Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance

Circadian phase resetting is sensitive to visual short wavelengths (450–480?nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480?nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age?±?SD: 31.3?±?4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2?h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p?<?0.01) and sleep efficiency (p?=?0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p?=?0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40?min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p?<?0.05) and middle (p?<?0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p?<?0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca)     

The CLOCK Gene and Mood Disorders: A Case-Control Study and Meta-analysis

The clock gene (CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study. As for function, rs1801260 has been speculated to affect mRNA. Therefore, the authors investigated the association between the three tagging single-nucleotide polymorphisms (SNPs) (rs3736544, rs1801260, and rs3749474) in CLOCK and risk of BP (n?=?867) and MDD (n?=?139) compared to controls (n?=?889) in the Japanese population. In addition, we also performed an updated meta-analysis of nine published, genetic association studies investigating the relationship between rs1801260 and mood disorder risk, comprising 3321 mood disorders cases and 3574 controls. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global p_BP?=?.605 and global p_MDD?=?.211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders. (Author correspondence: tarok@fujita-hu.ac.jp)     

The Pragmatic Approach to Masking

This paper advocates the use of a pragmatic approach to the problem of masking in real-life situations involving an abrupt change in the timing of sleep, i.e. shiftwork and “jet-lag” situations. Although “pure” chronobiological research has pointed to the importance of taking masking effects into account, the techniques that it has provided for doing so are extremely difficult to apply in real-life situations. The approach advocated here is based on Wever's pioneering work, and involves estimating the normative endogenous and exogenous components of the circadian rhythm in body temperature. These estimates are then used to: (a) simulate the results of shiftwork studies; and (b) to “remove” the exogenous component in “jet-lag” studies to allow analysis of the estimated endogenous component. The simulated curves obtained cross-correlated extremely highly with published night-shift temperature curves, while the “removal” of the exogenous component resulted in very similar findings to those obtained in temporal isolation studies. It is concluded that this pragmatic approach to masking may prove extremely useful in interpreting the results of field studies of shiftwork and “jet-lag”.     

Nocturnal Headache-Hypertension Syndrome: A Chronobiologic Disorder

The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term “nocturnal headache-hypertension syndrome” is proposed.     

Nocturnal Headache-Hypertension Syndrome: A Chronobiologic Disorder

The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term “nocturnal headache-hypertension syndrome” is proposed.     

Effects of Depressed Affect on Diurnal and Ultradian Variations in Mood in a Healthy Sample

The study investigated diurnal and ultradian variations in cheerful and depressed mood in a healthy sample, and examined whether these variations were related to severity of depressed affect. Thirty employed volunteers used a pocket computer to complete self-rating scales of depression and cheerfulness every 2 h for 14 days except during sleep periods. They also completed the Beck Depression Inventory (BDI) and the General Health Questionnaire (GHQ). Analysis of variance of depressed mood showed a significant interaction between time of day and BDI/GHQ, in which only the mood of the high BDI/GHQ groups got worse during the day. The low BDI group showed a diurnal variation in cheerful mood in which mood was at its best in the early evening. Cosinor and “binfit” analysis of raw and residual time-series showed that more than half of the participants had significant fitting ultradian rhythms in mood in the range 3-9 h. However, only the number of significant fits for residual cheerful mood was substantially above the level of chance. The amplitudes of the ultradian rhythms in raw depressed mood were greater in participants scoring higher on the BDI/GHQ scales, but this seemed to reflect an increase in serial dependency between depressed mood states. The results are discussed in relation to circadian rhythms in mood and depression.     

A Preliminary Investigation into Individual Differences in the Orcadian Variation of Meal Tolerance: Effects on Mood and Hunger

A forced desynchrony methodology was used to assess postprandial blood glucose in 9 female volunteers during a 3-h period following a mixed meal presented at four times of day (08:00, 14:00, 20:00, 02:00). The influence of time of day on the postmeal glucose responses was evaluated by calculating the area under the curve, largest increase, time taken to reach peak, and fasting level. Circadian variations in meal tolerance were found for the area under the curve and largest increase, responses were greater (indicating poorer meal tolerance) in the evening than the morning. Fasting blood glucose exhibited diurnal variation although in the opposite direction to meal tolerance; levels were higher in the morning than the evening. Time taken to reach peak levels was not modulated by circadian rhythmicity. Estimates of the timing of poorest meal tolerance and the magnitude of this intolerance were computed for each subject. Individual differences in the magnitude of meal intolerance were found to influence hunger and self-reported calmness. Subjects with good tolerance had rhythms in both calmness and hunger, which were not found in those with poor tolerance. Subjects with good tolerance also tended to rate themselves as feeling more calm. These mood and hunger effects may result from differences in insulin resistance, which is hypothesized to underlie the circadian variations in meal tolerance. (Chronobiology International, 13(6), 435-447, 1996)     

Varying the Length of Dim Nocturnal Illumination Differentially Affects the Pacemaker Controlling the Locomotor Activity Rhythm of Drosophila Jambulina

Photic entrainment of animals in the field is basically attributed to their exposure to the dimly lit nights flanked by the dawn and dusk twilight transitions. This implicates the functional significance of the dimly lit nights as that of the twilight transitions. Recently, the authors have demonstrated that the dimly lit night at 0.0006 lux altered the attributes of the circadian rhythm of locomotor activity of Drosophila jambulina. The present study examined whether the durations of such dimly lit nights affect the entrainment and free-running rhythmicity of D. jambulina. Flies were subjected for 10 days to two types of 24-h lighting regimes in which the photophase (L) was at 10 lux for all flies but the scotophase, which varied in duration from 9 to 15?h, was either at 0 lux (D phase) for control flies or 0.0006 lux (the artificial starlight or S phase) for experimental flies. Thereafter, they were transferred to constant darkness (DD) to compare the after-effects of the dimly lit nights on the period (τ) of free-running rhythm in DD with that of the completely dark nights. Control flies were entrained by all LD cycles, but the experimental flies were entrained only by five LS cycles in which the duration of the S phases ranged from 10 to 14?h. The two LS cycles with very short (9?h) and long (15?h) S phases rendered the flies completely arrhythmic. Control flies started activity shortly before lights-on and continued well after lights-off. The experimental flies, however, commenced activity several hours prior to lights-on but ended activity abruptly at lights-off as the result of a negative masking effect of nocturnal illumination. Length of the midday rest was considerably shorter in the control than in the experimental flies in each lighting regime. The active phase in the control flies was predictably shortened; nonetheless, it was invariable in the experimental flies as the nights lengthened. Transfer from lighting regimes to DD initiated robust free-running rhythmicity in all flies including the arrhythmic ones subjected to LS cycles with 9 and 15?h of scotophases. The τ was profoundly affected by the nocturnal irradiance of the prior entraining lighting regime, as it was always shorter in the experimental than in the control flies. Thus, these results indisputably demonstrate the changes in fundamental properties of the circadian pacemaker of D. jambulina were solely attributed to the extremely dim nocturnal irradiance. This strain of D. jambulina is entrained essentially by the dimly lit natural nights, since it is never exposed to the prevailing photic cues such as the twilight transitions or bright photoperiod, owing to the dense vegetation of its habitat. (Author correspondence: drdsjoshi08@gmail.com)     

Circadian Rhythms in 6-Sulphatoxymelatonin and Nocturnal Sleep in Blind Children

This article describes the relationship between melatonin secretion and sleep quality and subjective complaints about sleep in totally blind children. Eleven boarding-school children (mean age 15.2 years) participated. The major urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) was measured five times a day for 48 h. Sleep-wake cycles were recorded by continuous actigraphic recordings during the same time period. Results showed that delayed secretory peaks in aMT6s were significantly associated with disturbed nocturnal sleep and with complaints about morning fatigue.     

Circadian Rhythms in 6-Sulphatoxymelatonin and Nocturnal Sleep in Blind Children

This article describes the relationship between melatonin secretion and sleep quality and subjective complaints about sleep in totally blind children. Eleven boarding-school children (mean age 15.2 years) participated. The major urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) was measured five times a day for 48 h. Sleep-wake cycles were recorded by continuous actigraphic recordings during the same time period. Results showed that delayed secretory peaks in aMT6s were significantly associated with disturbed nocturnal sleep and with complaints about morning fatigue.     

Evening types demonstrate reduced SSRI treatment efficacy

Selective serotonin reuptake inhibitors (SSRIs) have a profound effect on the circadian system's response to environmental light, which may impact treatment outcomes for patients depending on their habitual light exposure patterns. Here, we investigated the relationship between time-of-day preference, depressive symptoms and self-reported antidepressant treatment response. Evening types reported having taken a higher number of antidepressant medications in the previous 5 years and lower SSRI efficacy than morning types. While undergoing SSRI treatment, evening types also reported more depressive symptoms and suicidality. It is concluded that time-of-day preference may prove informative in predicting SSRI treatment responses.     

The Difference Between Activity When in Bed and out of Bed. III. Nurses on Night Work

Eight nurses have been studied during rest days and three successive night shifts. Measurements of wrist activity have been made and used to assess the extent to which the pattern of daily activity changes between control (rest) days and days involving night work. One analysis considered wrist activity during time spent in bed; this appears to decrease in parallel with the amount of time in bed that is lost during night work but, when this effect is corrected for, there is greater activity during time spent in bed in the daytime compared with control days (when time in bed is during the night). The dichotomy of activity (between lower values during time spent in bed and higher values when out of bed) also decreases if time in bed is during the daytime while on night shifts. These changes in the amount of wrist activity and the dichotomy between activity in and out of bed are related to the changed quality and quantity of sleep that has been measured by self-report questionnaires and the sleep EEG. It is concluded that results from wrist actimetry can provide valuable information regarding the process of adjustment to night work, and that its convenience (to subject and experimenter), coupled with the new analytical approaches described here, make it a viable method for field studies. (Chronobiology International, 13(4), 273-282, 1996)     

大学生亚健康状态和心境状态的对比及相关性研究

目的:用亚健康自评量表和心境量表检测大学生的心身状态以及两种测量方法的对比和关联.方法:被试为120名大学生,全部来自大连理工大学,进入实验室后先休息约5分钟并填写被试信息表,然后进行心境量表POMS(profile of mood states)量表测试和亚健康自评量表SRSHS(self-rating sub-health scale)测试,POMS量表取TMD总分作为心境指标,亚健康量表取总分作为亚健康状态指标,用SPSS软件对数据做统计分析.结果:两种量表得分男生都显著高于女生,两种指标极显著正相关,心境量表TMD总分在110-160间的被试人数比率和亚健康被试人数比率相当.结论:大学生群体中,亚健康者占有约2/3的比率,女生的心身状态要好于男生;负性心境是亚健康状态的一个主要原因;心境TMD总分在110-160间的被试处于不同程度的亚健康状态.     

Effect of Light Intensity on the Phase and Period Response Curves in the Nocturnal Field Mouse Mus booduga

The effect of light intensity on the phase response curve (PRC) and the period response curve (τRC) of the nocturnal field mouse Mus booduga was studied. PRCs and τRCs were constructed by exposing animals free-running in constant darkness (DD), to fluorescent light pulses (LPs) of 100 lux and 1000 lux intensities for 15min duration. The waveform of the PRCs and τRCs evoked by high light intensity (1000 lux) stimuli was significantly different compared to those constructed using low light intensity (100 lux). Moreover, a weak but significant correlation was observed between phase shifts and period changes when light stimuli of 1000 lux intensity were used; however, the phase shifts and period changes in the 100 lux PRC and τRC were not correlated. This suggests that the intensity of light stimuli affects both phase and period responses in the locomotor activity rhythm of the nocturnal field mouse M. booduga. These results indicate that complex mechanisms are involved in entrainment of circadian clocks, even in nocturnal rodents, in which PRC, τRC, and dose responses play a significant role.     

Once-Daily Evening Administration of Uniphyl Tablets: Announcement of First Available Chronotherapy of Nocturnal Asthma

Theophylline chronotherapy recently became a reality for patients with reversible airways disease. Uniphyl^R 400 mg tablets (controlled-release theophylline, the Purdue Frederick Company, Norwalk, Connecticut) are now indicated for once-daily evening administration, both in the United States and Canada. This development follows the previous use of Uniphyl tablets in once-daily morning doses and marks the first-available antiasthmatic treatment in North America to incorporate dosing time as an important therapeutic dimension. It reflects increasing recognition, by the medical community, of the need to consider the individual patient's timing of symptoms in relation to the kinetics of the drug.     

Neuropsychological Outcomes of Nocturnal Asthma

In spite of frequent reports that nocturnal asthma results in fatigue and impaired cognitive performance, there exists little objective evidence as to the daytime consequences of this disorder. Treatment studies have established that the symptoms of nocturnal asthma improve with medication intervention, but performance does not. Studies of obstructive sleep apnea (OSA), a source of generally more severe sleep fragmentation, have demonstrated that measurement of sleep-deprivation effects is limited to tasks requiring heightened alertness and rapid information processing, and that the degree of score change is related to the degree of sleep disruption. Studies of normal, but sleep-deprived, subjects indicate that (1) utilization of repetitive measures sustained for long duration can potentiate motivation to overcome the effects of fatigue in the laboratory, and (2) even when average scores do not change significantly, performance becomes more irregular. These collective findings about the measurement of performance impairment secondary to sleep deprivation can be used to guide new studies of nocturnal asthma. Finally, children must be included in future investigations because they may be at even greater risk for daytime consequences of nocturnal asthma than adults.     

24-Hour Pattern of Work-Related Injury Risk of French Firemen: Nocturnal Peak Time

The first aim of the study was to assess clock-time patterning of work-related injuries (WRIs) of firemen (FM) of Saône et Loire-71 (France) during the 4-yr span of 1 January 2004 to 31 December 2007. FM of this service are legally required to log every WRI and seek its evaluation by the medical service, whether the WRI was the result of worksite duties or exercise/sport activities at the station. WRI was defined specifically as a (nonexercise, nonsport, and nonemotional/stress) work-associated trauma, verified both by log book and medical records. For the corresponding years, the 24-h pattern of emergency calls (Calls) plus road traffic (Traffic) on the main roads of the service area was also assessed. Relative risk (R) of WRI was calculated as the quantity of WRIs/h divided by the quantity of Call responses/h?×?1000, which takes into account the number of at-risk FM/unit time, since each dispatched emergency vehicle is staffed with 4 FM. Comparably trained regular (RFM) and volunteer (VFM) FM experienced a total of 187 WRIs. The 24-h WRI curve patterns of RFM and VFM were correlated (r?=?0.4, p?<?.05), with no histogram difference (p?>?.05). Analysis of variance (ANOVA) validated comparable clock-time patterns in WRIs of RFM and VFM each year and each season (all p?<?.0001). Thus, time series of the RFM and VFM were pooled, revealing a statistical significant 24-h variation in WRIs (ANOVA, p?>?.0006; Cosinor analysis, p?<?.0001), with peak at 16:00?h and trough at 04:00?h. The 24-h pattern in Traffic, which mirrors that of human activity, with peak ～18:00?h and trough ～03:00?h, was also verified (ANOVA, p <?.0001; Cosinor, p?<?.0001). Calls (n?=?112,059) resulting in FM responses also exhibited statistically significant 24-h variation, with peak at ～20:00?h and trough at ～06:00?h. The 24-h pattern of R showed a nocturnal peak at 02:00?h (R?=?2.87?±?0.46; mean?±?SEM) and diurnal trough 14:00?h (R?=?1.30?±?0.05) (t test, p?<?.02); clock-time-related changes in R were further validated by ANOVA (p?=?.0001) and Cosinor (p?<?.0001), with acrophase (peak time, Ø) of 02:43?h?±?68?min (SD). The second aim of the study was to evaluate the relationship between the 24-h patterns of WRIs and lag-time (LT) response (used as a measure of work performance) of FM of the same service to urgent medical calls for out-of-hospital cardiac arrests. Highest R of WRI at 02:00?h corresponded closely to longest LT (raw data at ～02:00?h and Cosinor derived Ø of 02.54?h?±?71?min [SD]), thereby supporting the hypothesis of a common mechanism underlying the two 24-h profiles. A third aim was to determine the relevance of a new concept in work safety, “chronoprevention,” for future FM training programs. (Author correspondence: bergarein@yahoo.fr)     

Neuropsychological Outcomes of Nocturnal Asthma

In spite of frequent reports that nocturnal asthma results in fatigue and impaired cognitive performance, there exists little objective evidence as to the daytime consequences of this disorder. Treatment studies have established that the symptoms of nocturnal asthma improve with medication intervention, but performance does not. Studies of obstructive sleep apnea (OSA), a source of generally more severe sleep fragmentation, have demonstrated that measurement of sleep-deprivation effects is limited to tasks requiring heightened alertness and rapid information processing, and that the degree of score change is related to the degree of sleep disruption. Studies of normal, but sleep-deprived, subjects indicate that (1) utilization of repetitive measures sustained for long duration can potentiate motivation to overcome the effects of fatigue in the laboratory, and (2) even when average scores do not change significantly, performance becomes more irregular. These collective findings about the measurement of performance impairment secondary to sleep deprivation can be used to guide new studies of nocturnal asthma. Finally, children must be included in future investigations because they may be at even greater risk for daytime consequences of nocturnal asthma than adults.     

Physical Fitness and Other Individual Factors Relating to the Shiftwork Tolerance of Women

Maximal oxygen consumption (V˙O₂max), muscle strength (MS) and physical activity were compared to age, shiftwork experience, morningness, personality traits and social factors intervening in the shiftwork tolerance of 128 women. The subjects were nurses and nursing aids working irregular shifts in a hospital. Neuroticism was the most powerful negative factor connected to higher fatigue and various symptoms of the subjects. High V˙O₂max and good MS were, on the other hand, the most important positive factors connected to lower fatigue and musculoskeletal symptoms and better sleep quality of the subjects. In different shifts, fatigue, sleep length and quality were influenced most by morningness. It is concluded that physical fitness is an important individual factor explaining the variations of shiftwork tolerance in women.     

The effects of a split sleep–wake schedule on neurobehavioural performance and predictions of performance under conditions of forced desynchrony

Extended wakefulness, sleep loss, and circadian misalignment are factors associated with an increased accident risk in shiftwork. Splitting shifts into multiple shorter periods per day may mitigate these risks by alleviating prior wake. However, the effect of splitting the sleep–wake schedule on the homeostatic and circadian contributions to neurobehavioural performance and subjective assessments of one’s ability to perform are not known. Twenty-nine male participants lived in a time isolation laboratory for 13?d, assigned to one of two 28-h forced desynchrony (FD) schedules. Depending on the assigned schedule, participants were provided the same total time in bed (TIB) each FD cycle, either consolidated into a single period (9.33?h TIB) or split into two equal halves (2?×?4.67?h TIB). Neurobehavioural performance was regularly assessed with a psychomotor vigilance task (PVT) and subjectively-assessed ability was measured with a prediction of performance on a visual analogue scale. Polysomnography was used to assess sleep, and core body temperature was recorded to assess circadian phase. On average, participants obtained the same amount of sleep in both schedules, but those in the split schedule obtained more slow wave sleep (SWS) on FD days. Mixed-effects ANOVAs indicated no overall difference between the standard and split schedules in neurobehavioural performance or predictions of performance. Main effects of circadian phase and prior wake were present for both schedules, such that performance and subjective ratings of ability were best around the circadian acrophase, worst around the nadir, and declined with increasing prior wake. There was a schedule by circadian phase interaction for all neurobehavioural performance metrics such that performance was better in the split schedule than the standard schedule around the nadir. There was no such interaction for predictions of performance. Performance during the standard schedule was significantly better than the split schedule at 2?h of prior wake, but declined at a steeper rate such that the schedules converged by 4.5–7?h of prior wake. Overall, the results indicate that when the total opportunity for sleep per day is satisfactory, a split sleep–wake schedule is not detrimental to sleep or performance. Indeed, though not reflected in subjective assessments of performance capacity, splitting the schedule may be of some benefit, given its reduction of neurobehavioural impairment at night and its association with increased SWS. Therefore, for some industries that require operations to be sustained around the clock, implementing a split work–rest schedule may be of assistance.