Impacts of shift work on sleep and circadian rhythms

Shift work comprises work schedules that extend beyond the typical “nine-to-five” workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2–5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers’ health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers’ impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts.     

Bright light affects human circadian rhythms

The relative effectiveness of external zeitgebers synchronizing circadian rhythms can be evaluated by mesuring the size of the range of entrainment. The experimental approach to measure entrainment limits is the application of an artificial zeitgeber with slowly and steadily changing period. In human circadian rhythms, an absolute light-dark (LD) cycle with a light intensity during L of 100 lux or less, results in an upper entrainment limit of 26.91±0.24 hours. The same limit is reached in constant illumination when only informations are given to the subjects. Consequently, the LD cycle is effective mainly with its behavioral component characterized by the request of the light-dark alternation to go to rest. In experiments with the same experimental protocol but higher intensity of illumination during L (400 lux, i.e., exceeding the threshold beyond which melatonin excretion is suppressed in humans), human circadian rhythms can be synchronized within a much larger range; the upper entrainment limit is, with all overt rhythms measured, beyond 29 hours. This means that bright light has an effect on the human circadian system which is qualitatively different from that of dim light, and which is similar to the effect of light in most animal experiments. This finding has theoretical and practical implications.     

The influence of day and night work on the circadian variations of cardiovascular performance

Summary Circadian variations of the pre-ejection period, Q-T interval, heart rate and oral temperature at rest and in day and night shift work were investigated. At rest, pronounced circadian variation was found in heart rate, pre-ejection period and Q-T interval. The ratio between Q-T interval and heart rate also shows a distinct circadian variation. When working, the rest rhythms of the variables were obscured. The physiological implications for shift work are discussed.Supported by the National Swedish Board for Technical Development, Grants No. 76-7096 I and 78-4307     

Use of bright light to treat maladaptation to night shift work and circadian rhythm sleep disorders

SUMMARY  Night work is associated with increased sleepiness and disturbed sleep. Maladaptation of the circadian system, which is phase-adjusted to day time work and thus promotes sleepiness during its nadir at night and wakefulness (or disturbed sleep) during the day, contributes substantially to this problem. A major cause of suboptimal circadian phase adjustment among night workers is the exposure to morning light, which prevents the delay needed for optimal adjustment to night work. Several laboratory studies indicate that careful application of bright light may cause the circadian system to shift to any desired phase. Furthermore, studies of simulated night work demonstrate that night exposure to bright light can virtually eliminate circadian maladjustment among night workers. While the results are promising, there is still, however, an urgent need for longitudinal studies of bright light application in. real-life settings.     

Alteration of period and amplitude of circadian rhythms in shift workers

Summary 48 male shift workers in various industries volunteered to document circadian rhythms in sleeping and working, oral temperature, grip strength of both hands, peak expiratory flow and heart rate. All physiological variables were selfmeasured 4 to 5 times a day for 2 to 4 weeks. Individual time series were analyzed according to several statistical methods (power spectrum, cosinor, chi squares, ANOVA, correlation, etc.) in order to estimate rhythm parameters such as circadian period () and amplitude (A), and to evaluate subgroup differences with regard to tolerance to shift work, age, duration of shift work, speed of rotation and type of industry. The present study confirms for oral temperature and extends to other variables (grip strength of both hands, heart rate) that intolerance to shift work is frequently associated with both internal desynchronization and small circadian amplitude. The internal desynchronization among several circadian rhythms supports the hypothesis that these latter are driven by several oscillators. Many differences were observed between circadian rhythms in right and left hand grip strength: circadian in oral temperature was correlated with that in the grip strength of the dominant hand but not with that of the other hand; changes in s of the non-dominant hand were age-related but did not correlate with temperature ; only the circadian A of the non-dominant hand was associated with a desynchronization. Thus, circadian rhythms in oral temperature and dominant hand grip strength may be driven by the same oscillator while that of the non-dominant hand may be governed by a different one. Internal desynchronization between both hand grip rhythms as well as desynchronization of performance rhythms reported by others provide indirect evidence that circadian oscillator(s) may be located in the human cerebral cortex.     

An hour of bright white light in the early morning improves performance and advances sleep and circadian phase during the Antarctic winter

Previous work has demonstrated that exposure to an hour of bright light in the morning and the evening during the Polar winter has beneficial effects on circadian phase. This study investigated the effect of a single hour of bright white morning light on circadian phase, sleep, alertness and cognitive performance. Nine individuals (eight male, one female, median age 30years), wintering at Halley Research Station (75°S), Antarctica from 7th May until 6th August 2007, were exposed to bright white light for a fortnight from 08:30 to 09:30h, with two fortnight control periods on either side. This sequence was performed twice, before and following Midwinter. Light exposure, sleep and alertness were assessed daily by actigraphy, sleep diaries and subjective visual analogue scales. Circadian phase (assessed by urinary 6-sulphatoxymelatonin rhythm) and cognitive performance were evaluated at the end of each fortnight. During light exposure circadian phase was advanced from 4.97±0.96 decimal hours (dh) (mean±SD) to 4.08±0.68dh (p=0.003). Wake-up time was shifted by a similar margin from 8.45±1.83dh to 7.59±0.78dh (p<0.001). Sleep start time was also advanced (p=0.047) but by a lesser amount, consequently, actual sleep time was slightly reduced. There was no change in objective or subjective measures of sleep quality or subjective measures of alertness. An improvement in cognitive performance was found with both the Single Letter Cancellation Test (p<0.001) and the Digit Symbol Substitution Test (p=0.026) with preserved circadian variation. These beneficial effects of a single short duration light treatment may have implications not only for the Antarctic but other remote environments where access to natural light and delayed circadian phase, is problematic. These results require validation in larger studies at varying locations.     

Effect of shift work on the night-time secretory patterns of melatonin,prolactin, cortisol and testosterone

Summary In a study of the internal desynchronization of circadian rhythms in 12 shift workers, 4 of them, aged 25–34 years, agreed to be sampled every 2 h during their night shift (0000 hours to 0800 hours). They were oil refinery operators with a fast rotating shift system (every 3–4 days). We found marked changes in the secretory profiles of melatonin, prolactin and testosterone. Melatonin had higher peak-values resulting in a four-times higher amplitude than in controls. With respect to prolactin and testosterone, peak and trough times were erratic and the serum concentrations were significantly decreased in shift workers. Serum cortisol presented a decreased rhythm amplitude together with higher concentrations at 0000 hours in shift workers. This study clearly shows that fast rotating shift-work modifies peak or trough values and rhythm amplitudes of melatonin, prolactin, testosterone and cortisol without any apparent phase shift of these hormones. Whether the large rhythm amplitude of melatonin may be considered as a marker of tolerance to shift work, as reported for body temperature and hand grip strength, since it would help the subjects to maintain their internal synchronization, needs further investigation.     

Entrainment of the circadian activity rhythm of a lizard to melatonin injections

The circadian activity rhythms of lizards (Sceloporus occidentalis) can be entrained (synchronized) to a period of 24 hr by melatonin injections given every other day at the same time of day, but not by saline injections. The activity onsets of the entrained lizards exhibited two preferred phase-relationships (approximately 165 degrees and approximately 30 degrees) with the time of melatonin injections with the 30 degree phase only rarely observed. These results suggest that endogenous rhythms of melatonin secretion (i.e., from the pineal organ) may be involved in synchronizing circadian oscillations within the lizard's multioscillator circadian system.     

Exposure to light at night and risk of depression in the elderly

Background

Recent advances in understanding the fundamental links between chronobiology and depressive disorders have enabled exploring novel risk factors for depression in the field of biological rhythms. Increased exposure to light at night (LAN) is common in modern life, and LAN exposure is associated with circadian misalignment. However, whether LAN exposure in home settings is associated with depression remains unclear.

Methods

We measured the intensities of nighttime bedroom light and ambulatory daytime light along with overnight urinary melatonin excretion (UME) in 516 elderly individuals (mean age, 72.8). Depressive symptoms were assessed using the Geriatric Depression Scale.

Results

The median nighttime light intensity was 0.8 lx (interquartile range, 0.2–3.3). The depressed group (n=101) revealed significantly higher prevalence of LAN exposure (average intensity, ≥5 lx) compared with that of the nondepressed group (n=415) using a multivariate logistic regression model adjusted for daytime light exposure, insomnia, hypertension, sleep duration, and physical activity [adjusted odds ratio (OR): 1.89; 95% confidence interval (CI), 1.10–3.25; P=0.02]. Consistently, another parameter of LAN exposure (duration of intensity ≥10 lx, ≥30 min) was significantly more prevalent in the depressed than in the nondepressed group (adjusted OR: 1.71; 95% CI, 1.01–2.89; P=0.046). In contrast, UME was not significantly associated with depressive symptoms.

Limitation

Cross-sectional analysis.

Conclusion

These results suggested that LAN exposure in home settings is significantly associated with depressive symptoms in the general elderly population. The risk of depression may be reduced by keeping nighttime bedroom dark.     

Retinal mechanisms determine the subadditive response to polychromatic light by the human circadian system

Light is the major synchronizer of circadian rhythms to the 24-h solar day. The intrinsically photosensitive retinal ganglion cells (ipRGCs) play a central role in circadian regulation but cones also provide, albeit indirectly, input to these cells. In humans, spectrally opponent blue versus yellow (b-y) bipolar cells lying distal to the ganglion cell layer were hypothesized to provide direct input to the ipRGCs and therefore, the circadian system should exhibit subadditivity to some types of polychromatic light. Ten subjects participated in a within-subjects 3-night protocol. Three experimental conditions were employed that provided the same total irradiance at both eyes: (1) one unit of blue light (lambda(max)=450 nm, 0.077 W/m(2)) to the left eye plus one unit of green light (lambda(max)=525 nm, 0.211 W/m(2)) to the right eye, (2) one unit of blue light to the right eye plus one unit of green light to the left eye, and (3) 1/2 unit of blue light plus 1/2 unit of green light to both eyes. The first two conditions did not differ significantly in melatonin suppression while the third condition had significantly less melatonin suppression than conditions 1 and 2. Furthermore, the magnitudes of suppression were well predicted by a previously published model of circadian phototransduction incorporating spectral opponency. As was previously demonstrated, these results show that the human circadian system exhibits a subadditive response to certain polychromatic light spectra. This study demonstrates for the first time that subadditivity is due to spectrally opponent (color) retinal neurons.     

Modification of internal temperature regulation for cutaneous vasodilation and sweating by bright light exposure at night

Bright light (BL) exposure at night leads to suppressed secretion of melatonin and an attenuated fall in internal temperature at rest from the night to the early morning. However, it is unknown at the present whether typical diurnal variations in reflex responses to thermal challenges are similarly affected by BL exposure at night. We investigated the control of cutaneous vasodilator and sweating responses to hyperthermia in the early morning after artificial BL exposure at night, compare with dim light (DL) exposure. Six subjects stayed awake in a semi-supine position under DL (120 lx) or BL (2800 lx) conditions between 21.00 and 04.30 h. Urine samples were collected at 04.30 h. Beginning at 05.30 h, the lower legs were immersed for 50 min in 42°C water. The subjects remained awake for 21 h until the end of hot water immersion. Urinary 6-sulphatoxymelatonin levels following BL were significantly lower than after DL. Oesophageal temperature (T_es) before heating was significantly higher following BL [36.41±0.10 (DL) vs. 36.55±0.09 (BL)°C]. The T_es thresholds for the onset of cutaneous vasodilation and sweating were significantly higher with BL than with DL conditions (approximately 0.15°C, respectively). We found that the internal temperature threshold for thermoregulatory control of cutaneous vasodilation and sweating responses to passive heating in the early morning can be modified by the level of light exposure the prior night. Thus both basal internal temperature and the regulation of internal temperature are modified by BL exposure at night.     

Bright light treatment used for adaptation to night work and re-adaptation back to day life. A field study at an oil platform in the North Sea

Night workers complain of sleepiness, reduced performance and disturbed sleep due to lack of adjustment of the circadian rhythm. In simulated night-work experiments scheduled exposure to bright light has been shown to reduce these complaints. Here we studied the effects of bright light treatment on the adaptation to 14 days of consecutive night work at an oil platform in the North Sea, and the subsequent readaptation to day life at home, using the Karolinska sleep/wake diary. Bright light treatment of 30 min per exposure was applied during the first 4 nights of the night-shift period and the first 4 days at home following the shift period. The bright light exposure was scheduled individually to phase delay the circadian rhythm. Bright light treatment modestly facilitated the subjective adaptation to night work, but the positive effect of bright light was especially pronounced during the re-adaptation back to day life following the return home. Sleepiness was reduced and the quality of day was rated better after exposure to bright light. The modest effect of bright light at the platform was, possibly, related to the finding that the workers seemed to adapt to night work within a few days even without bright light. These results suggest that short-term bright light treatment may help the adaptation to an extended night-work period, and especially the subsequent re-adaptation to day life.     

Responsiveness of the aging circadian clock to light

The present study assessed whether advances in sleep times and circadian phase in older adults might be due to decreased responsiveness of the aging circadian clock to light. Sixteen young (29.3 ± 5.6 years) and 14 older adults (67.1 ± 7.4 years) were exposed to 4 h of control dim (10 lux) or bright light (3500 lux) during the night. Phase shifts of the melatonin rhythm were assessed from the nights before and after the light exposure. Bright light delayed the melatonin midpoint in both young and older adults (p < 0.001). Phase delays for the older subjects were not significantly different from those of the young subjects for either the bright or dim light conditions. The magnitude of phase delays was correlated with both sleep offset and phase angle in the older, but not the younger subjects. The present results indicate that at light intensities commonly used in research as well as clinical practice older adults are able to phase delay to the same extent as younger subjects.     

Impact of age and retinal degeneration on the light input to circadian brain structures

Aging causes anatomical and functional changes in visual and circadian systems. In wild type mice rods, cones, and photosensitive retinal ganglion cells (pRGCs) decline with age. In rd/rd cl mice, the early loss of rods and cones is followed by protracted transneuronal loss of inner retinal neurons as well as the pRGCs. Here we use Fos induction to study the light input pathway to the suprachiasmatic nuclei (SCN), the intergeniculate leaflets (IGL) and ventral lateral geniculate nuclei (vLGN) of old (∼700 days) and young (∼150 days) wild type and rd/rd cl mice. Cholera toxin tracing was used in parallel to study the anatomy of this pathway. We find that aging rather than retinal degeneration is a more important factor in reducing light input to the SCN, causing both a reduction in Fos expression and retinal afferents. Furthermore, we show light-induced Fos within the vLGN and IGL is predominantly subserved by rods and cones, and once again aging reduces the amplitude of this response.     

Fluid intake of rats in constant light and during feeding restricted to the light or dark portion of the illumination cycle

Rats restricted to eating and drinking during the light phase of a 12:12 light-dark (L-D) cycle (L-drinkers) consumed much smaller volumes of saccharin and NaCl than did rats whose feeding and drinking was restricted to the dark phase (D-drinkers). The patterns of fluid intake within the respective 12-hr feeding periods were markedly different for L- and D-drinkers and the food/fluid ratios were significantly lower for D- than for L-drinkers. It was concluded that illumination affects fluid intake independently of changes in food intake and that light limits the rat's capacity for fluid ingestion. L- and D-drinkers did not differ in their preference for saccharin over water in two bottle preference tests; this suggests that light does not interfere with the rat's ability to detect and determine the quality of the taste stimulus. Differences in ingestive behavior between L- and D-drinkers may in part reflect constraints imposed by changes in the sleep-wakefulness cycle. Intake of a wide concentration range of saccharin solutions was decreased in ad lib fed rats housed in constant light (L-L); differences in fluid intake between the L-L and L-D groups varied directly with the hedonic value of the saccharin solutions. Only 44% of rats housed in constant light as compared to 100% of rats maintained in a L-D cycle decreased their intake of a saccharin solution whose ingestion was followed by injection of lithium chloride. This finding is relevant to studies of illness-induced aversions and was related to circadian rhythms in drug susceptibility and their alteration in constant light. The necessity for controlling and specifying environmental illumination in studies of ingestive behavior was emphasized and various methodological considerations related to illumination cycles were discussed.     

Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report

The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses "exogenous" circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the "endogenous" circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from "Option" to "Guideline," depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs (Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline).     

Entrainment of the circadian activity rhythm to the light cycle: Effective light intensity for a Zeitgeber in the retinal degenerate C3H mouse and the normal C57BL mouse

Effective light intensities for entrainment of activity rhythms were obtained in the retinal degenerated C3Hf/He mice and the normal C57BL/6J mice. The circadian activity rhythms of the mice were examined under LD 12:12 cycles with one of five different levels of light (L phase) and complete darkness (D phase). The thresholds of a Zeitgeber, defined as the light intensity effective for 50% entrainment, were estimated between 1 lux and 5 lux in the C3H and lower than 0.01 lux in the C57BL mice. These results suggest that at least two different kinds of photoreceptor including rods and cones participate in the photic entrainment of the circadian activity rhythms.     

Effects of long working hours and the night shift on severe sleepiness among workers with 12‐hour shift systems for 5 to 7 consecutive days in the automobile factories of Korea

We investigated the effects of 12‐hour shift work for five to seven consecutive days and overtime on the prevalence of severe sleepiness in the automobile industry in Korea. [Correction added after online publication 28 Nov: Opening sentence of the summary has been rephrased for better clarity.] A total of 288 randomly selected male workers from two automobile factories were selected and investigated using questionnaires and sleep‐wake diaries in South Korea. The prevalence of severe sleepiness at work [i.e. Karolinska Sleepiness Scale (KSS) score of 7 or higher] was modeled using marginal logistic regression and included theoretical risk factors related to working hours and potential confounding factors related to socio‐economic status, work demands, and health behaviors. Factors related to working hours increased the risk for severe sleepiness at the end of the shift in the following order: the night shift [odds ratio (OR): 4.7; 95% confidence interval (CI): 3.6–6.0)], daily overtime (OR: 2.2; 95% CI: 1.7–2.9), weekly overtime (OR: 1.6; 95% CI: 1.0–2.6), and night overtime (OR: 1.6; 95% CI: 0.8–3.0). Long working hours and shift work had a significant interactive effect for severe sleepiness at work. Night shift workers who worked for 12 h or more a day were exposed to a risk of severe sleepiness that was 7.5 times greater than day shift workers who worked less than 11 h. Night shifts and long working hours were the main risk factors for severe sleepiness among automobile factory workers in Korea. Night shifts and long working hours have a high degree of interactive effects resulting in severe sleepiness at work, which highlight the need for immediate measures to address these characteristics among South Korean labor force patterns.     

Rapid and sensitive procedure for assigning idiotypic determinants to heavy or light chains: Application to idiotopes associated with the major cross-reactive idiotype of A/J anti-phenylarsonate antibodies

A rapid and sensitive procedure is described for assigning idiotypic determinants to heavy or light polypeptide chains. Heavy and light chains are resolved by electrophoresis in the presence of sodium dodecyl sulfate. The electrophoretically resolved polypeptides are then transferred to nitrocellulose filters. Filters containing bound heavy and light chains are incubated with ¹²⁵I-labelled anti-idiotypic antibody, and idiotype-anti-idiotype reactivity visualized by autoradiography. This procedure is illustrated with three monoclonal anti-idiotopic antibodies which recognize determinants associated with the major cross-reactive idiotype family of A/J anti-phenylarsonate antibodies. All three anti-idiotopic antibodies are shown to react with electrophoretically resolved idiotype heavy chain, but not with idiotype light chain.