Circadian rhythm sleep disorder

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Circadian rhythm sleep disorder
Other namesCircadian rhythm sleep-wake disorders
Specialty Psychiatry, neurology, chronobiology

Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep-wake disorders (CRSWD), are a family of sleep disorders which affect the timing of sleep. CRSDs arise from a persistent pattern of sleep/wake disturbances that can be caused either by dysfunction in one's biological clock system, or by misalignment between one's endogenous oscillator and externally imposed cues. As a result of this mismatch, those affected by circadian rhythm sleep disorders have a tendency to fall asleep at unconventional time points in the day. These occurrences often lead to recurring instances of disturbed rest, where individuals affected by the disorder are unable to go to sleep and awaken at "normal" times for work, school, and other social obligations. Delayed sleep phase disorder, advanced sleep phase disorder, non-24-hour sleep–wake disorder and irregular sleep–wake rhythm disorder represents the four main types of CRSD. [1]

Contents

Overview

Humans, like most living organisms, have various biological rhythms. These biological clocks control processes that fluctuate daily (e.g., body temperature, alertness, hormone secretion), generating circadian rhythms. Among these physiological characteristics, the sleep-wake propensity can also be considered one of the daily rhythms regulated by the biological clock system. Human's sleeping cycles are tightly regulated by a series of circadian processes working in tandem, allowing for the experience of moments of consolidated sleep during the night and a long wakeful moment during the day. Conversely, disruptions to these processes and the communication pathways between them can lead to problems in sleeping patterns, which are collectively referred to as circadian rhythm sleep disorders.

Normal rhythm

A circadian rhythm is an entrainable, endogenous, biological activity that has a period of roughly twenty-four hours. This internal time-keeping mechanism is centralized in the suprachiasmatic nucleus (SCN) of humans, and allows for the internal physiological mechanisms underlying sleep and alertness to become synchronized to external environmental cues, like the light-dark cycle. [2] The SCN also sends signals to peripheral clocks in other organs, like the liver, to control processes such as glucose metabolism. [3] Although these rhythms will persist in constant light or dark conditions, different Zeitgebers (time givers such as the light-dark cycle) give context to the clock and allow it to entrain and regulate expression of physiological processes to adjust to the changing environment. Genes that help control light-induced entrainment include positive regulators BMAL1 and CLOCK and negative regulators PER1 and CRY. [4] A full circadian cycle can be described as a twenty-four hour circadian day, where circadian time zero (CT 0) marks the beginning of a subjective day for an organism and CT 12 marks the start of subjective night. [5]

Humans with regular circadian function have been shown to maintain regular sleep schedules, regulate daily rhythms in hormone secretion, and sustain oscillations in core body temperature. [6] Even in the absence of Zeitgebers, humans will continue to maintain a roughly 24-hour rhythm in these biological activities. Regarding sleep, normal circadian function allows people to maintain balance rest and wakefulness that allows people to work and maintain alertness during the day's activities, and rest at night. [7]

Some misconceptions regarding circadian rhythms and sleep commonly mislabel irregular sleep as a circadian rhythm sleep disorder. In order to be diagnosed with CRSD, there must be either a misalignment between the timing of the circadian oscillator and the surrounding environment, or failure in the clock entrainment pathway. [8] Among people with typical circadian clock function, there is variation in chronotypes, or preferred wake and sleep times, of individuals. Although chronotype varies from individual to individual, as determined by rhythmic expression of clock genes, people with typical circadian clock function will be able to entrain to environmental cues. For example, if a person wishes to shift the onset of a biological activity, like waking time, light exposure during the late subjective night or early subjective morning can help advance one's circadian cycle earlier in the day, leading to an earlier wake time. [9]

Diagnosis

The International Classification of Sleep Disorders classifies Circadian Rhythm Sleep Disorder as a type of sleep dyssomnia. Although studies suggest that 3% of the adult population has a CRSD, many people are often misdiagnosed with insomnia instead of a CRSD. Of adults diagnosed with sleep disorders, an estimated 10% have a CRSD and of adolescents with sleep disorders, an estimated 16% may have a CRSD. [10] Patients diagnosed with circadian rhythm sleep disorders typically express a pattern of disturbed sleep, whether that be excessive sleep that intrudes on working schedules and daily functions, or insomnia at desired times of sleep. Note that having a preference for extreme early or late wake times is not related to a circadian rhythm sleep disorder diagnosis. There must be distinct impairment of biological rhythms that affects the person's desired work and daily behavior. For a CRSD diagnosis, a sleep specialist gathers the history of a patient's sleep and wake habits, body temperature patterns, and dim-light melatonin onset (DLMO). [10] Gathering this data gives insight into the patient's current schedule, as well as the physiological phase markers of the patient's biological clock. [11]

The start of the CRSD diagnostic process is a thorough sleep history assessment. A standard questionnaire is used to record the sleep habits of the patient, including typical bedtime, sleep duration, sleep latency, and instances of waking up. The professional will further inquire about other external factors that may impact sleep. Prescription drugs that treat mood disorders like tricyclic antidepressants, selective serotonin reuptake inhibitors and other antidepressants are associated with abnormal sleep behaviors. Other daily habits like work schedule and timing of exercise are also recorded—because they may impact an individual's sleep and wake patterns. To measure sleep variables candidly, patients wear actigraphy watches that record sleep onset, wake time, and many other physiological variables. Patients are similarly asked to self-report their sleep habits with a week-long sleep diary to document when they go to bed, when they wake up, etc. to supplement the actigraphy data. Collecting this data allows sleep professionals to carefully document and measure patient's sleep habits and confirm patterns described in their sleep history. [10]

Other additional ways to classify the nature of a patient's sleep and biological clock are the morningness-eveningness questionnaire (MEQ) and the Munich ChronoType Questionnaire, both of which have fairly strong correlations with accurately reporting phase advanced or delayed sleep. [9] Questionnaires like the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) help gauge the severity of sleep disruption. Specifically, these questionnaires can help the professional assess the patient's problems with sleep latency, undesired early-morning wakefulness, and problems with falling or staying asleep. [10] Tayside children's sleep questionnaire is a ten-item questionnaire for sleep disorders in children aged between one and five years old. [12] [13] [14]

Types

CRSD Types.jpg

Currently, the International Classification of Sleep Disorders (ICSD-3) lists 6 disorders under the category of circadian rhythm sleep disorders. [15]

CRSDs can be categorized into two groups based on their underlying mechanisms: The first category is composed of disorders where the endogenous oscillator has been altered, known as intrinsic type disorders. The second category consists of disorders in which the external environment and the endogenous circadian clock are misaligned, called extrinsic type CRSDs. [16]

Intrinsic

Extrinsic

Alzheimer's disease

CRSD has been frequently associated with excessive daytime sleepiness and nighttime insomnia in patients diagnosed with Alzheimer's disease (AD), representing a common characteristic among AD patients as well as a risk factor of progressive functional impairments. [21] [22] [23] On one hand, it has been stated that people with AD have melatonin alteration and high irregularity in their circadian rhythm that lead to a disrupted sleep-wake cycle, probably due to damage on hypothalamic SCN regions typically observed in AD. [22] [23] On the other hand, disturbed sleep and wakefulness states have been related to worsening of an AD patient's cognitive abilities, emotional state and quality of life. [21] [22] [23] Moreover, the abnormal behavioural symptoms of the disease negatively contribute to overwhelming patient's relatives and caregivers as well. [21] [22]

However, the impact of sleep-wake disturbances on the subjective experience of a person with AD is not yet fully understood. [22] Therefore, further studies exploring this field have been highly recommended, mainly considering the increasing life expectancy and significance of neurodegenerative diseases in clinical practices. [23]

Treatment

Possible treatments for circadian rhythm sleep disorders include:

See also

Related Research Articles

Free-running sleep is a rare sleep pattern whereby the sleep schedule of a person shifts later every day. It occurs as the sleep disorder non-24-hour sleep–wake disorder or artificially as part of experiments used in the study of circadian and other rhythms in biology. Study subjects are shielded from all time cues, often by a constant light protocol, by a constant dark protocol or by the use of light/dark conditions to which the organism cannot entrain such as the ultrashort protocol of one hour dark and two hours light. Also, limited amounts of food may be made available at short intervals so as to avoid entrainment to mealtimes. Subjects are thus forced to live by their internal circadian "clocks".

Jet lag is a physiological condition that results from alterations to the body's circadian rhythms caused by rapid long-distance trans-meridian travel. For example, someone flying from New York to London, i.e. from west to east, feels as if the time were five hours earlier than local time, and someone travelling from London to New York, i.e. from east to west, feels as if the time were five hours later than local time. The phase shift when traveling from east to west is referred to as phase-delay of the circadian circle, whereas going west to east is phase-advance of the circadian circle. Most travelers find that it is harder to time zone adjust when traveling to the east. Jet lag was previously classified as one of the circadian rhythm sleep disorders.

<span class="mw-page-title-main">Circadian rhythm</span> Natural internal process that regulates the sleep-wake cycle

A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximise the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.

<span class="mw-page-title-main">Delayed sleep phase disorder</span> Chronic mismatch between a persons normal daily rhythm, compared to other people and societal norms

Delayed sleep phase disorder (DSPD), more often known as delayed sleep phase syndrome and also as delayed sleep–wake phase disorder, is the delaying of a person's circadian rhythm compared to those of societal norms. The disorder affects the timing of biological rhythms including sleep, peak period of alertness, core body temperature, and hormonal cycles.

Advanced Sleep Phase Disorder (ASPD), also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder, is a condition that is characterized by a recurrent pattern of early evening sleepiness and very early morning awakening. This sleep phase advancement can interfere with daily social and work schedules, and results in shortened sleep duration and excessive daytime sleepiness. The timing of sleep and melatonin levels are regulated by the body's central circadian clock, which is located in the suprachiasmatic nucleus in the hypothalamus.

Somnolence is a state of strong desire for sleep, or sleeping for unusually long periods. It has distinct meanings and causes. It can refer to the usual state preceding falling asleep, the condition of being in a drowsy state due to circadian rhythm disorders, or a symptom of other health problems. It can be accompanied by lethargy, weakness and lack of mental agility.

In chronotherapy, an attempt is made to move bedtime and rising time later and later each day, around the clock, until a person is sleeping on a normal schedule. This treatment can be used by people with delayed sleep phase disorder (DSPD), who generally cannot reset their circadian rhythm by moving their bedtime and rising time earlier. DSPD is a circadian rhythm sleep disorder, characterised by a mismatch between a person's internal biological clock and societal norms. Chronotherapy uses the human phase response to light or melatonin. The American Academy of Sleep Medicine has recommended chronotherapy for the treatment of circadian rhythm and sleep disorders.

Non-24-hour sleep–wake disorder is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society". Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blind, it can also affect sighted people. Non-24 may also be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) has provided CRSD guidelines since 2007 with the latest update released in 2015.

A phase response curve (PRC) illustrates the transient change in the cycle period of an oscillation induced by a perturbation as a function of the phase at which it is received. PRCs are used in various fields; examples of biological oscillations are the heartbeat, circadian rhythms, and the regular, repetitive firing observed in some neurons in the absence of noise.

Shift work sleep disorder (SWSD) is a circadian rhythm sleep disorder characterized by insomnia, excessive sleepiness, or both affecting people whose work hours overlap with the typical sleep period. Insomnia can be the difficulty to fall asleep or to wake up before the individual has slept enough. About 20% of the working population participates in shift work. SWSD commonly goes undiagnosed, so it's estimated that 10–40% of shift workers have SWSD. The excessive sleepiness appears when the individual has to be productive, awake and alert. Both symptoms are predominant in SWSD. There are numerous shift work schedules, and they may be permanent, intermittent, or rotating; consequently, the manifestations of SWSD are quite variable. Most people with different schedules than the ordinary one might have these symptoms but the difference is that SWSD is continual, long-term, and starts to interfere with the individual's life.

In the study of chronobiology, entrainment occurs when rhythmic physiological or behavioral events match their period to that of an environmental oscillation. It is ultimately the interaction between circadian rhythms and the environment. A central example is the entrainment of circadian rhythms to the daily light–dark cycle, which ultimately is determined by the Earth's rotation. Exposure to certain environmental stimuli will cue a phase shift, and abrupt change in the timing of the rhythm. Entrainment helps organisms maintain an adaptive phase relationship with the environment as well as prevent drifting of a free running rhythm. This stable phase relationship achieved is thought to be the main function of entrainment.

A chronotype is the behavioral manifestation of underlying circadian rhythm's myriad of physical processes. A person's chronotype is the propensity for the individual to sleep at a particular time during a 24-hour period. Eveningness and morningness are the two extremes with most individuals having some flexibility in the timing of their sleep period. However, across development there are changes in the propensity of the sleep period with pre-pubescent children preferring an advanced sleep period, adolescents preferring a delayed sleep period and many elderly preferring an advanced sleep period.

Light effects on circadian rhythm are the effects that light has on circadian rhythm.

Irregular sleep–wake rhythm disorder (ISWRD) is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode, and irregularity from day to day. Affected individuals have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake. The total time asleep per 24 hours is normal for the person's age. The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated.

Michael Terman is an American psychologist best known for his work in applying the biological principles of the circadian timing system to psychiatric treatments for depression and sleep disorders. This subspecialty is known as Chronotherapeutics.

Familial sleep traits are heritable variations in sleep patterns, resulting in abnormal sleep-wake times and/or abnormal sleep length.

Dr. Debra J. Skene is a chronobiologist with specific interest in the mammalian circadian rhythm and the consequences of disturbing the circadian system. She is also interested in finding their potential treatments for people who suffer from circadian misalignment. Skene and her team of researchers tackle these questions using animal models, clinical trials, and most recently, liquid chromatography-mass spectrometry. Most notably, Skene is credited for her evidence of a novel photopigment in humans, later discovered to be melanopsin. She was also involved in discovering links between human PER3 genotype and an extremely shifted sleep schedules categorized as extreme diurnal preference. Skene received her Bachelor of Pharmacy, Master of Science, and Ph.D. in South Africa.

<span class="mw-page-title-main">Charmane Eastman</span> American academic research scientist in chronobiology

Charmane Eastman is an American academic research scientist whose career has focused on studying circadian rhythms and their relationships to sleep, jet lag, and shift work. She has also studied winter depression, more properly known as seasonal affective disorder (SAD). Of special focus are the effects of bright light and melatonin on circadian rhythms.

In chronobiology, photoentrainment refers to the process by which an organism's biological clock, or circadian rhythm, synchronizes to daily cycles of light and dark in the environment. The mechanisms of photoentrainment differ from organism to organism. Photoentrainment plays a major role in maintaining proper timing of physiological processes and coordinating behavior within the natural environment. Studying organisms’ different photoentrainment mechanisms sheds light on how organisms may adapt to anthropogenic changes to the environment.

Elizabeth Klerman is a Professor of Neurology at Harvard Medical School whose research focuses on applying circadian and sleep research principles to human physiology and pathophysiology. She also uses mathematical analysis and modeling to study human circadian, sleep, and objective neurobehavioral performance and subjective (self-reported) mood and alertness rhythms.

References

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