genome-wide association studies (GWAS) have identified differences in the heritability of sleep problems when ancestral differences are considered, but sample sizes are small compared to adult GWAS. Most studies focus on sleep variables in the full range rather than on disorder. Studies using objective measures of sleep typically comprised small samples. Summary Current evidence demonstrates a wide range of heritability estimates across sleep phenotypes in childhood and adolescence, but research in larger samples, particularly using objective sleep measures and GWAS, is needed. Further understanding of environmental mechanisms and the interaction between genes and environment is key for future research.
... Therefore, slope influences the road characteristics directly, which is an effective factor for driver alertness [64]. Alertness is controlled by the body clock and has different levels at different times of day [103]. Therefore, the time of day was an essential feature in this modeling. ...
Article
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Drivers’ lack of alertness is one of the main reasons for fatal road traffic accidents (RTA) in Iran. Accident-risk mapping with machine learning algorithms in the geographic information system (GIS) platform is a suitable approach for investigating the occurrence risk of these accidents by analyzing the role of effective factors. This approach helps to identify the high-risk areas even in unnoticed and remote places and prioritizes accident-prone locations. This paper aimed to evaluate tuned machine learning algorithms of bagged decision trees (BDTs), extra trees (ETs), and random forest (RF) in accident-risk mapping caused by drivers’ lack of alertness (due to drowsiness, fatigue, and reduced attention) at a national scale of Iran roads. Accident points and eight effective criteria, namely distance to the city, distance to the gas station, land use/cover, road structure, road type, time of day, traffic direction, and slope, were applied in modeling, using GIS. The time factor was utilized to represent drivers’ varied alertness levels. The accident dataset included 4399 RTA records from March 2017 to March 2019. The performance of all models was cross-validated with five-folds and tree metrics of mean absolute error, mean squared error, and area under the curve of the receiver operating characteristic (ROC-AUC). The results of cross-validation showed that BDT and RF performance with an AUC of 0.846 were slightly more accurate than ET with an AUC of 0.827. The importance of modeling features was assessed by using the Gini index, and the results revealed that the road type, distance to the city, distance to the gas station, slope, and time of day were the most important, while land use/cover, traffic direction, and road structure were the least important. The proposed approach can be improved by applying the traffic volume in modeling and helps decision-makers take necessary actions by identifying important factors on road safety.
... Exposure to artificial light (which is now possible at any time during the day), shift work, jet lag, and various lifestyle options (night-time working, eating, or engaging in various social activities) may cause repeated endogenous circadian clock changes that can have a negative impact on human life. The consequences include oxidative stress, inflammation (an increase in inflammatory markers including IL-6, C-reactive protein, and TNF-α), and loss of synapses [75][76][77]. ...
Article
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Stroke occurrence is not randomly distributed over time but has circadian rhythmicity with the highest frequency of onset in the morning hours. This specific temporal pattern is valid for all subtypes of cerebral infarction and intracerebral hemorrhage. It also correlates with the circadian variation of some exogenous factors such as orthostatic changes, physical activity, sleep-awake cycle, as well as with endogenous factors including dipping patterns of blood pressure, or morning prothrombotic and hypofibrinolytic states with underlying cyclic changes in the autonomous system and humoral activity. Since the internal clock is responsible for these circadian biological changes, its disruption may increase the risk of stroke occurrence and influence neuronal susceptibility to injury and neurorehabilitation. This review aims to summarize the literature data on the circadian variation of cerebrovascular events according to physiological, cellular, and molecular circadian changes, to survey the available information on the chronotherapy and chronoprophylaxis of stroke and its risk factors, as well as to discuss the less reviewed impact of the circadian rhythm in stroke onset on patient outcome and functional status after stroke.
... Circadian clocks have proven to be particularly important for human physiology adapted to the light-dark cycle of 24 h, so that a person's sleep habits, eating patterns and diet can desynchronize the body's clocks and can contribute to the onset of non-communicable diseases [245,246]. ...
Article
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In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.
... Disruption of circadian rhythm is closely related to stressors. Repeated or long-term exposure to stressors may contribute to the development of mental illness or metabolism in rodents and humans and can result to long-lasting adaptations, such as energy metabolism [5,6]. Stressors are vital to the characteristics of the stress response. ...
Chapter
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Our lives are dominated by circadian rhythms (which last about a whole day), most notably through the sleep-wake cycle. Almost all important physiological and metabolic processes are controlled by circadian rhythms. The ability to predict day-night changes in the environment gives most species on earth an evolutionary advantage. As a result, from plants to higher mammals, organisms form endogenous biological clocks in order to adapt to circadian rhythm changes. In the absence of external time indicators, the internal clock can automatically run on a cycle of about 24 h. Stress responses begin with a local physical (such as skeletal muscle contusion) or mental (such as loss of a loved one) stressor but always end up with a broad, systematic process of response that affects many organs and systems. It is normal, then, that disorders of circadian rhythm put the body in a state of stress that leads to various mental, neurological, and metabolic disorders.
... Your body is telling you that it's time to sleep however, outside the sun is rising. [4] Jet lag isn't a badge of honour, which would make travellers feel proud. Instead, it's a significant modern problem. ...
Article
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It's the most exciting thing to move around from one section of the globe to the other part, swiftly. However, Jet lag is the most frustrating component of such long journeys. Jet lag happens when our internal clock is desynchronized by travelling across several time zones in a short time. Jet lag is not a badge of honour, but a significant modern problem. Hence, it's worth understanding the means to handle Jet lag without counting on sleeping pills. Melatonin has proven to be a better and safer treatment for Jet lag. This review is a general topic of interest and talks over the causes, and implications of Jet lag. It also gives special emphasis on the method to use judiciously timed exogenous melatonin to conquer the jet lag.
... In fact, most people who suffer from mood disorders are shown to have significant disruptions in their circadian rhythms and the sleep/wake cycle [25][26][27]. Environmental disruptions to circadian rhythms such as shift work, travel across time zones, and altered sleep-wake cycles tend to have strong effects on mood and mental illness [28][29][30]. There could be more than one way in which circadian disruption affects mood. ...
Article
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The idea that light affects mood and behavioral state is not new. However, not much is known about the particular mechanisms and circuits involved. To fully understand these, we need to know what properties of light are important for mediating changes in mood as well as what photoreceptors and pathways are responsible. Increasing evidence from both human and animal studies imply that a specialized class of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), plays an important role in the light-regulated effects on mood and behavioral state, which is in line with their well-established roles in other non-visual responses (pupillary light reflex and circadian photoentrainment). This paper reviews our current understanding on the mechanisms and paths by which the light information modulates behavioral state and mood.
Preprint
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Social attention is fundamental to a wide range of behaviours in non-human primates. However, we know very little about the heritability of social attention in non-human primates, and the heritability of attention to social threat has not been assessed. Here, we provide data to begin to fill this gap in knowledge. We tested 67 female rhesus macaques, Macaca mulatta, on an attention bias preferential looking task in which they viewed threat-neutral face pairs. We recorded a number of looking time measures of social attention to conspecific faces, and attention to conspecific threat faces specifically. In addition, we recorded levels of vigilant scanning in the social group. We quantified heritability and maternal effects using pedigree information. Repeatabilities for social attention ranged from 11% - 25%. Repeatability for attention to threat faces was 16%, with zero repeatability for attention bias, calculated by subtracting duration of looking towards the neutral face from duration of looking towards the threat face (a common practice in the literature). Heritabilities for social attention were 8% - 14%, with maternal effects 6% - 11%. Heritability for attention to threat was 10%, with maternal effect 4%. This is the first study that we are aware of to test the heritability of attention to threat in a non-human primate. We discuss these findings in light of understanding mechanisms underlying social behaviour in primates, evolutionary pathways of social attention in humans, epidemiology of mental health issues such as anxiety, and potential for improving markers of animal emotion and wellbeing in captivity.
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The Nobel Prize in Physiology or Medicine 2017 was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm”. Our body clocks control metabolism, contributing to the proper functioning of every organ in our bodies. The light/dark cycle is the main marker of our circadian rhythms. If we don’t use the right light at the right moment our body clocks become disoriented and stop functioning correctly. And this is what happens when we disrupt the circadian systems of patients in hospitals being in ICU or rooms by means of using the wrong light in a given moment. Many peer-reviewed researches in healthcare buildings, has demonstrated that access to daylight provides: reduction in the average length of hospital stay, quicker post-operative recovery and reducing ICU delirium, as well as reduced requirements for pain relief.
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Circadian rhythms regulate several physiological functions and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle and apoptosis. Few studies have investigated the role of those circadian genes in prostate cancer occurrence. We aim to investigate the relationship between circadian genes polymorphisms and prostate cancer risk based on data from the EPICAP study, a population‐based case‐control study including 1515 men (732 cases / 783 controls) with genotyped data. Odds Ratios (ORs) for association between prostate cancer and circadian gene variants were estimated for each of the 872 single nucleotide polymorphisms (SNPs) in 31 circadian clock genes. We also used a gene‐based and pathway‐based approach with a focus on the pathway including 9 core circadian genes. Separate analyses were conducted by prostate cancer aggressiveness. The core‐circadian pathway (P=0.0006) was significantly associated to prostate cancer, for either low (P=0.002) or high (P=0.01) grade tumour. At the gene level, we observed significant associations between all prostate cancer and NPAS2 and PER1 after correcting for multiple testing, while only RORA was significant for aggressive tumors. At the SNP‐level, no significant association was observed. Our findings provide additional evidence of a potential link between genetic variants in circadian genes and prostate cancer risk. Further investigation is warranted to confirm these findings and to better understand the biological pathways involved. This article is protected by copyright. All rights reserved.
Chapter
Phenoptosis describes ageing as the evolved product of a genome‐based program to limit lifespan and thereby favour evolution. Previously, programmed ageing was deemed incompatible with Darwinian dogma that population evolution depends upon genetic diversity resulting from selection of traits that provide individual benefit. To avoid this conflict, phenoptosis employs evolvability, an alternative theory of evolution through which biological systems can acquire novel functions that enhance population evolution without individual benefit. This article analyses the claim that ‘programmed’ ageing evolved de novo, specifically to limit lifespan exclusively under the cloak of evolvability, and if certain assumptions in phenoptosis theory are valid. A brief historic perspective of its origins will be followed by considerations of ‘when’, ‘why’ and ‘how’ it evolved. An alternative ‘programmatic’ theory that presents a mechanism for the coincidental evolution of ageing with the developmental program will be compared and contrasted with phenoptosis. Key Concepts • Individual benefit is incompatible with phenoptosis (programmed ageing) theory, but compatible with development/ageing continuum (programmatic ageing) theory. • Immortal/nonageing animals preceded the evolution of phenoptosis. • Phenoptosis relies exclusively upon ‘evolvability’ to explain the evolution of ageing, yet ageing promotes ‘evolvability’ thereafter. • In nonsenescing populations (presumably existing before phenoptosis), evolution would be stifled by low adult death rate. • Natural selection in immortal populations causes unchecked birth rates, overpopulation and subsequent extinctions. Phenoptosis then emerges as an adaptation. • Phenoptosis evolved by the process of ‘supra‐individual’ selection. • Selection for ecological homeostasis counterbalances selection for expanding individual reproductive fitness and keeps growth rates in check. • Scheduled death increases individual turnover, provides more chances for evolution of diverse genotypes and thereby, increases evolvability. • Programmatic ageing is a product of coincidental evolution resulting from post‐maturational decay of the developmental program and of second‐order selection for population benefit. • Ageing is initiated and accelerated by progressive loss of temporal organisation within the whole organism, not by any individual or few factors affecting single metabolic or physiologic functions.
Article
Indoor lighting is known to affect people’s wellbeing, mood and behaviour. The rapid development of new energy-efficient lamp technologies has enabled new lighting applications in home environments. To investigate the prospects of introducing a personalised light emitting diode (LED)-based home lighting technology, a mixed-methods research study was carried out, applying the goal-framing theory. The results, based on a questionnaire survey (N = 536), show that purchasing costs of energy-efficient lamps have little effect on consumers’ lamp choices, and that the degree of consumer acceptance of LED lamps has increased in recent years without resulting in increased lighting use. The results confirm that Swedish homes are characterised by many lamps, an average of 39 per home, but there is a significant variation across tenure type. Based on a qualitative analysis of interviews with 12 participants, the conclusion can be drawn that residents seem to know what kind of lighting they want, but they do not necessarily have what they want for a variety of reasons. Besides individual characteristics, situational factors influence residents’ home lighting and visual comfort, such as the indoor built home environment and the availability of lighting products. Consequently, responsibility for residents’ actual home lighting also lies with housing developers, lighting producers and providers.
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This paper discusses the effect of chrononutrition on the regulation of circadian rhythms; in particular, that of chocolate on the resynchronization of the human internal biological central and peripheral clocks with the main external synchronizers, light–dark cycle and nutrition-fasting cycle. The desynchronization of internal clocks with external synchronizers, which is so frequent in our modern society due to the tight rhythms imposed by work, social life, and technology, has a negative impact on our psycho-physical performance, well-being, and health. Taking small amounts of chocolate, in the morning at breakfast at the onset of the active phase, helps speed up resynchronization time. The high flavonoid contents in chocolate promote cardioprotection, metabolic regulation, neuroprotection, and neuromodulation with direct actions on brain function, neurogenesis, angiogenesis, and mood. Although the mechanisms of action of chocolate compounds on brain function and mood as well as on the regulation of circadian rhythms have yet to be fully understood, data from the literature currently available seem to agree in suggesting that chocolate intake, in compliance with chrononutrition, could be a strategy to reduce the negative effects of desynchronization. This strategy appears to be easily implemented in different age groups to improve work ability and daily life.
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Promoting resource- and energy-efficient home lighting through technology and behaviour change requires an understanding of how residents currently use lighting and what they want from it. However, users' needs and desires relating to lighting in homes are poorly understood, as research is still limited. This paper aims to provide a fuller picture of residents' experiences with their home lighting. Interviews about how residents perceive the character of lighting and luminaires and lighting use suggest that home lighting has nine capabilities: to enable vision; to facilitate visual tasks; to display objects; to send a message; to support a particular atmosphere; to shape the architectural space; to offer a visual aesthetic experience; to maintain or change rhythmicity; and to evoke memories. Secondary data confirmed five of them. The identified capabilities relate to behavioural goals, psychological wellbeing and social needs. We conclude that seemingly wasted light in people's homes, i.e. lights left on in unoccupied rooms, can serve a purpose for the residents, such as avoiding visual or aesthetic discomfort, making the home inviting, benefitting people outside and providing safety. Findings have implications for the further development of new lighting technologies and design, energy-saving campaigns targeting residents and for urban outdoor environments.
Article
At the core of human thought, for the majority of individuals in the developed nations at least, there is the tacit assumption that as a species we are unfettered by the demands imposed by our biology and that we can do what we want, at whatever time we choose, whereas in reality every aspect of our physiology and behaviour is constrained by a 24 h beat arising from deep within our evolution. Our daily circadian rhythms and sleep/wake cycle allow us to function optimally in a dynamic world, adjusting our biology to the demands imposed by the day/night cycle. The themes developed in this review focus upon the growing realization that we ignore the circadian and sleep systems at our peril, and this paper considers the mechanisms that generate and regulate circadian and sleep systems; what happens mechanistically when these systems collapse as a result of societal pressures and disease; how sleep disruption and stress are linked; why sleep disruption and mental illness invariably occur together; and how individuals and employers can attempt to mitigate some of the problems associated with working against our internal temporal biology. While some of the health costs of sleep disruption can be reduced, in the short-term at least, there will always be significant negative consequences associated with shift work and sleep loss. With this in mind, society needs to address this issue and decide when the consequences of sleep disruption are justified in the workplace.
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Özet: Çalışma zamanı ve süresi, çalışanların günlük hayatını ve psikolojik halini etkileyen bir değişken olarak karşımıza çıkmak-tadır. Günümüzde çalışma hayatının getirdiği yükler, çalışma düzen-lerindeki değişimler, çalışma süresi ve yoğunluğundaki yükselme ile maddi ihtiyaç ve beklentilerdeki artışlarla birlikte gece çalışmaları ve vardiyalarının insan psikolojisi üzerindeki etkisi de gittikçe artış gös-termektedir. Bu durumun yanı sıra iş sağlığı, iş hukuku, ceza hukuku ve çalışma psikolojisi alanlarındaki gelişmeler, çalışanların iş hayatı ile sağlığı arasındaki ilişkinin incelenmesi açısından büyük değer ta-şımaktadır. Abstract: Working time and working hours are considered as a variable that affects employees' daily lives and psychological states. Nowadays the burdens of working life together with the changes of work order, increases in working hours and intensity, the rise of financial needs and expectations, the effects of night works and shifts on human psychology show gradual increase. Apart from this situation improvements in the areas of occupational health, labour law, criminal law and psychology of working have great importance in terms of studying the relationship between employees' working life and health.
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Chapter
It is universally accepted that a good night's sleep is important for individuals to feel refreshed and energised. However, some patients struggle to achieve sufficient amounts of good quality rest, which can adversely impact their health and well-being. This chapter considers the physiology of sleep, its role in disease and provides patient-centred advice about how to improve sleep quality and quantity.
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Alteration of day and night is one of the essential circadian rhythms that build the phenomenon of sleep/wake in humans and other animals. Daily rhythms impact different individuals differently. Light exposure and an individual's circadian response are two aspects that create diversity in phenotype. These diverse phenotypes are called chronotypes. Chronotype varies over the life history stages. Chronotype is seen as morning type in children, evening type in adolescents, and again reverts back to the morning type in adults and old-aged individuals. It is observed that adolescents being evening types have bedtime later in com-parison to children and adults. Adolescent physiology/ body clock does not allow them to sleep early and school routine/social clock does not let them sleep till late. Thus, their night phase is shrunk and sleep hours are reduced, which hinders their day-time functioning, including mental tasks such as cognition, learning and memory-based exercises, and physical tasks such as physical presence during field and athletic events. These days sleep debt is a critical health concern in the adolescent popula-tion. The current review focuses on the adolescent sleep-needs and various factors affecting their healthy sleep. This also en-compasses the understanding of biological clocks, their misalignment, disrupters, causes and impact. The present study would be helpful in finding out the difference between the biological clock and social clock of the adolescent population, elaborates the need for sleep education and suggests a solution to this alarming problem of sleep debt in teens.
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Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
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Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
Article
Circadian rhythms have received increasing attention within the context of mental disorders. Evening chronotype has been associated with enhanced risk to develop anxiety and post-traumatic stress disorder (PTSD). The classical fear conditioning paradigm is a powerful tool to reveal key mechanisms of anxiety and PTSD. We used this paradigm to study the neurocognitive basis of the association between chronotype and fear responses in healthy humans. 20 participants with evening chronotype and 20 controls (i.e., intermediate chronotype) completed a 2-day Pavlovian fear learning and extinction virtual reality task. Participants received fear conditioning, and extinction learning on day 1. Extinction memory recall was tested on day 2. To address interactions between chronotype and time of day of the fear conditioning, and extinction performance, half of the participants were tested in the morning, and the other half in the evening. Skin conductance response (SCR) and subjective fear ratings were measured as primary outcomes. Chronotype was established via the morningness–eveningness questionnaire (MEQ-SA). We found an overall higher SCR for fear acquisition in participants with the evening chronotype profile, compared to controls. Moreover, the higher the MEQ-SA scores –indicative of less eveningness – the lower the SCR was. No effects of chronotype were found for extinction and extinction recall. The higher vulnerability of the evening chronotype for anxiety and related disorders may thus be explained by enhanced fear acquisition of this group.
Book
In this groundbreaking text, Youdell and Lindley bring together cutting-edge research from the fields of biology and social science to explore the complex interactions between the diverse processes which impact on education and learning. Transforming the way we think about our students, our classrooms, teaching and learning, Biosocial Education draws on advances in genetics and metabolomics, epigenetics, biochemistry and neuroscience, to illustrate how new understandings of how bodies function can and must inform educational theory, policy and everyday pedagogical practices. Offering detailed insight into new findings in these areas and providing a compelling account of both the implications and limits of this new-found knowledge, the text confronts the mechanisms of interaction between multiple biological and social factors, and explores how educators might mobilize these 'biosocial' influences to enhance learning and enable each child to attain educational success. By seeking out transdisciplinary and multi-factor answers to the question of how education works and how children learn, this book lays the foundations for a step-change in the way we approach learning. It is an essential read for researchers, teachers and practitioners involved in educational policy and practice at any level. © 2019 Deborah Youdell and Martin R. Lindley. All rights reserved.
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Sleep and circadian rhythm disruption (SCRD) and schizophrenia are often co-morbid. Here, we propose that the co-morbidity of these disorders stems from the involvement of common brain mechanisms. We summarise recent clinical evidence that supports this hypothesis, including the observation that the treatment of SCRD leads to improvements in both the sleep quality and psychiatric symptoms of schizophrenia patients. Moreover, many SCRD-associated pathologies, such as impaired cognitive performance, are routinely observed in schizophrenia. We suggest that these associations can be explored at a mechanistic level by using animal models. Specifically, we predict that SCRD should be observed in schizophrenia-relevant mouse models. There is a rapidly accumulating body of evidence which supports this prediction, as summarised in this review. In light of these emerging data, we highlight other models which warrant investigation, and address the potential challenges associated with modelling schizophrenia and SCRD in rodents. Our view is that an understanding of the mechanistic overlap between SCRD and schizophrenia will ultimately lead to novel treatment approaches, which will not only ameliorate SCRD in schizophrenia patients, but also will improve their broader health problems and overall quality of life.
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To evaluate whether depressive symptom severity leads to poorer response and perceived adherence to cognitive behavioral therapy for insomnia (CBTI) and to examine the impact of CBTI on well-being, depressive symptom severity, and suicidal ideation. Pre- to posttreatment case replication series comparing low depression (LowDep) and high depression (HiDep) groups (based on a cutoff of 14 on the Beck Depression Inventory [BDI]). 127 men and 174 women referred for the treatment of insomnia. Seven sessions of group CBTI. Improvement in the insomnia severity, perceived energy, productivity, self-esteem, other aspects of wellbeing, and overall treatment satisfaction did not differ between the HiDep and LowDep groups (p > 0.14). HiDep patients reported lower adherence to a fixed rise time, restricting time in bed, and changing expectations about sleep (p < 0.05). HiDep participants experienced significant reductions in BDI, after removing the sleep item. Levels of suicidal ideation dropped significantly among patients with pretreatment elevations (p < 0.0001). Results suggest that pre- to post CBTI improvements in insomnia symptoms, perceived energy, productivity, self-esteem, and other aspects of well-being were similar among patients with and without elevation in depressive symptom severity. Thus, the benefits of CBTI extend beyond insomnia and include improvements in non-sleep outcomes, such as overall well-being and depressive symptom severity, including suicidal ideation, among patients with baseline elevations. Results identify aspects of CBTI that may merit additional attention to further improve outcomes among patients with insomnia and elevated depressive symptom severity.
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Insomnia is a putative causal factor for persecutory thinking. Recent epidemiological studies show a strong association of insomnia and paranoia. The clinical implication is that reducing insomnia will reduce paranoid delusions. This study, evaluating for the first time the treatment of insomnia in individuals with persecutory delusions, provides a test of this hypothesis. It was predicted that a brief cognitive behavioural intervention for insomnia (CBT-I) for individuals with persistent persecutory delusions and sleep difficulties would not only reduce the insomnia but that it would also reduce the paranoia. Fifteen patients with persistent persecutory delusions and insomnia in the context of a psychotic disorder were each individually given a standard-format, four-session CBT-I intervention. Outcome assessments were conducted at pre-treatment, post-treatment and one-month follow-up. There were no missing data. Following the intervention, significant reductions were found in levels of insomnia and the persecutory delusions. The effect sizes were large, and the changes were maintained at the follow-up. At least two-thirds of participants made substantial improvements in insomnia and approximately half showed substantial reductions in the persecutory delusions. There were also reductions in levels of anomalies of experience, anxiety and depression. The main limitations are the absence of a control group and unblinded assessments. A more methodologically rigorous evaluation of this intervention is now warranted. These preliminary findings suggest that CBT-I can be used to treat insomnia in individuals with persecutory delusions and that, consistent with the hypothesised causal role, it also lessens the delusions.
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Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs.
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Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.
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Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.
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Circadian rhythms are ∼24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional–translational autoregulatory loop generates molecular oscillations of ‘clock genes’ at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.
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As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus ( approximately 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light.
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Why can't teenagers get out of bed in the morning? How do bees tell the time? Why do some plants open and close their flowers at the same time each day? Why do so many people suffer the misery of jet lag? In this fascinating book, Russell Foster and Leon Kreitzman explain the significance of the biological clock, showing how it has played an essential role in evolution and why it continues to play a vitally important role in all living organisms. The authors tell us that biological clocks are embedded in our genes and reset at sunrise and sunset each day to link astronomical time with an organism's internal time. They discuss how scientists are working out the clockwork mechanisms and what governs them, and they describe how organisms measure different intervals of time, how they are adapted to various cycles, and how light coordinates the time within to the external world. They review problems that can be caused by malfunctioning biological clocks-including jet lag, seasonal affective disorder, and depression. And they warn that although new drugs are being promoted to allow us to stay awake for longer periods, a 24/7 lifestyle can have a harmful impact on our health, both as individuals and as a society. © 2004, 2005 by Russell G. Foster and Leon Kreitzman. All rights reserved.
Book
Early Birds and night owls are born, not made. Sleep patterns may be the most obvious manifestation of the highly individualized biological clocks we inherit, but these clocks also regulate bodily functions from digestion to hormone levels to cognition. Living at odds with our internal timepieces. Till Roenneberg shows, can make us chronically sleep deprived and more likely to smoke, gain weight, feel depressed, fall ill, and fail geometry. By understanding and respecting our internal time, we can live better. This book combines storytelling with accessible science tutorials to explain how our internal clocks work---for example, why morning classes are so unpopular and why "lazy" adolescents are wise to avoid them. We learn why the constant twilight of our largely indoor lives makes us dependent on alarm clocks and tired, and why social demands and work schedules lead to a social jet lag that compromises our daily functioning. Many of the factors that make us early or late "chronotypes" are beyond our control, but that doesn't make us powerless. Roenneberg recommends that the best way to sync our internal time with our external environment and feel better is to get more sunlight. Such simple steps as cycling to work and eating breakfast outside may be the tickets to a good night's sleep, better overall health, and less grouchiness in the morning. (PsycINFO Database Record (c) 2012 APA, all rights reserved)(jacket)
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Severely disturbed sleep is known to occur during and shortly prior to the onset of mood episodes in bipolar disorder. Whether alterations in sleep occur parallel and as part of the disease process or whether they represent a trait existent before the onset of the disorder itself remains unclear. A systematic review evaluating all published data on the occurrence of disordered sleep prior to the onset of the first mood episode was conducted. The evidence cited within this paper suggests that sleep disturbances frequently precede bipolar disorder by several years and convey an elevated long-term risk for developing any kind of mood disorder. Disordered sleep appears to emerge about the time of puberty and remains persistently elevated in individuals at high risk. Disturbed sleep appears to be an early symptom of bipolar disorder but further research, especially longitudinal studies in individuals at high risk, will be required to characterize the type and patterns more precisely.
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A reduction in sleep amount from late childhood through the second decade has long been known; however, the weight of current evidence holds that sleep need does not decline across this span. This article will describe how the loss of sleep through adolescence is not driven by lower need for sleep but arises from a convergence of biologic, psychological, and socio-cultural influences.
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Numerous lines of evidence suggest that a disordered circadian system contributes to the etiology and symptomatology of major psychiatric disorders. Sleep disturbances, particularly rapid eye movement (REM) sleep, have been observed in bipolar affective disorder (BPD) and schizophrenia. Therapies aimed at altering the timing and duration of sleep and realigning circadian rhythms, including sleep scheduling, wake extension, light therapy and drug therapies that alter sleep and circadian rhythms appear beneficial for affective disorders. Interventional studies aiming to correct sleep and circadian disturbances in schizophrenia are scarce, although exogenous melatonin has been shown to improve both sleep structure and psychotic symptoms. The study of molecular clock mechanisms in psychiatric disorders is also gaining interest. Genetics studies have found associations with CLOCK, PERIOD1, PERIOD3, and TIMELESS in schizophrenia. Most research on BPD has focused on polymorphisms of CLOCK, but the lithium target GSK-3 may also be significant. New research examining the role of circadian rhythms and clock genes in major mental illness is likely to produce rapid advances in circadian-based therapeutics.
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Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses, circadian rhythms expressed by neurons in the same culture are not synchronized. After reversible blockade of neuronal firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered phases. These data suggest that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them.
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We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.
Why teenagers really do need an extra hour in bed
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Making Waves: Irving Dardik and His Superwave Principle
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Lewin R (2005). Making Waves: Irving Dardik and His Superwave Principle. Rodale, Emmaus, PA, USA.
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