Dissertation Night work - Altered sleep - wake Cycles and the Circadian Body Clock

1. NIGHT WORK: ALTERED SLEEP-WAKE CYCLES
AND THE CIRCADIAN BODY CLOCK
by
Wong Sook Yen
Dissertation Supervisor: Prof. Jim Waterhouse
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2. NIGHT WORK: ALTERED SLEEP-WAKE CYCLES AND THE
CIRCADIAN BODY CLOCK
Wong Sook Yen
BSc (Hons) Chemistry and Biology
Liverpool John Moores University
Person No.: 467226
ABSTRACT
Night work must be performed by all involved in the demands of our “24-h society”. For some,
problems arise: sleep disturbances, reductions in task performance at night, more health disorders and social
problems. There is a basic conflict between adopting a nocturnal lifestyle, the “body clock”, and environmental
time-cues such as the light-dark cycle.
This review focuses on the interactions between these factors in individuals living normally, and shows
that the system adapts poorly to changes required in night workers. Time-zone shifts have much in common
with night work, and the effects of both are compared. Inter-individuals differences are important, and a genetic
component determines an individual‟s tolerance to night work and sleep loss.
Advice to night workers covers; naps to improve performance and maximize alertness during work;
improving daytime sleep; using leisure time better; and altering meal schedules. Adjusting to night work by
light exposure and dealing with rest days are explained.
Better understanding is required on mechanisms underlying the sleep-wake cycle and mental
performance, and the role of genes in inter-individual differences. Night work is abnormal biologically and
managers, family and friends should understand the difficulties faced by all night workers.
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3. ACKNOWLEDGEMENT
I would like to take this pleasant opportunity to express my profound sense of gratitude, respect and
sincere thanks to my ever inspiring supervisor Prof. Jim Waterhouse for his valuable guidance, constant
encouragement, critical evaluation, prompt help and advice during the entire period of work.
I am thankful to Dr Simon Dowell, for his unstinted help and valuable guidance during the course of
this dissertation.
I express my heartfelt gratitude to my parents and family members for their understanding and
immense support during my study.
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4. 1. Night Work
Following technological advances, particularly the invention of artificial lighting, the opportunity has arisen for
the sleep-wake cycle to be altered from one that is synchronized with the solar day. Today, about 1 in 5 workers
in Europe is employed on shift work involving night work (Harrington, 2001). Disruption of the circadian
system during night work may lead to deterioration in many aspects of a person‟s general well-being and, in the
longer term, various negative health consequences.
This review summarizes the latest evidence and reasons for such negative effects, including the interaction
between chronobiology and genetics in those doing night work. Possible methods of promoting their well-being
will also be considered.
1.1. The Need for Night Work
Night work is demanded by the need for round-the-clock operation – due to economic need to offset plant
obsolescence and improve plant productivity, and to technical requirements of some industrial processes. Also,
emergency and essential services (medical, fire and law enforcement) must be provided throughout the 24 h, and
shops, newspapers and hotels provide a 24-h service. In all cases, the employees must work at night; working
“9-to-5” is by no means universal.
1.2. Problems Associated with Night Work
Night work is associated with several negative effects, both in the short and long terms.
1.2.1. Short-terms Problems Associated with Night Work
Daily schedules of sleep and wakefulness, social activities and meals are all altered. Such disruptions often
result reduced quantity and quality of sleep, and social isolation; physiological effects include changes in core
temperature, hormone levels and immune function (Berger and Hobbs, 2006). Evidence of poorer work
performance and increased accidents have been reported (Harrington, 1994). Recent major disasters attributed to
human error (Exxon Valdez oil spill, Three Mile Island nuclear power plant emergency, for example) occurred
on the night shift, when alertness is lowest (ACEP, 2003).
The minimum amount of sleep a person needs to maintain high performance levels is about 4.5-5.5 h (Naitoh et
al., 1993). A 5-h period of sleep is easily obtained by day workers (sleeping at night) but not by night workers
(sleeping in the daytime); this shorter sleep is not only due to light and noise but also to physiological factors.
Whatever the cause, excessive sleepiness when awake is often encountered by night workers.
Sleep disturbances can be measured in the field without disrupting daily activities by an actimeter, a small
device worn on subjects‟ non-dominant wrist. Figure 1 shows the activity measured in subjects living normally
(nocturnal sleep) and night workers sleeping during the daytime; nocturnal sleep (top) is associated with less
activity (uninterrupted sleep) than daytime sleep (bottom), where short awakenings are evident.
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5. Figure 1. A: activity of a healthy individual living normally and sleeping at night. C: a night worker sleeping
during the daytime. Time in bed is shown by a horizontal bar. (Minors et al., 1996)
1.2.2. Long-term Problems Associated with Night Work
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6. Reduced ability to sleep in the daytime and general fatigue when awake lead to negative effects upon mood and
lifestyle. Figure 2 indicates the effects upon family and social activities, and negative effects of night work,
particularly if accompanied by insomnia, are clear. Social implications, such as increased frequencies of divorce,
substance abuse and depression, are also present, and the tendency to miss work is increased (Figure 3).
Figure 2. Mean number of days of missed family and social activities (+ SE) during past 3 months in day, night,
and rotating-shift workers with/without insomnia and/or excessive sleepiness (ES) (From Drake et al., 2004).
Figure 3. Mean number of days of missed work during past three months (+ SE) in day, night, and rotating shift
workers. Results grouped by presence/absence of insomnia and presence/absence of excessive waking
sleepiness (From Drake et al., 2004).
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7. One of the most disturbing reactions to night work is poorer health, believed to result from continually disturbed
physiologicaly, neurohormonal regulation and gene expression. Evidence for a link between shift work and
increased cardiovascular risk has strengthened in recent years (Bøggild and Knutsson, 1999; Harrington, 1994),
and increased occurrence of gastrointestinal disease (Figure 4) has also been linked to repeated alterations of
daily schedules required by night work.
Figure 4. Prevalence of peptide ulcers among day, night and rotating shift workers with/without insomnia
and/or excessive sleepiness (From Drake et al., 2004).
Reviews (IARC Monographs Programme) have reported that shift work increased the potential of tumor and
cancer development in humans. The studies by Schernhammer et al. (2001) on nurses working night shifts
indicated significantly increased risk of breast cancer compared with day workers, as found also by Megdal et al.
(2005), who studied female flight-attendants (who frequently cross time zones and so have continually changing
schedules). That is, frequent changes to the sleep-wake cycle, either from night work or time-zone transitions,
are associated with increased carcinogenesis (Chen et al., 2005).
These negative effects of night work are due not only to changes in lifestyle but also to living “against” the body
clock. In order to understand this problem, and so to be able to offer rational advice, evidence for the presence
of a body clock, its properties, and effects upon the body, need to be considered.
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8. 2. Biological Rhythms
In spite of the importance of homeostasis (maintaining biological variables within narrow limits) to health,
repeated measurements during the course of 24 h in subjects active in the daytime and asleep at night indicate
that variables show daily rhythms (see Figure 5). The majority (core temperature, for example) peak in the
daytime and show a nocturnal trough; by contrast, cortisol and other endocrine rhythms (growth hormone and
melatonin, for example) peak during the night. The body‟s physiology alternates between daytime activity and
nocturnal recuperation during sleep.
Figure 5. The normal daily variations in deep body (rectal) temperature, plasma 11-hydroxycorticosteroids
(cortisol), blood pressure and urinary excretion of potassium in a healthy subject (From Minors and Waterhouse,
1984).
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9. 2.1. Evidence for a Body Clock
Daily rhythms do not arise only because of an individual‟s rhythmic lifestyle and environment. This can be
demonstrated by requiring subjects to perform a “constant routine” protocol, which minimises rhythmicity in
lifestyle and environment. Subjects are required to remain awake and sedentary (not engaging in active pursuits)
in an environment of constant temperature and lighting for at least 24 h, and identical snacks are provided at
regular intervals. The rhythm of core temperature illustrates the result obtained (Figure 6).
Figure 6. Mean rectal temperature measured hourly in 8 subjects living a normal existence (full line) and in the
same subjects awoken at 04:00 h and spending the subsequent 24 h awake and undergoing a “constant routine”
protocol (broken line) (From Minors and Waterhouse, 1984).
In spite of no alternation between sleep and wakefulness during the constant routine, the rhythm of core
temperature persists, though with reduced amplitude. This remaining rhythm is endogenously generated,
therefore, and is attributed to the body clock. Since the two curves in Figure 6 are not identical, the individual‟s
lifestyle and environment also produce some effect, the exogenous component of the rhythm. These two
components are normally in phase (Waterhouse, 2002), the morning rise of core temperature produced by the
body clock being accentuated by waking up in a bright, noisy and dynamic environment and the evening fall
being accompanied by relaxing in a quieter, darker environment.
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10. 2.2. The Body Clock and Clock Genes
2.2.1. General Structure and Activity
The body clock is found in the suprachiasmatic nuclei, SCN, paired structures containing about 20,000 neurons
located in the hypothalamus just above the optic chiasma. The SCN directly receive sensory inputs from
photoreceptors in the retina via the retino-hypothalamic tract. The rhythmic output from the SCN travels to
regions of the brain which affect temperature regulation, the sleep-wake cycle, the autonomic nervous system
and the endocrine system – through which the whole body becomes rhythmic. An output also goes to the pineal
gland, which responds to light by switching off production of its hormone, melatonin (NINDS, 2007). The level
of melatonin normally increases after darkness, making people feel drowsy and preparing them to sleep. These
effects of the SCN are achieved at a molecular level by coordinating the rhythmic cycling of gene expression in
the body, a coordination achieved through neural and hormonal pathways (Phillips, 2009).
2.2.2. Clock Genes
Several genes cycle with a period of about 24 h both in the brain and the rest of the body (Philips, 2009); these
include period (Per), clock (clk), cycle (cyc), timeless (tim), frequency (frq) and doubletime (dbt) (Miyamoto
and Sancar, 1999). They are the master genes that are associated with rhythmic changes in the body, the protein
products of which are components of self-sustaining negative feedback loops, their concentration determining
biological time (Okamura et al., 2002). Figure 7 illustrates the interactions between the genes and their protein
products.
Figure 7. A schematic model of the genetic and molecular clockwork of the circadian clock in mammals.
Curved lines represent messenger RNAs and small circled P‟s, phosphates. For more details, see text
(Cermakian and Boivin, 2003).
A self-sustaining rhythmicity is achieved by this system: in the morning, the promoters of the Cry and Per genes
are activated by the CLOCK and BMAL1 proteins (rectangles C and D), producing mRNA transcripts that are
exported into the cytoplasm. These mRNAs are translated into proteins throughout the day and PER (1, 2 and 3)
and CRY (1 and 2) proteins accumulate in the cytoplasm. In the evening, the different CRY and PER molecules
combine, are phosphorylated by casein kinase (CK-I), and then enter the nucleus at night. These molecules
inhibit the expression of Per and Cry genes. As a result, CRY and PER mRNA and proteins degrade and
disappear towards the early morning, thereby releasing their inhibition on CLOCK and B-MAL1. The cycle then
repeats itself. Clock genes Per1 and Per2 are rapidly induced by light in the SCN, and are believed to mediate
photic resetting of the molecular clock by zeitgebers (below) (Shigeyoshi et al., 1997; Yan et al., 1999).
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11. 2.2.3. Controlling the Timing of the Body Clock
The SCN cannot be studied directly; instead, the rhythm of core temperature is used as a marker (see Figure 6).
If individuals are studied living for several days in a time-free environment (an underground cave, for example),
the rhythms that are measured are said to be “free-running”. All rhythms, including the sleep-wake cycle and
core temperature, continue but they show a period slightly greater than 24 h. These rhythms are termed
“circadian” (Latin: “about a day”), and this period is believed to be the natural period of the body clock. Recent
studies using very dim light during the wake time or blind subjects estimate that the period is about 24.3 h
(Czeisler et al., 1999).
Therefore, for the body clock to be a useful timing device, it must be adjusted to a period of 24 h, equal to the
solar day. This adjustment is achieved by rhythms in the individual‟s lifestyle and external environment called
“zeitgebers” (German: “time-giver”). The rhythms of activity, social interactions and food intake play some role,
but the light-dark cycle, coupled with rhythmic melatonin secretion (in phase with the light-dark cycle), is most
important.
When light acts upon the body clock, its effect depends on the time of presentation relative to the temperature
minimum (normally around 05:00 h, Figure 6). Light presented in the 6 h after this minimum advances the body
clock, in the 6 h before, delays it, and at other times exerts no effect (Khalsa et al., 2003). This relationship
between the time of light exposure and the phase shift of the body clock is called a Phase Response Curve, PRC
(Figure 8).
Figure 8. Phase response curve of human circadian rhythm. Dark bars indicate sleeps on successive days
(plotted downwards) (From Khalsa et al., 2003).
Melatonin also adjusts the phase of the body clock, its PRC mirroring that of light (Lewy et al., 1999; Shochat
et al., 1997); ingestion in the afternoon and early evening advances the body clock and, in the second half of
sleep and during the early morning, delays it. Since bright light inhibits melatonin secretion, the clock-shifting
effects these two zeitgebers reinforce each other; bright light in the hours immediately after the temperature
minimum advances the body clock not only directly (via the PRC to light) but also indirectly (by suppressing
melatonin secretion and so preventing the phase-delaying effect that melatonin would have exerted at this time).
All zeitgebers normally act harmoniously to synchronise the phase of the body clock with the solar day.
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12. 2.3. Rhythms Caused by the Body Clock
The body clock induces rhythmicity throughout the body, but rhythms of sleep and cognitive performance are
most relevant to night workers.
2.3.1. Sleep
2.3.1.1. Sleep Quantity
The quantity of sleep achieved depends upon the ease of getting to sleep and remaining asleep.
A. The ultra-short sleep-wake paradigm (Shochat et al., 1997) has been used to investigate the ease of getting to
sleep at different times of the day. This protocol divides a period of 24 h into 72 x 20-min segments. In each
segment, subjects attempt to sleep for 7 min; the amount of sleep obtained is monitored by EEG. For the next 13
min, subjects are required to be awake. This cycle is repeated throughout a 24-h period, so that the ease of
getting to sleep can be estimated. Results indicate that getting to sleep is easiest when core temperature is lowest
and hardest when it is highest.
B. If subjects are allowed to sleep and the chance that they will wake spontaneously in the next hour is
considered, the result shown in Figure 9 (right) is found. Waking becomes far more likely between 07:00-11:00
h (when core temperature is rising) and far less likely between 19:00-23:00 h (core temperature is falling).
Figure 9. Left: Number of minutes of sleep following different times of retiring. Right: Chance of a sleeping
subject waking up in the next hour (From Waterhouse et al., 2002).
C. Combining these results explains why spontaneous sleep length depends upon the time of day when the sleep
is taken (Figure 8, left). For night workers, for example, falling asleep early in the morning (after the night shift)
might be easy (low core temperature), but sleep length is curtailed by rising core temperature later in the
morning. By contrast, for day workers, going to sleep in the late evening (body temperature falling) is quite easy,
and waking will not occur until after the temperature trough. This enables a sleep sufficiently long for full
recuperation to be obtained.
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13. 2.3.1.2. Sleep Quality
The architecture of normal sleep is based on measures of brain activity, eye movements and chin muscle activity
and described according to the criteria established by Rechtschaffen and Kales (1968).
Sleep can be divided into two distinct types, rapid eye movement (REM) and non-REM (N-REM) sleep. A sleep
cycle begins with Stages 1 to 4 of N-REM sleep (reflecting increasing depths of sleep and increasingly
synchronized activity between the cortical brains cells) followed by REM sleep (Figure 10). There are
approximately 4–5 N-REM/REM cycles during a typical night's sleep. Stage 1 of N-REM sleep is the transition
between waking and sleep when awareness of the individual‟s surroundings is lost and the brain deactivates.
During N-REM sleep, the brain is in a resting phase, characterized by decreased autonomic function and
increased neuroendocrine secretions (Hobson, 1999). SWS (Stages 3 and 4) is considered to reflect the
recuperative role of sleep and predominates in the early part of sleep, its amount being proportional to prior
wakefulness (Taub and Berger, 1973). Successive cycles of nocturnal sleep contain less N-REM and more REM
sleep, and memory consolidation occurs during this stage (Robson, 2010). The amount of REM sleep is
proportional to how low is core temperature rather than to prior wake time.
Figure 10. Distribution of sleep stages across a typical night of human sleep. Horizontal axis: time elapsed from
23:30 h to 07:00h. Vertical axis: stages of REM and N-REM sleep. The shaded bars below the dotted line cover
the periods of N-REM sleep, showing Stages 1-4. Stages 3 and 4 are usually grouped together as slow wave
sleep (SWS). Shaded bars above the dotted line represents periods of REM sleep (From Peigneux et al., 2001).
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14. 2.3.2. Rhythms of Performance
Changes in self-rated subjective feelings and mental performance have been measured in waking subjects living
a conventional sleep-activity schedule (Folkard, 1990; Blatter and Cajochen, 2007). Rhythmic changes are
present, with worse performance in the early morning and late evening, and best performance in the middle of
the day. It is uncommon to measure performance during the night, such measurements requiring subjects to
remain awake or be woken. Nevertheless, when these measurements are made (Monk et al., 1997), values are
lower than during the daytime.
The detailed time-course of mental performance rhythms differs between “simple” and “complex” task
(requiring little or much cognitive activity, respectively), simple tasks showing closer parallelism with core
temperature (Figure 11).
Figure 11. Mean variation of mental performance and alertness during the daytime (Kleitman, 1933).
These differences can be considered to reflect variations in the rate at which decrements occur due to time
elapsed since waking. As the task‟s cognitive element increases, this deterioration increases, and this makes the
rhythm peak earlier in the waking time. The decline in performance is often referred to as “fatigue” (Åkerstedt,
2007). Performance shows a general decrease if the subject is sleep-deprived.
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15. 2.3.2.1. Modelling Effects of Performance
When exogenous components (lighting, noise, etc.) have been standardized, performance is determined by the
interaction between a circadian component (parallel to core temperature) and a decrement due to time awake;
these factors dominate models of performance.
In the two-process model (Folkard and Akerstedt, 1992), the interaction between a homeostatic component, S,
and a circadian component, C, determines alertness. The homeostatic component reflects decline of alertness
with time awake; alertness is maximal on awakening, decreases exponentially with time awake, and recovers
during sleep. SWS is a marker for this recovery. Component C is parallel to the rhythm of core temperature
(Figure 12). Although the negative effects of time awake begin soon after waking (fall of S), these are initially
opposed by the rise in C (rising core temperature). In the afternoon, the continuing circadian rise balances the
effects of time awake. In the evening, both time awake and falling circadian temperature reduce alertness.
Figure 12. The interaction between circadian (C) and homeostatic (S) processes in determining alertness during
the waking period (S+C). S‟ indicates the recuperative effects of sleep (From Borbeley, 1982).
This model allows alertness (S+C) at different times of day and after different times awake to be calculated
(Figure 13). Research based on eye movements and mental performance indicate that, if the alertness score
dropped below 7, the individual does not perform tasks adequately and safely. In the “critical” zone, there is
high risk of poor performance, and even of taking “mini-sleeps”.
One elaboration of this model is based on the observation that there is a reduction in alertness in the time shortly
after awakening, when there can also be disorientation, effects collectively known as „sleep inertia‟. Sleep
inertia is particularly marked after awakening from SWS, and this might explain why some naps seem far more
refreshing than others. Sleep inertia has little effect after 1 hour of waking and has disappeared after 3 hours.
The three-process model of alertness takes this effect (Process W) into account.
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16. Figure 13. Prediction of alertness based on two-process model of sleep regulation (From Borbeley, 1982).
These models can predict the decrement in alertness as well as the role of naps, changed sleep times and
adjustment of the body clock in reducing these decrements, and are useful in night work (Borbély et al., 2000).
Researchers are applying these concepts to models that predict effects of a variety of environmental, medical
and physical changes on a person‟s sleep and performance (Phillips, 2009).
2.3.3. Rhythms of Hormones
Circulating hormone levels also show circadian rhythms. These rhythms depend on the body clock, food intake,
postural changes, physical activity and the REM-NREM cycle.
Growth hormone (GH) secretion, for example, has a large exogenous component and is dominated by the time
of SWS rather than the circadian clock; van Cauter and Spiegel (1999) showed that there was a consistent
relationship between the appearance of SWS and GH secretion during the beginning of sleep (when process S‟
was occurring). On the other hand, cortisol secretion is regulated by the body clock, possessing a large
endogenous component, and the 24-h profile of plasma cortisol (Figure 5) alters very little when sleep times are
changed (van Cauter and Spiegel, 1999).
2.4. Summary of the Roles of the Body Clock and Circadian Rhythms
In summary, in the late night and early morning, the body clock prepares us for awakening; in the daytime, high
levels of SNS activity and core temperature enable our physical and mental performance to be at their peak; and,
in the evening, the body clock “tones us down” in preparation for sleep. Temperature and melatonin secretion
are important links in this integration between the body clock and sleep-wake cycle (Lack and Lushington, 1996;
Murphy and Campbell, 1997; Shochat et al., 1997), an integration that confers optimal health and survival
potential (Laposky et al., 2008). Altering gene expression creates dramatic changes in this circadian system;
mutants are known in animals showing body clocks that have abnormal periods, cannot be entrained by natural
zeitgebers or are even non-functional. In all cases, these animals are at a severe disadvantage ecologically
(searching for food or a mate at the wrong times of day), and are found very rarely in the field.
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17. 3. Explanation of Some of the Negative Effects of Night Work
Temporary changes in lifestyle and the environment have little effect upon the normal circadian system, as the
phase of the body clock remains unaltered. This robust property of the body clock has strong ecological value,
protecting individuals from transient changes in lifestyle (taking a daytime nap, or waking at night) or
environment (flashes of lightning at night or dark thunder clouds obscuring daylight). However, such a robust
body clock causes problems when an individual‟s sleep-wake cycle is changed less transiently, as in the days
after a time-zone transition or during night work. In these circumstances, the normal synchrony (see Figure 6)
between an individual‟s environment and lifestyle (exogenous component) and body clock (endogenous
component) is lost.
3.1. Time-zone Transitions and Jet Lag
Problems associated with this loss of synchrony will be illustrated by a brief account of changes after a time-
zone transition (summarised by Waterhouse et al., 1997, 2007). This account can then form the basis for a more
extended account and explanation of the problems associated with night work.
Loss of synchrony between the endogenous and exogenous components of a rhythm causes the symptoms of
“jet lag”, important components of which are poor sleep at night, daytime fatigue, loss of motivation and
decrements in mental performance (Edwards et al., 2000). Travellers might try to integrate their lifestyle into the
new environment, but this will no longer accord with the biological rhythms being promoted by the body clock.
To take sleep, for example: after a westward flight across 8 time zones, the individual will feel tired at 16:00 h
local time (equivalent to 24:00 h in the time zone just left, to which the body clock is still adjusted), and will
then begin to feel more alert at local midnight (08:00 h on “body time”). By contrast, after an eastward flight
across 8 time zones, the individual does not feel tired at midnight by local time (16:00 h on body time) but is
ready to sleep as the new day dawns at 08:00 h (24:00 h by body time).
Deterioration in mental performance during the new daytime occurs in the days immediately after the time-zone
transition. First, after a flight eastwards across 8 time zones, core temperature will not peak at 17:00 h but rather
at 01:00 h by new local time and, after a flight westwards across 8 time zones, at 09:00 h. The rhythm of mental
performance, paralleling core temperature, will be phased similarly, and so the individual is trying to perform
mental tasks in the new daytime at the wrong “body time”. Second, since sleep loss will be incurred and this
will further reduce mental performance.
Adjustment of the body clock is brought about by the changed timing of zeitgebers in the new time zone;
adjustment is progressive and the symptoms of jet lag abate as adjustment occurs. Some symptoms recover more
quickly than others, due to different strengths of the exogenous and endogenous components of a rhythm. For
those variables with a strong exogenous component, adjustment will be more rapid (as the traveller‟s lifestyle is
adjusted to the new time zone); for variables with a strong endogenous component, the rate of adjustment will
be slower, in line with that of the body clock. For the several hormones (with different sizes of endogenous and
exogenous component), there will be a complex mixture of rhythms showing different amounts of adjustment to
the new time zone; the normal integration that exists between these hormones will be lost.
3.1.1. Differences between Time-zone Transitions and Night Work
Adjustment of the body clock to the new time zone can be promoted by strengthening exposure to the zeitgebers
in the new environment. It is important to realise that all zeitgebers will adjust the body clock by the same
amount (equal to the change in time zone) - that is, as in normal circumstances, the time information conveyed
by all of them is identical.
During night work, problems similar to those after a time-zone transition are found, because working at night
and sleeping during the daytime does not accord with the body clock. Symptoms similar to jet lag are present -
“shiftworker‟s malaise”. Even though an inappropriate timing of the body clock dominates the reason for these
problems, they differ from those due to time-zone transitions in not being transient. Not only might night work
constitute a substantial proportion of an individual‟s working life but also the body clock is slower to adjust than
after a time-zone transition. This poorer adjustment is because the different zeitgebers no longer give
unambiguous information with regard to the appropriate timing of circadian rhythms. Even if an individual
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18. adjusts sleep times, alters the pattern of meals and is active during free time, some zeitgebers, including the
light-dark cycle and rhythms of other members of the household and the population as a whole, do not adjust.
The problem is worsened during rest days since then there is a strong tendency for the individual to conform
with the rest of society; if this happens then ALL zeitgebers act together to adjust the body clock to “normal”
time, any partial adjustment of the body clock being lost (Waterhouse et al., 2001; Waterhouse and DeCoursey,
2004).
These problems are illustrated by Figure 14. Adrenaline is a “stress” hormone, normally secreted more in the
daytime, when alertness and activity are required, and less at night, when individuals want to relax and sleep
(Figure 14A). During night work, adjustment was incomplete after one week (Figure 14B), values during the
work period (night) being too low and those during the sleep period (daytime) too high. Even after 21
consecutive night shifts (Figure 14C), values during work were still too low, even though sleep values were now
as low as during nocturnal sleep (compare sleep values in parts A and C of the Figure). However, once the
subjects reverted to a “normal” lifestyle, adjustment of the adrenaline rhythm was very rapidly lost (Figure 14D).
This last finding is of particular concern if night shifts are interspersed with rest days, when any partial
adjustment during the night shifts will be lost.
Figure 14. Daily course of urinary adrenaline excretion in shift workers during: A, the last week of day work;
B, the first week of night work; C, the third week of night work; D, the first week of returning to day work.
Mean of 15 workers. For clarity, data have been repeated beyond 24 hours. (From Minors and Waterhouse,
1981).
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19. 3.2. Night Work and Sleep
Daytime sleep averages 1-2 h less than normal, due both to external factors (noise and light) and sleeping when
core temperature is rising (Figure 5). There are also more transient wakings (Figure 1C). The distribution of
sleep stages and secretion of some hormones also changes during daytime sleep; GH secretion is still early in
sleep (due to the rhythm‟s large exogenous component) but cortisol and REM sleep appear sooner (maintaining
their normal relationship to the body clock due to their rhythms having strong endogenous components). SWS is
displaced from its normal position at the beginning of sleep but rather spans the whole of the sleep (so losing its
normal synchronicity with growth hormone secretion). That is, not only is there a change in the distribution of
sleep stages but also the normal relationships between these and endocrine secretion is lost.
3.3. Night Work and Mental Performance
Recent reviews of the problems associated with night work (Åkerstedt, 1995; Dinges, 1992; Knutson, 2003;
Culpepper, 2010; Drake, 2010) all stress the negative effects of night work upon alertness and cognitive tasks.
Deterioration in mental performance occurs for several reasons. First, individuals will be working at a time
closer to the temperature trough than its peak, so performance will be poorer and they will feel sleepy. Second,
partial sleep loss will add to these difficulties. There is a third problem. During day work, individuals work in
the first part of their waking day and relax during the second part. By contrast, in order to spend some time with
the family, night workers tend to sleep in the morning after returning from work and then meet their family in
the evening before going to work. That is, night workers tend to work in the second part of their waking span,
and cognitive tasks in particular will be negatively affected by the increased time awake. The arrows in Figure
12 show the severe performance decrement that will exist at the end of the first night shift if subjects (with
rhythms still adjusted to a diurnal lifestyle) have been awake for 24 h. With subsequent night shifts, assuming
that sleep ended about 14:00, then time awake by the end of the shift would be about 17 h; performance would
still be “critical”, particularly as effects of sleep loss would be present as well.
3.4. Differences between Individuals
Individuals do not suffer equally the negative effects associated with night work; some find it too demanding
and have to leave night work (Waterhouse et al., 2001). Predicting those who will be more susceptible, either to
warn them of possible problems or to stress to them the need to implement advice to ameliorate the difficulties,
becomes important, therefore.
3.4.1. Chronotype
Most individuals living under natural conditions of lighting and social interactions, waking at 07:00 h and
retiring at 23:00 h, show the rhythms in Figures 5 and 6 (Dijk et al., 1999; Refinetti and Menaker, 1991). There
is biological variation, of course, but interest centres on the 10% extremes of the population, the morning types
(“larks”) or evening types (“owls”).
Morning-types have earlier circadian rhythms and sleep-wake cycles than normal, while evening-types have
later circadian rhythms and sleep-wake cycles (Kerkhof, 1985; Vidacek et al., 1988). Body temperature minima
for larks and owls are closer to 03:00 h and 06:00 h, respectively. Larks are more energetic during the early
morning and become fatigued earlier in the evening; the opposite differences apply to owls. Larks prefer
morning shifts and dislike night work. Owls have difficulties in working early in the morning but still feel
energetic late in the evening, and can sleep later into the morning (Lavie and Segal, 1989); they prefer night
work to morning shifts and are less negatively affected by night work (Hildebrandt and Strattman, 1979).
The differences in phase of the temperature rhythm are retained on constant routines (Figure 15), indicating that
they are not due to the different sleep-wake habits but rather to the output of the SCN. That is, the preferred
times of sleep and wake probably reflect differences in timing of the SCN. A study of monozygotic and
dizygotic twins showed that the difference in circadian timing is inherited (Cermakian and Boivin, 2003).
19

20. Figure 15. Circadian rhythm of body temperature of morning-type (larks) and evening-type (owls) individuals
measured during constant routines (From Bailey and Heitkemper, 2001).
Measurements of the molecular rhythms from the expression of Bmal1 in larks and owls showed that about half
of the larks had significantly shorter periods than the owls, even though about half the sample had “normal”
period lengths. Therefore, not only genetic variation but also differences in timing of zeigebers and individuals‟
choice contribute to inter-individual circadian variation. Some individuals are particularly marked larks –
showing Familial Advanced Sleep Phase Syndrome - waking up on average around 0400h and falling asleep
around 1930h. This trait is caused by a mutation in the PER2 gene, (see Figure 7 and Phillips, 2009).
However, it must also be remembered that the majority of the population (80-90%) shows an “intermediate”
chronotype.
3.4.2. Resistance to Fatigue - Trototype
The term “trototype” describes differences in susceptibility to sleep loss, and genetic polymorphism is a
contributory factor. In 2009, a research team in the University of California discovered the first gene involved in
regulating the optimal length of human sleep, PER3. A mutation in this gene allows an individual to cope better
with cognitive tasks following shorter sleeps, by recruiting extra brain structures. Individuals who were
vulnerable to sleep deprivation showed, instead, a general reduction in brain activity (Bensten, 2009).
It is unclear whether an individual tolerant of night work possesses innate traits and/or has developed coping
mechanisms (which need to be more effective in those lacking the appropriate traits). What is clear is the
converse - those who need to develop such mechanisms due to lack of the appropriate traits, but cannot (or do
not wish to), are intolerant.
20

21. 4. Advice on Night Work
4.1. General Considerations
Based upon chronobiological considerations (Section 2) and their application to night work (Section 3), advice
to deal with many of the problems associated with night work (Section 1) can be given. Since this advice
follows logically from previous sections, it is summarised in Table 1 without further comment.
Table 1. Summary of advice to night workers
Sleep
Family support important in promoting daytime sleep
Bedroom must be conducive to sleep
Minimize interruptions (telephones, visitors, households)
Relax before sleeping
Leisure time
Make use of leisure time to relax the mind and body
Take advantage of no crowds for shopping or trips
Catch up on sleep
Fitness
Take regular exercise to help maintain alertness and reduce health risks
Recommended time for exercise is the late afternoon or early evening
(not early morning or late evening)
Two related issues remain to be discussed; advice regarding short sleeps and whether or not steps should be
taken to promote adjustment of the body clock to night work.
4.2. Naps
Short sleeps or naps (generally of less than 2 h duration) can be used to “top up” lost sleep. Naps can counteract
the effects of sleepiness by enhancing alertness and improving cognition (Campbell, 1992; Hayashi and Hori,
2008). Naps after sleep-deprivation are also beneficial to performance for up to 12 hours (Dinges, 1992).
Therefore, naps have been suggested to minimize any sleep debt a night worker might experience.
Two common napping strategies are: (I) to nap before the night shift (prophylactic napping) and (II) to nap
during the night shift (restorative napping). Figure 16 shows the effect of sleep deprivation and a nap on
component S of the two-component model of sleep regulation. Whereas sleep deprivation increases the intensity
of the S component, a daytime nap counteracts the rising trend of slow-wave propensity (process S), and
attenuates SWS in the subsequent nocturnal sleep (Achermann and Borbély, 2003). Scheduling multiple naps
during the day attenuates the increase of process S and the need for SWS when the full sleep is finally taken
(Werth et al., 1996; Cajochen et al., 2001). Restorative naps have been permitted in workplaces such as
hospitals and industries; a study by da Silva Borges et al. (2008) reported a decrease in sleepiness after nap in
nursing personnel working 12-hour shifts.
21

22. Figure 16. Simulation of the homeostatic process (Process S) increasing exponentially during waking and
declining exponentially during sleep. Blue: baseline with an 8-h sleep episode; red: sleep deprivation and
recovery sleep after 40 hours of wakefulness; green: 2-h nap at 18:00 h and subsequent nighttime sleep. Bars on
top indicate sleep episodes (from Tobler and Achermann, 2007).
However, not all subjects choose to nap (Dinges, 1992). Moreover, sleep inertia - which increases when
individuals are sleep-deprived and with the amount of SWS in the nap – must be taken into account. Sallinen et
al. (cited in da Silva Borges et al., 2008) concluded that naps should last no more than one hour to minimize this
risk of sleep inertia. Even so, it is important to allow some recovery time (about 10 – 15 minutes) before night
workers return to work after a nap.
4.3. To Adjust or Not to Adjust?
Since it is the inappropriately phased body clock that causes many of the problems associated with night work
(see Figures 12-14, for example), promoting clock adjustment would seem to be the best course of action – and
would bring night workers into line with travellers across time zones, for example.
Night workers need the body clock to be phase delayed, so that core temperature and mental performance
remain at higher levels during the night, and so the temperature minimum is later and allows sleep to be taken
more easily after the night shift. Based on the PRC (Figure 8), night workers should be exposed to bright light in
the first part of the night shift (before their body temperature minimum). There are several problems associated
with this protocol. First, for the light to be effective, it is important for the night worker not to be exposed to
bright light on the way home after the night shift (after the temperature minimum, which would cause a phase
advance); this can be a problem in the summer when sunrise occurs before the end of the night shift. Second,
bright light during the work period might compromise job performance and safety – reading computer screens
and seeing emergency signals, for example. A third problem is that such a protocol would take several days to
be fully effective, and so it would only be useful for night workers who perform several nights in succession;
even then, reverting to a “normal” lifestyle on rest days would cause the timing of the body clock to revert back
to normal.
Exercise could theoretically be used as a zeitgeber, but the level of exercise required is higher than many people
would be prepared to perform. Regular melatonin ingestion is another alternative, but great care must be taken
before advising taking this substance regularly due to the absence of long-term toxicology data.
22

23. 4.4. Future Work and Concluding Comments
In summary, the body clock is responsible for the endogenous components of circadian rhythms and it is
normally entrained to the external environment by zeitgebers. This body clock is very stable and is slow to
adjust to changes in the sleep-wake schedule. Various disturbances encountered by night workers can be
attributed to the body clock not being in phase with the altered sleep-wake cycle. Night work is not easily
tolerated by some, due to differences in lifestyle, commitment to the demands of night work and genetic factors.
Assessing differences between individuals and their genetic variability with regard to suitability for night work
becomes most important, therefore. Ways to measure clock-gene expression from cheek swabs are being
developed, which could provide a quick laboratory estimate of an individual‟s chronotype. Also, the
development of computer models that calculate individuals‟ ideal work schedules on the basis of their
chronotype and sleep needs are being developed (Phillips, 2009). The detailed effect of naps on brain activity,
cognition and sleep architecture need to be established (Stampi, 1992).
Finally, social problems encountered by night workers should not be under-estimated; even if individuals were
to adjust their body clock to night work, the social problems would remain. Accepting that night work is
necessary, management must understand that certain individuals will suffer. Regular health checks and
counselling services should be possible, to ensure the well-being of night workers. If a worker is found to have
problems that cannot be resolved by counselling, then transfer out of night work should be possible without
prejudice.
23

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