Why do we tire? Part 2

 (B) Circadian rhythm disorders  

https://en.wikipedia.org/wiki/Circadian_rhythm_sleep_disorder
https://www.nhlbi.nih.gov/health-topics/circadian-rhythm-disorders

This family of sleep disorders influence the timing of sleep. They manifest from a persistent pattern of sleep/wake disturbances as a result of either dysfunction in an individual’s biological clock system, or misalignment between an individual’s endogenous oscillator and externally applied cues. This mismatch increases the tendencies to fall asleep at unconventional times of the day. These occurrences often lead to recurring instances of disturbed rest, increasing the difficulty to fall asleep and the tendency to awaken at “normal” times for work, school, and other social commitments. 

1. Advanced sleep phase disorder 

https://en.wikipedia.org/wiki/Advanced_sleep_phase_disorder

• Also known as advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder, ASPD is a sleep condition that features a recurrent pattern of early evening (e.g. 7-9 pm) sleepiness and early morning awakening.
• ASPD patients are unable to stay awake until conventional bedtime, tend to fall asleep in the evening, and are unable to fall asleep until their desired waking time, suffering early morning insomnia. This suggests their melatonin levels and core body temperature cycle hours earlier than an average person.
• To diagnose for ASPD, sleep specialists measure the patient's sleep onset and offset, dim light melatonin onset, and evaluate their Horne-Ostberg morningness-eveningness questionnaire results. Additional methods include a polysomnography test to rule out other sleep disorders such as narcolepsy, as well as accounting for the patient's age and medical history. 
• It is estimated ASPD affects about 1% in middle-age adults, which affects both men and women equally. A 2012 study found a solid familial tendency in regards to ASPD, with about 40-50% of affected individuals having relatives with ASPD. One form of ASPD called familial advanced sleep phase disorder (FASPS) has links to missense mutations in genes hPER2 and CKIΔ. 

i. Familial Advanced Sleep Phase Syndrome 

-- Symptoms 

• Patients fall asleep and wake up 4-6 hours earlier than the average population, who sleep from around 7:30pm to 4:30am. 
• A free running circadian period of 22 hours, which is significantly shorter than the average human period i.e. 24 hours. 
• Their sleep deprivation may be inflicted by social norms causing patients to delay sleep until a socially acceptable time, which results in them losing sleep due to earlier-than-usual wakeup time. 
• Roughly 50% of directly related family members experience the symptoms of FASPS, which indicates an autosomal dominant trait. 

-- Who discovered it? 

• This disorder was first observed by Louis Ptáček at the University of Utah in 1999, who studied patients with "disabling early evening sleepiness" and "early morning awakening". He hypothesised the allele linked to FASPS elicited a quantitatively greater effect on clock function compared to more common genetic variations. 
• In 2001, the Phyllis C. Zee research group found a familial link between ASPS and changes to circadian timing rather than an exogenous disruption of sleep homeostasis. Moreover, they discovered that the family of interest contained an ASPS-affected member in every generation, which indicated the phenotype segregates as a single gene with an autosomal dominant mode of inheritance. 
• In 2001, Ptáček and Ying-Hui Fu research groups published a paper on the genetics of FASPS that concluded a mutation in the CK1-binding region of PER2 resulted in the FASPS behavioural phenotype. 

-- What are the causes? 

• Studies proposed a model of the FASPS genetic map involving the Period2 (Per2) and Casein Kinase I (CK1) binding domain of the hPER2 protein. 
• Per2 is a mammalian gene associated with the maintenance of circadian rhythms. A serine-to-glycine point mutation in the Casein Kinase I (CK1) binding domain of the hPER2 (h = human) protein was observed to result in hypophosphorylation of hPER2 in vitro. This disrupts the transcription-translation (negative) feedback loop (TTFL) responsible for regulating the stable production of hPER2 protein. 
• This reduces the amount of Per2 mRNA being transcribed and the circadian period decreases to less than 24 hours (around 22 hours). 
• Although a 22 hour circadian period doesn't always lead to a phase shift, it can be predicted depending on the time the subject is exposed to the stimulus, represented on a Phase Response Curve (PRC).
• In 2005, a mutation in CKIδ (a functionally redundant form of CK1ɛ in the phosphorylation process of PER2) was observed by Fu and Ptáčekto cause symptoms of FASPS. Xu et al. (2007) found an A-to-G missense mutation substituted threonine for an alanine in the protein structure, which reduced phosphorylation of PER2. 
• Genetic studies on the Per2 S662G mutation of CKIδ revealed it results in hypo- or hyperphosphorylation of the Per2 gene depending  on the binding site on Per2 that CK1δ interacts with. 

2. Cyclic alternating pattern (CAP)

https://en.wikipedia.org/wiki/Cyclic_alternating_pattern

This is an EEG of a Cyclic Alternating Pattern (CAP). Reproduced with the permission of M.G. Terzano. The top part shows the Cyclic Alternating Pattern in Stage 2 sleep, with the two different phases A (EEG activation) and B (EEG deactivation). Phase A and B composes a cycle and 60 s equals to a sequence. The bottom part represents a Non Cyclic Alternating Pattern (NCAP) period of sleep, corresponding to sleep stability. The recordings are shown from frontal, central and occipital leads. In addition, the figure displays EOG and EMG, EKG (heart rate), abdominal (O-N PNG) and thoracic (THOR) respiratory efforts as well as both right and left tibialis (respectively TIB ANT R and TIB ANT L). 

• This sleep condition is characterised by 2 long-lasting alternate electroencephalogram (EEG) patterns during sleep. 
• A 2014 study by Parrino et al. suggested this pattern indicates the sleeping brain reorganising its neural connections whilst it is being challenged by alternating environmental conditions. This demonstrates periodic abnormal electrocortical activity with a recurring frequency of up to 1 minute. 
• Eisensehr et al. (2001) found CAP in Lennox-Gastaut syndrome mediates the occurrence of clinical seizures and generalised epileptic discharges through a gate-control mechanism. 
• CAP is regarded as a marker of NREM instability, as well as a "master clock" that coincides with the stage transitions maintained in sleep phases, indicated by both EEG and by autonomic functions through regular fluctuations. 
• A 2018 study found CAP is reduced in narcolepsy, multiple system atrophy, as well as some instances of drug administration, with CPAP treatment for OSA, and during night-time recovery sleep after prolonged sleep deprivation. 
• A 2018 report asserted the association between CAP and neurovegetative fluctuations and motor events regulates the pathophysiology of several sleep disorders and the effect of medication on continuous positive airway pressure (CPAP) treatment. 

3. Delayed sleep phase disorder (DSPD)

https://en.wikipedia.org/wiki/Delayed_sleep_phase_disorder

• Often referred to as delayed sleep phase syndrome or delayed sleep–wake phase disorder, this chronic condition is characterised by a dysregulated circadian rhythm relative to that of a normal person. 
• It impacts a multitude of functions related to the circadian rhythm such as the core body temperature timing of sleep, peak period of alertness, rhythm, hormonal as well as other daily cycles. 
• It was first observed by Elliot D. Weitzman and others at Montefiore Medical Center in 1981. However, this condition tends to remain untreated or receive inappropriate treatment, or often misdiagnosed as primary insomnia or as a psychiatric condition.
• Using the ICSD-1 diagnostic criteria (current edition ICSD-3), studies estimated the prevalence of DSPD to be between 0.17% and 0.7%. 
• A 2014 study used a modified version of the Munich Chronotype Questionnaire and concluded the prevalence of DSPD ranged from 1.5% to 8.9% depending on the strictness of the definition used. 
• Carskadon (2008) stated both circadian phase and homeostasis contribute to a sleep condition similar to DSPD in post-pubertal as compared to pre-pubertal youngsters. 
• Danielsson et al. (2016) and Saxvig et al. (2012) suggested DSPD is more prevalent among adolescents across cultures and across mammalian species, which suggests an association with puberty rather than age. Studies estimated about 3.4% to 8.4% high school students are diagnosed with DSPD. 

What are the symptoms of DSPD? 

i. Comorbid symptoms 

• Clinical depression or other psychological problems (50% of patients) 
• Attention deficit hyperactivity disorder (ADHD) = Polymorphisms in genes involved in both ADHD and circadian rhythm 
• Increased body weight 
• Obsessive–compulsive disorder

ii. Presenting symptoms 

• Inability to sleep until the early morning
• Falling asleep around the same time every day 
• Difficulty in waking up in time for a typical school or work day 
• If they are allowed to stick to their own sleep schedules, their sleep quality improves and they avoid excessive daytime sleepiness. 
• Social jet lag 

What are the causes of DSPD?  

• The cause of DSPD is currently unknown and researchers don't know for certain what causes the abnormality in the biological clocks of DSPD patients. 
• Since DSPD runs in families across generations, researchers implicated the hPer3 (human period 3) and CRY1 genes contributes to the symptoms of DSPD. However, more research is required to understand the biological and genetic causes of DSPD. 

How is DSPD diagnosed? 

It can be diagnosed using actigraphy, polysomnography, a sleep diary, or by a clinical interview. If we incorporate minor updates to the ICSD-3 in 2014, the diagnostic criteria for DSPD includes: 

• 1. An intractable delay in the phase of the major sleep period occurs in relation to the desired clock time, as evidenced by a chronic or recurrent (for at least three months) complaint of inability to fall asleep at a desired conventional clock time together with the inability to awaken at a desired and socially acceptable time.
• 2. When not required to maintain a strict schedule, patients exhibit improved sleep quality and duration for their age and maintain a delayed phase of entrainment to local time.
• 3. Patients have little or no reported difficulty in maintaining sleep once sleep has begun.
• 4. Patients have a relatively severe to absolute inability to advance the sleep phase to earlier hours by enforcing conventional sleep and wake times.
• 5. Sleep–wake logs and/or actigraphy monitoring for at least two weeks document a consistent habitual pattern of sleep onsets, usually later than 2 am, and lengthy sleeps.
• 6. Occasional noncircadian days may occur (i.e., sleep is "skipped" for an entire day and night plus some portion of the following day), followed by a sleep period lasting 12 to 18 hours.
• 7. The symptoms do not meet the criteria for any other sleep disorder causing inability to initiate sleep or excessive sleepiness.
• 8. If one of the following laboratory methods is used, it must demonstrate a significant delay in the timing of the habitual sleep period: 1) 24-hour polysomnographic monitoring (or two consecutive nights of polysomnography and an intervening multiple sleep latency test), 2) Continuous temperature monitoring showing that the time of the absolute temperature nadir is delayed into the second half of the habitual (delayed) sleep episode.

The ICSD's severity criteria include: 

-- Mild = 2-hour delay (relative to the desired sleep time) linked to little or mild impairment of social or occupational functioning.

-- Moderate = 3-hour delay linked to moderate impairment

-- Severe = 4-hour delay linked to severe impairment 

Distinguishing features of DSPD compared to other sleep disorders include: 

-- At least a normal ability to sleep during the morning, and occasionally in the afternoon

-- Falling asleep at more or less the same time every night, and sleep occurs quite rapidly if the person goes to bed near the time they usually fall asleep. Young children take longer to sleep if they enter the bed before they are sleepy. Nonetheless, they eventually fall asleep if they are permitted to stay up until the time they usually fall asleep.

-- Patients' quality of sleep is satisfactory and at the regular time when they can follow their own sleep schedule

-- It's a chronic condition with symptoms present for at least 3 months before a diagnosis of DSPD can be confirmed. 

How can DSPD be managed? 

i. Non-pharmacological 

• Phototherapy (Light therapy): Either a bright white lamp providing 10,000 lux at a specified distance from the eyes, a wearable LED device providing 350–550 lux at a shorter distance, or natural sunlight. Light is shone around 30–90 minutes at the patient's usual time of spontaneous awakening, which corresponds to the phase response curve (PRC) for light. 
• Scototherapy (Dark therapy): Limiting light exposure in the evening 
• Phase delay chronotherapy = Aims to reset the circadian clock by manipulating bedtimes. It comprises of entering the bed 2 or more hours later each day for several days until the desired bedtime is reached. The process is repeated every few weeks or months to maintain results. 
• Controlled sleep deprivation with phase advance (SDPA) = A modified version of chronotherapy that involves the patient staying awake one whole night and day, then sleeping 90 minutes earlier than usual and maintains the new bedtime for a week. This routine is repeated  weekly until the desired bedtime is achieved.

ii. Pharmacological 

• Aripiprazole (Abilify) = An antipsychotic that helps advance sleep onset, sleep midpoint, and sleep offset at relatively low doses. 
• Melatonin doses = Administrated an hour or so before the usual bedtime in order to induce sleepiness. They may help reset the body clock. Side effects include sleep disturbance, nightmares, daytime sleepiness, and depression
• Modafinil (Provigil) = An approved stimulant to treat shift-work sleep disorder, which shares some symptoms of DSPD. 

4. Irregular sleep-wake rhythm

https://en.wikipedia.org/wiki/Irregular_sleep%E2%80%93wake_rhythm

• This rare form of circadian rhythm sleep disorder features frequent naps throughout the 24-hour period, no main nighttime sleep episode and irregularity from day to day. 
• Patients lack a pattern of wakefulness and sleepiness, exhibit poor quality sleep, and experience drowsiness even awake. 

What are the causes of ISWR? 

• It appears as a symptom of neurological disorders such as dementia (particularly Alzheimer's Disease), brain damage, or intellectual disabilities.
• It suggests the risk for this disorder increases with age, but only due to increased prevalence of co-morbid medical disorders.

How is ISWR diagnosed? 

• A sleep diary is used to aid in diagnosis and to record the sleep schedule during treatment. 
• Actigraphy can be used to monitor the sleep schedule. 
• Continuous Positive Airway Pressure (CPAP) machine

Signs to look for include: 

-- Sleeping on and off in a series of naps during the day and night, with no regular pattern but with normal total sleep time. 

-- Difficulty achieving restorative sleep

-- Excessive daytime sleepiness 

• First visit with sleep physician involves asking the patient their medical history, which includes alcohol use, family history, any neurological problems, any prescription or non-prescription medications consumed, or any other sleep problems. The patient is then instructed to complete a sleep diary, recording natural sleep and wake up times. The Epworth Sleepiness Scale is used to appraise the patient's quality of sleep. 
• Medical tests include polysomnography, blood tests, a CT scan or an MRI. These may detect other sleep disorders, such as sleep apnea and periodic limb movement disorder. 

How is ISWR managed? 

• Sleep hygiene education 
• Melatonin, vitamin B12, sleep aids, wake aids, and other medications
• Exposure to light during the daytime and activities occurring at regular times each day to aid in readjusting the circadian rhythm. 
• The best treatments for each ISWR patient varies for different subgroups. For example, those also afflicted with dementia aren't prescribed sleep-promoting medications (sedatives) for ISWD due to the increased prevalence of adverse effects. 

5. Jet lag 

https://en.wikipedia.org/wiki/Jet_lag

Let's say you departed London at 11 am Tuesday. The flight is about 3 hours long (excluding time zone differences), therefore you land in New York at 2 pm Wednesday London time. However the time in New York is 5 hours ahead of London, so the actual time in New York is 7 pm Wednesday New York time. Whenever you have travelled on a long-haul flight between 2 major cities such as New York and London, have you experienced those feelings of fatigue and difficulty sleeping associated adjusting between 2 drastically different time zones?

This is known as jet lag. 

What are the signs and symptoms of jet lag? 

• Sleep disturbances along with poor quality of sleep upon arrival, as well as trouble falling asleep (when flying east), early awakening (when flying west), and trouble remaining asleep. 
• Cognitive effects such as reduced performance on mental tasks and concentration
• Confusion 
• Dizziness 
• Anxiety
• Insomnia 
• Irritability 
• Issues with digestion e.g. indigestion, alterations in frequency of defecation and consistency of faeces, decreased interest in and enjoyment of food 
• Headaches 
• Fatigue 
• Nausea 

Travel fatigue (caused by a disruption in routine, time spent in a cramped space with minimal wriggle room, and a low-oxygen environment): 

• General fatigue 
• Disorientation 
• Headache 
• Dehydration (due to dry air and limited food and drink) 

What are the causes of jet lag? 

• Double desynchronisation = When the circadian rhythm is out of sync with the day–night cycle of the destination you landed in. 
• Internal desynchronisation = When people travel across several time zones, their sleep–wake cycles adapts with the light from the environment within a few days. However, their skeletal muscles and internal organs adapt at different rates. 
• Delayed sleep phase disorder 

Which flights have highest likelihood of jet lag? 

• Over the Arctic Ocean or the North Pole (often the shortest route between northeast Europe and Alaska or the Canadian West Coast and East Asia). e.g. Between Alaska and northeast Europe
• Flights that cover high trans-meridian (west–east or east–west) distance e.g. Between Los Angeles, CA and Miami, FL in the USA (east-west) 

How is jet lag managed? 

i. For people travelling east 

If you're travelling east by 6 to 9 time zones, Waterhouse et al. (2007) advised you to avoid light in the mornings. 

If you are travelling east by at least 10 hours, it is advised to assume a 14-hour westward transition and delay your body clock. 

ii. For people travelling west 

These flights are less likely to cause jet lag, therefore it is adequate to seek light during the day and avoid it at night. It is advised to set up later sleep times the days before, travel during the daytime, sleep a few hours onboard the flight in order to minimise fatigue at arrival and during ground transfer.

iii. Other methods 

-- Timed light exposure 

• Assuming you adhere to the correct timing, this method aids in matching your circadian rhythm with the expected cycle at their destination. It helps advance or delay a circadian phase expected to be active at the destination. 

-- Melatonin treatment 

• It is more effective for eastward flights than for westward ones since it is more efficient to to delay than to advance the circadian rhythm. However, its effects on the consumer are contentious, thus anti-doping agencies limit or prohibit its use for athletes. 
• Piérard et al. (2001) found evidence that melatonin consumption combined with monitoring circadian phase decreased jet lag symptoms and advanced realignment of the circadian clock. 

-- Adjusting sleep schedules 

• For shorter trips, it is advised to maintain the sleep-wake schedule from home after arriving at the destination. 
• If this isn't practical, it is recommended to adjust your sleep schedule before departure by 1 to 2 hours to match the destination time zone. 

-- Pharmacotherapy 

• Hypnotic medication such as zolpidem can improve sleep quality and decrease the chance of waking up during deep sleep as one travels across 5 to 9 time zones. However, be aware of potential side effects of hypnotics such as amnesia and confusion, e.g. triazolam. 

6. Non-24-hour sleep-wake disorder (N24SWD)

https://en.wikipedia.org/wiki/Non-24-hour_sleep%E2%80%93wake_disorder

https://jcsm.aasm.org/doi/10.5664/jcsm.7054

https://www.frontiersin.org/articles/10.3389/fneur.2016.00017/full

• This chronic circadian rhythm sleep disorder is defined as a chronic steady pattern comprising X daily delays in sleep onset and wake times in an individual living in a society. 
• In November 1970, Ann L. Eliott et al. published the first report of a N24SWD case, which described an American man who on 26-hour days. 
• In 1977, Miles Le and co. conducted the first detailed study of N24SWD in a blind subject, who was a 28-year-old male that had a 24.9-hour rhythm in sleep, plasma cortisol, and other parameters. 
• In 1983, Redman et al. first demonstrated rats that were administered melatonin had entrained free-running rhythms in a time-free environment. Subsequent researchers supported this finding that appropriately timed melatonin administration could entrain free-running rhythms in completed blind mice, which indicated endogenous melatonin can play the role of  a marker for circadian rhythms. 
• A review of the research studies found melatonin dosage of about 5 mg was sufficient in entraining free-running rhythms in N24SWD patients. 
• Since the 1980s, a number of melatonin receptor agonists were created to offer short-term treatment for the symptoms of N24SWD. Examples of agonists include ramelteon (Rozerem), melatonin prolonged-release (Circadin), tasimelteon (trade name Hetlioz) and TIK-301. 

What are the causes of N24SWD?

i. Sighted patients 

• N24SWD sufferers experience difficulties adapting to changes in "regular" sleep–wake cycles such as evening activities, daylight savings, holidays / vacations, overseas travel to different time zones, illness, stress, medications (e.g. stimulants, sedatives), changes in daylight hours in different seasons and growth spurts. 
• It's reported their bodies deemed the length of a day (and night) is considerably longer or shorter than 24 hours and resists adjusting to the  the external light–dark cycle. 
• This disorder negatively impacts their function in school, in employment, and in their social lives. Whenever sufferers attempt to keep conventional hours, they experience insomnia and excessive sleepiness, which increases the risk of microsleeps. 
• If they are determined to live to a normal workday, they tend to express more physical and psychological complaints during waking hours, such as fatigue, headache, sleepiness, decreased appetite, or depressed mood. 

ii. Blind patients 

• Studies estimated more than 50% of all N24SWD patients are completely blind. Although it can affect patients at any age, from birth onwards, the disorder generally manifests from loss or removal of their eyes. 
• If light doesn't reach the retina, the suprachiasmatic nucleus (SCN) in the hypothalamus isn't signalled to synchronise the circadian rhythm to the 24-hour social day, which results in N24SWD for numerous blind individuals. 

What are the symptoms of N24SWD? 

• Apraxia
• Cognitive dysfunction 
• Concentration issues 
• Confusion
• Depressed mood 
• Diarrhoea 
• Nausea 
• Fatigue 
• Hair loss 
• Headaches 
• Imbalance 
• Photosensitivity 
• Arthritis 
• Ataxia 
• Hallucinations 
• Menstrual irregularities 
• Muscle pain 
• Suicidal thoughts 
• Weight gain 

How prevalent is N24SWD? 

• In the European Union, an estimated 140,000 people have N24SWD (blind and sighted), which simplifies to an approximate prevalence of 3 per 10,000, or 0.03%. The European portal for rare diseases, called Orphanet, classifies N24SWD as a rare disease, with less than 1 affected person for every 2000 people. 
• Auger et al. (2015) estimated about 70% of N24SWD patients are completely blind. Of the 1.3 million blind people in the USA, roughly 10% have no light perception at all. Moreover, approximately 50% to 75%, or 65,000 to 95,000 Americans are diagnosed with N24SWD. 

How is N24SWD diagnosed? 

• Assessment of medical history of persistently delayed sleep onset that follows a non-24-hour pattern. Sufferers' average day length is about 24.9 ± 0.4 hours (with the range of 24.4–26.5). 
• Actigraphy: This device tracks periods of sleep and wakefulness over time and visualises the progressive delay in the sleep-wake cycle that indicates signs of N24SWD. Below are case studies of an N24SWD patients' sleep habits over a several-week period. 

• Polysomnography: This is used to rule out other sleep disorders with similar symptoms. 
• Questionnaires: Morningness-Eveningness Questionnaire (MEQ) 

What are the best treatments for N24SWD?

• Tasimelteon: Approved by the FDA in 2014, this drug increased entrainment in blind subjects safely and effectively by 17%. It is a a selective agonist for the melatonin receptors MT1 and MT2, which aims to improve sleep timing. Common side effects include headache, somnolence, nausea (feeling sick) and dizziness. 
• Melatonin administration: Recommendation is administered 1 hour before before bedtime.
• Light therapy: This involves shining a bright 1000 lux white light or about 400 lux blue light on awakening to offset the tendency for circadian rhythms to delay. 
• Dark therapy: This involves filtering blue light and permitting red light with low lux. 

What is the phase response curve? 

https://en.wikipedia.org/wiki/Phase_response_curve

https://www.circadiansleepdisorders.org/info/PRC.php

This curve illustrates the relationship between a stimulus (e.g. light exposure) and a phase response (e.g. a shift in circadian rhythm, i.e. phase shift). 

A PRC for a one hour light pulse using white light at 8,000 lux from fixtures covering the ceiling, and measured for normal sleepers.

• The horizontal axis is the time of the exposure, measured in hours, with zero at Dim Light Melatonin Onset (DLMO). Normal sleepers, on average, would fall asleep about 2 to 3 hours after DLMO and wake up about 10 - 11 hours after DLMO.
• The vertical axis is the measured phase shift in circadian rhythm. A phase advance (shift to an earlier time) is up (positive numbers) on the chart. 
• The point in red corresponds to light used on awakening. It leads to an average of only 15 minutes of phase advance. 
• Light 6 hours later leads to a phase shift, about 30 mins advance. However, the light generates a phase advance even when used in the early afternoon. 
• The green dot indicates a two hour phase delay (pushes the circadian clock later) after the same amount of light (in the evening). 
• The black horizontal dashed line indicates the average subject's rhythm delay over the three day course of the phase shift measurement relative to the average period of the circadian rhythm in normal sleepers (i.e 24.18 hours), which is roughly 30 mins or 0.54 hours. 

• The red dot illustrates the result of curve fitting primarily to data from four subjects, shown inside the green oval.
• One recorded a delay of about 30 mins, one had no change, and two recorded advances of about an hour. This results in an average of 15 minute advance. 

• This graph illustrates a curve about light on awakening advancing one's circadian clock by nearly 2 hours (red dot) - but that's with 6.7 hours exposure, and a forced advance of sleep time. 
• The numbers below the original axis represent approximately the time relative to DLMO for comparison. It is based on a typical DLMO being at roughly 7 hours before CBTmin.
• The red point at the maximum advance occurring around 4 hours after CBTmin indicates light stimulus induces a phase advance of about 2 hours.
• Note that this time refers to the midpoint of the 6.7 hour light exposure, hence the light exposure actually occurred about 30 mins after CBTmin, before the subject's normal wake up time.

• This graph illustrates phase shift during three days of exposure to 185 lux blue light, which advances one's phase by nearly an hour. The light produced an advance even when used in the early afternoon.

• This plot graph of the individual data points illustrates the variability among individuals, which leads to this PRC. 
• The individual data points were collected into "bins" 3 hours wide, and all the data points in the bin were averaged together. The resulting values were plotted at the midpoints of the bins, and straight lines were illustrated between these points, to produce the previous graph. 
• There is no dot on the chart for starting light immediately on arising (i.e. about 11 hours after DLMO). There is a point for light exposure 12 hours after DLMO, which corresponds to about an hour after arising. Note this point itself is an aggregate includes a 3-hour window of start times.

• This graph illustrates phase shift during three days of melatonin administration, so one day would only shift about a third as much. For 0.5 mg melatonin (dark solid line), the maximum advance over three days was about 1.5 hours. It reached that value when the melatonin was administered about 6 hours before bedtime (red dot).
• The horizontal axis is the time, with the zero at Dim Light Melatonin Onset (DLMO), similar to the 1 hour light PRC. 
• The thin line (topmost curve) represents the natural (endogenous) secretion of melatonin.
• The dotted curve is based on a similar study but the melatonin dosage used was 3 mg. 
• Although the phase advances are similar for the two doses, the larger dose is best administered earlier in the day, however it leads to more drowsiness during the evening. 

• Another plot from the same paper is included that represents the individual data points from different subjects, which illustrates the variability of individual responses. 
• e.g. Around the peak phase advance of 1.5 hours on average, different individual subjects advanced anywhere from 0 to 3 hours.

-- CBT - Core Body Temperature

-- DLMO - Dim Light Melatonin Onset

-- PRC - Phase Response Curve

7. Shift work sleep disorder (SWSD)

https://en.wikipedia.org/wiki/Shift_work_sleep_disorder

• This circadian rhythm sleep disorder manifests in those who work long hours overlapping with their typical sleep period. 

How prevalent is SWSD? 

• It is unclear how prevalent SWSD is the general population because it is underdiagnosed and the definitions of this disorder vary in the medical literature. 
• It's estimated about SWSD affects roughly 2–10% of general population and about 27% of night and rotating workers. 
• If we follow the third edition of the International Classification of Sleep Disorders (ICSD-3) criteria, this reduces the prevalence estimates of SWSD compared to the old ICSD-2 criteria after 2014. 

What are the symptoms of SWSD? 

• Insomnia 
• Excessive sleepiness 
• Difficulty sleeping 
• Loss of concentration 
• Headaches 
• Lethargy 

What are the health impacts of SWSD? 

• Decreased bone mineral density, increased risk of fracture. Feskanich et al. (2009) found long-term shift workers in night roles, such as nurses, have elevated risk of wrist and hip fractures. 
• Low fertility and issues during pregnancy
• Obesity 
• Diabetes 
• Insulin resistance 
• Elevated body fat levels
• Dyslipidemias 
• Increased risk of mental disorders, such as depression, anxiety, and alcohol use disorder. 
• Acute sleep loss lead to increased levels of t-tau in blood plasma. 

i. Decreased quality of sleep 

• About 49% of nurses reported getting less than the recommended 7 hours of sleep per day, which is an increase of 21% compared to American national figures. 
• Links to impaired cognitive performance, including lack of focus and concentration, and slower reaction times. 
• Increased risk of poor decision-making and hazardous transport events. 
• Decreased well-being and happiness 
• Decreased quality of life based on a SF-36 assessment

ii. Sleep loss and decreased alertness 

• Decreased total sleep time (TST) and increased sleep deficit before morning shifts lead to decreased objective sleep efficiency, decreased sleep compensation over the work-free days, increased sleep latency, hence decreased sleep quality. 
• Increased incidence of attentional lapses at the beginning of night shifts
• Increased risk of a fatal workplace accident, as well as reduced productivity, increased chance of absenteeism. 
• Decreased attention span, increased microsleeps, delayed psychomotor response, decline in work performance, neglect of activities, reduced working memory. 

iii. Decreased immune function 

• Increased concentration of pro-inflammatory markers such as IL-8, and decreased concentration of anti-inflammatory markers, such as IL-10 (plays a role in tumour suppression). 
• Reduced levels of Natural Killer cells, hence weakened innate immune response and reduced tumour suppression 
• Increased risk of the common cold, as well as developing infectious diseases after exposure 
• Increased concentration of TNF, a marker of systemic immune functioning. 

iv. Increased risk of cardiovascular disease 

• Elevated levels of CRP, a marker of cardiovascular disease
• Increased risk of hypertension due to prolonged stimulation of the nervous system 

v. Occupations with higher risks of SWSD 

• Nurses 
• Truck drivers 
• Pilots 
• Train drivers 
• Firefighters 
• Doctors 
• Paramedics 
• Bartenders 
• Labour workers 
• Caregivers
• Call centre workers
• Death care workers 
• Police officers 
• Emergency medical workers 
• Casino workers 
• Funeral workers 
• Hospitality workers 
• Ship crew 
• Manufacturing workers 
• Military officers 
• Miners 
• Nuclear power workers 
• Fossil fuel industry workers 
• Solar, wind, and hydropower workers 
• Retail workers 
• Radio broadcasters 
• TV show hosts 
• News broadcasters 
• Actors / Actresses 
• Journalists 
• Security guards 
• Weather forecasters / Meteorologists 

What are the causes of SWSD? 

• Symptoms of SWSD are associated with the misalignment between the timing of a non-standard wake–sleep schedule and the endogenous circadian sleep-wake rhythm. 
• Although SWSD can people of all ages, those aged 50 years and older are at a higher risk. 
• Since a majority of female night-shift workers demonstrate sleepiness at work, it is theorised their social obligations increased their susceptibility to SWSD.  

Describe the mechanism of SWSD 

• Circadian misalignment occurs when the body doesn't adapt to a night shift schedule. This suggests the hormones cortisol and melatonin lack entrainment to a night oriented schedule, as they are still entrained on a day oriented schedule. 
• Boivin & Boudreau (2014) found melatonin levels peak at night during a shift workers awake time and decreases during a shift workers sleep time, and vice versa for cortisol levels. 

How is SWSD diagnosed? 

According to criteria of SWSD in the International Classification of Diseases (ICD-10), in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and in the International Classification of Sleep Disorders (ICSD) – Second and Third Editions, diagnosis of SWSD requires the following: 

1. Insomnia and/or excessive sleepiness with decreased total sleep time, all combined with an overlap of work period occurring during the habitual sleep time.
2. These symptoms were present for at least 3 months and are associated with the shift work schedules.
3. Sleep log and/or actigraphy monitoring (with sleep diaries) demonstrate for more than 14 days (work and free days included) circadian and sleep-time misalignment.
4. Sleep disturbance is associated with impairment of social, occupational, and/or other waking functioning.
5. These symptoms are not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, poor sleep hygiene, or substance use disorder.

Tools used to assess patients for SWSD: 

• Sleep diary 
• Morningness-Eveningness Questionnaire 
• Actigraphy 
• Polysomnography 
• Pittsburg Sleep Quality Index 

How can SWSD be treated? 

• Prescribed sleep / wake scheduling 
• Bright light treatment 
• Melatonin treatment 
• Medications that promote alertness such as caffeine, and non-amphetamine alerting drugs (e.g. Modafinil, armodafinil) 
• Medications that promote daytime sleep, such as hypnotics (e.g. Zopiclone) 

Why do we sacrifice sleep just to finish our work / study (i.e. pull an all-nighter)? 

https://www.psu.edu/news/research/story/why-do-we-sacrifice-sleep/

https://www.sleepfoundation.org/sleep-hygiene/revenge-bedtime-procrastination

https://en.wikipedia.org/wiki/Bedtime_procrastination

https://www.frontiersin.org/articles/10.3389/fpsyg.2014.00611/full

https://www.frontiersin.org/articles/10.3389/fnins.2019.00963/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460337/

Have you ever pulled an all-nighter or stayed up past your scheduled bedtime just to complete your assignment, finished a paper or work task, revise school content for tomorrow's exam, catch up watching episodes of a subscription TV / film series, chat to your partner / best friend or scroll through your social media news feed? I'm certainly guilty of doing at least one of those activities past my schedules bedtime, as are many of you as children. 

According to Penn State Associate Professor Orfeu Buxton, each of us have its own list of demands, priorities and social activities to fit into a tight daily schedule. However, despite the scientific literature advocating for 8 hour sleep every day due to the benefits it brings to our mental health, cognitive and physical function, too many people don't seem to view sleep as a priority. Why is this the case? 

To understand this behaviour, we need to dig deep into the mind, especially when it is occupied with a task during night time. Psychologists label this behaviour as bedtime procrastination or revenge bedtime procrastination. 

• It refers to people staying up later than they desire in order to control their actions over the night because they perceive themselves (subconsciously) to lack impact on the events during the day. 
• It depicts the choice of sacrificing sleep for leisure time prompted by a daily schedule deprived of free time. 
• The use of the term 'revenge' in bedtime procrastination became popular in China during the late 2010s, probably referring to the 996 working hour system (72 hours per week) i.e. 9am - 9pm, 6 days a week. It may refer to the desire of taking control over their daytime self. 
• The phrase "bedtime procrastination" was popularised by a 2014 study conducted in the Netherlands by Kroese et al. This term has resonated with many people worldwide and gained traction in response to stress triggered by the COVID19 pandemic. 
• In 2020, Daphne K. Lee described this behaviour on Twitter as "a phenomenon in which people who don't have much control over their daytime life refuse to sleep early in order to regain some sense of freedom during late night hours."

How prevalent is bedtime procrastination?

• It is highly prevalent in university / college students and women, particularly with an evening chronotype. 
• It is theorised extended work hours and lack of free time combined increased stress levels and sleep procrastination in approximately 40% of people during the pandemic. 

What are the signs and symptoms? 

• Reduced overall sleep time every night 
• No valid reason to stay up late (such as location or illness)
• Awareness of the negative effects of sleep loss, but indifference in changing their routine. 

What are the causes? 

• Risk factors include daytime stress, extended work hours, lack of free time for entertainment or relaxation.
• Surveys concluded COVID-19 and stress associated with stay-at-home orders extended work hours, which decreased normal leisure time since the pandemic started.

Describe the psychology of bedtime procrastination 

https://en.wikipedia.org/wiki/Value-action_gap

• People who undergo bedtime procrastination understand and desire adequate sleep, but fail to do so. Psychologists describe this behaviour as the value-action gap, which is defined as the failure to translate intentions into action. 
• This theory suggests a lack of self-control or self-regulation due to a busy daily schedule leads a natural tendency for bedtime procrastination. 
• However, it doesn't explain the presence of "night owls" who adapt to schedules catered for “early birds". Other psychologists argue revenge bedtime procrastination isn't mainly due to lack of self-control, but instead an attempt to set some time to alleviate stress. 
• Nevertheless, more research is required to have a greater understanding of sleep procrastination, which may be caused by multiple interacting factors such as chronotype, daytime stress, and difficulties in self-regulation.
• A 2020 exploratory study by Magalhães et al. found bedtime procrastination associated with people waking up and having dinner later than usual, whereas While-in-Bed Procrastination associated with the male gender, a desire to sleep later than usual, and having dinner earlier than usual. 

What are the effects of bedtime procrastination? 

• Sleep deprivation -- Detrimental effects on the body and mental health 
• Deteriorates thinking, memory, and decision-making 
• Increases risk of daytime sleepiness, which negatively affects productivity and academic achievement. 
• Irritability and other issues associated with emotion regulation 
• Weakens immune function and decreases the effectiveness of vaccines 
• Decreased self-regulation and impulse control, which worsens the negative cycle of decreased sleep and overall health. 

How can bedtime procrastination be managed? 

• A healthier sleep hygiene, i.e. healthier sleep habits, fostering an environment conducive to sleep 
• Maintaining a consistent bedtime and wake-up times on a daily basis 
• Avoiding alcohol or caffeine late in the afternoon or evening
• Limiting the use of electronic devices, including cell phones and tablets, for at least 30 mins or longer, before bed. 
• Setting up a personalised stable routine to execute every night to prepare for bed. 
• Relaxation techniques, such as reading a book, meditation, or calm music, in order to relieve stress. 
• An inviting, darker and quieter bedroom environment with a comfortable mattress and bedding. 
• If you are struggling to follow all of the above methods long-term or the techniques fail to significantly reduce your tendency to sleep procrastinate, it is recommended to consult a doctor who can assess your sleep habits, determine if you have a sleep disorder, and generate a plan to improve your sleep hygiene.