Shiftwork-Mediated Disruptions of Circadian Rhythms and Sleep Homeostasis Cause Serious Health Problems (original) (raw)
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Sleep interruption associated with house staff work schedules alters circadian gene expression
Sleep Medicine, 2015
Background-Epidemiological studies indicate that disruption of circadian rhythm by shift work increases the risk of breast and prostate cancer. Our studies demonstrated that carcinogens disrupt the circadian expression of circadian genes (CGs) and circadian-controlled genes (CCGs) during the early stages of rat mammary carcinogenesis. A chemopreventive regimen of methylselenocysteine (MSC) restored the circadian expression of CGs and CCGs, including PERIOD 2 (PER2) and estrogen receptor β (ERS2), to normal. The present study evaluated whether changes in CG and CCG expression in whole blood can serve as indicators of circadian disruption in shift workers. Methods-Fifteen shift workers were recruited to a crossover study. Blood samples were drawn before (6 PM) and after (8 AM) completing a night shift after at least 7 days on floating night-shift rotation, and before (8 AM), during (1 PM), and after (6 PM) completing 7 days on day shift. The plasma melatonin level and messenger RNA (mRNA) expression of PER2, nuclear receptor subfamily 1, group d, member 1 (NR1D1), and ERS2 were measured, and the changes in levels of melatonin and gene expression were evaluated with statistical analyses.
The genetics of circadian rhythms, sleep and health
Human Molecular Genetics, 2017
Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and psychiatric illness including depression (1,2). Mouse models of clock mutants recapitulate these deficits, implicating mechanistic and causal links between SCRD and disease pathophysiology (3-5). Importantly, treating clock disruption reverses and attenuates these adverse health states in animal models (6,7), thus establishing the circadian system as a novel therapeutic target. Significantly, circadian and clock-controlled gene mutations have recently been identified by Genome-Wide Association Studies (GWAS) in the aetiology of sleep, mental health and metabolic disorders. This review will focus upon the genetics of circadian rhythms in sleep and health.
International Journal of Environmental Research and Public Health
Background: The effect of circadian disruption on the bio-psychological clock system has been widely studied. However, the mechanism and the association of circadian rhythm disruption with mental health and physiological responses are still unclear. Therefore, this study was conducted to investigate the effects of circadian rhythm disruption on mental health and physiological responses among shift workers and the general population. Methods: A total of 42 subjects participated in this quasi-experimental study. Participants were divided into a group of shift workers (n = 20) and a general population group (n = 22). Polysomnography tests, blood tests (cortisol, triglycerides and glucose), and psychological tests (Abbreviated Profile of Mood States, General Health Questionnaire-28, Working Memory and Processing Speed Indexes of the Wechsler Adult Intelligent Scale (WAIS-IV) were used to examine the effects of circadian rhythm disruption. Results: The results showed a significant relati...
Sleep, 2007
This the first of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. In this first part of this paper, the general principles of circadian biology that underlie clinical evaluation and treatment are reviewed. We then report on the accumulated evidence regarding the evaluation and treatment of shift work disorder (SWD) and jet lag disorder (JLD). A set of specific questions relevant to clinical practice were formulated, a systematic literature search was performed, and relevant articles were abstracted and graded. A substantial body of literature has accumulated that provides a rational basis the evaluation and treatment of SWD and JLD. Physiological assessment has involved determination of circadian phase using core body temperature and the timing of melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy and the Morningness-Eveningn...
Background. Epidemiologic evidence indicates that sleep loss may be a novel risk factor for cardiovascular diseases (CVDs); hypertension, coronary artery disease (CAD) and stroke. The increased risk of CVDs is possibly linked to the effect of sleep loss on hormones that play a major role in the central control of blood pressure and heart rate variability, also on angiotensin, cytokines, appetite and energy expenditure as well as sympathetic and vagal activity, melatonin and serotonin. Methods. Internet search and expert opinion from colleagues. Results. Exposure to light at night disturbs the circadian system with alterations of the sleep/activity patterns and suppression of melatonin production. Light is the most powerful synchronizer but, when exposure occurs at a time when the body would normally not be exposed to light, (that is, at night), then it disrupts the circadian rhythms. In developed countries, approximately, one fifth of the workers may have disruption of sleep due to night shift and may be unable to tolerate exposure to light during this time. Daily physiological variations include normal circadian rhythms which are interactive and require a high degree of phase positioning to produce subjective feelings of well being. Disturbances in these activities, may predispose circadian desynchronization, (whether from passage over time zones or from shift rotation), resulting in disturbance of the quantity and quality of sleep leading to hormonal and cardiovascular dysfunction. Shift work can increase the risk of CVD by several interrelated psychosocial, behavioral, and physiological mechanisms. Biological mechanisms are related to the activation of the autonomic nervous system, inflammation, dyslipidemia and glucose intolerance, which may increase the risk for atherosclerosis, metabolic syndrome and insulin resistance resulting in CAD, hypertension and stroke. It is important to promote greater changes in behavioural factors like physical activity, Mediterranean-style diet and meditation apart from providing rotation in shift to cover the loss of sleep. Conclusions. Disruption of sleep has become a public health problem due to industrialization and urbanization. Strategies to reduce the potential for circadian disruption, including extending the daily dark period, appreciating nocturnal awakening in the dark, using dim red light for R. B. Singh, B. Anjum, Rajiv Garg et al. 24 night-time necessities, and avoiding frequently rotating shifts. There is a need to have more intensive guidelines on dietary intakes, physical activity and meditation to prevent CVDs among subjects who have significant sleep disruption.
Circadian Rhythm Sleep Disorders: Part I, Basic Principles, Shift Work and Jet Lag Disorders
Sleep, 2007
Evotec and Cephalon and has participated in speaking engagements for World Class and Cephalon. Dr. Wright has received research support from and has participated in speaking engagements for Cephalon and Takeda, and has consulted for Takeda. Dr. Vitiello is on the speakers bureau for Takeda. Drs. Auger and Zhdanova have indicated no financial conflicts of interest.
Jet lag syndrome: circadian organization, pathophysiology, and management strategies
Nature and Science of Sleep, 2010
The circadian system regulates the cyclical occurrence of wakefulness and sleep through a series of oscillatory networks that comprise two different theoretical processes. The suprachiasmatic nucleus (SCN) of the hypothalamus contains the master oscillatory network necessary for coordinating these daily rhythms, and in addition to its ability to robustly generate rhythms, it can also synchronize to environmental light cues. During jet lag, abrupt shifts in the environmental light-dark cycle temporarily desynchronize the SCN and downstream oscillatory networks from each other, resulting in increased sleepiness and impaired daytime functioning. Polysomnographic data show that not only does jet lag result in changes of sleep-wake timing, but also in different aspects of sleep architecture. This type of circadian misalignment can further lead to a cluster of symptoms including major metabolic, cardiovascular, psychiatric, and neurological impairments. There are a number of treatment options for jet lag involving bright light exposure, melatonin, and use of hypnotics, but their efficacy greatly depends on their time of use, the length of time in the new time zone, and the specific circadian disturbance involved. The aim of this review is to provide mechanistic links between the fields of sleep and circadian rhythms to understand the biological basis of jet lag and to apply this information to clinical management strategies.