Misplaced Pages

#526473

92-522: Circadian rhythm sleep disorders ( CRSD ), also known as circadian rhythm sleep–wake disorders ( CRSWD ), are a family of sleep disorders that affect the timing of sleep. CRSDs cause a persistent pattern of sleep/wake disturbances that arise 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 misalignment, those affected by circadian rhythm sleep disorders can fall asleep at unconventional time points in

184-1060: A polymorphism in Clock , rs6832769, may be related to the personality trait agreeableness . Another single nucleotide polymorphism (SNP) in Clock , 3111C, associated with diurnal preference, is also associated with increased insomnia , difficulty losing weight, and recurrence of major depressive episodes in patients with bipolar disorder . In mice, Clock has been implicated in sleep disorders , metabolism , pregnancy , and mood disorders . Clock mutant mice sleep less than normal mice each day. The mice also display altered levels of plasma glucose and rhythms in food intake. These mutants develop metabolic syndrome symptoms over time. Furthermore, Clock mutants demonstrate disrupted estrous cycles and increased rates of full-term pregnancy failure. Mutant Clock has also been linked to bipolar disorder-like symptoms in mice, including mania and euphoria . Clock mutant mice also exhibit increased excitability of dopamine neurons in reward centers of

276-754: A better understanding and offer possibilities to improve targeting of at-risk populations—and the implementation of treatments to curb the cognitive decline of AD patients. In individuals with psychiatric illnesses sleep disorders may include a variety of clinical symptoms, including but not limited to: excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, nightmares, sleep talking, sleepwalking, and poor sleep quality. Sleep disturbances - insomnia, hypersomnia and delayed sleep-phase disorder - are quite prevalent in severe mental illnesses such as psychotic disorders. In those with schizophrenia , sleep disorders contribute to cognitive deficits in learning and memory. Sleep disturbances often occur before

368-528: A central role as a transcription factor in the circadian pacemaker. In Drosophila , newly synthesized CLOCK (CLK) is hypophosphorylated in the cytoplasm before entering the nucleus. Once in the nuclei, CLK is localized in nuclear foci and is later redistributed homogeneously. CYCLE (CYC) (also known as dBMAL for the BMAL1 ortholog in mammals) dimerizes with CLK via their respective PAS domains . This dimer then recruits co-activator CREB-binding protein (CBP) and

460-592: 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. 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

552-469: A disrupted sleep–wake cycle, probably due to damage on hypothalamic SCN regions typically observed in AD. 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. Moreover, the abnormal behavioural symptoms of the disease negatively contribute to overwhelming patients' relatives and caregivers as well. However,

644-469: A growing resemblance between some sleep stages (N1 and N2). More than 65% of people with Alzheimer's disease have this type of sleep disturbance. One factor that could explain this change in sleep architecture is a change in circadian rhythm, which regulates sleep. A disruption of the circadian rhythm would generate sleep disturbances. Some studies show that people with AD have a delayed circadian rhythm, whereas in normal aging, an advanced circadian rhythm

736-462: A hereditary component. A total of 632 participants, half with iRBD and half without, completed self-report questionnaires. The results of the study suggest that people with iRBD are more likely to report having a first-degree relative with the same sleep disorder than people of the same age and sex that do not have the disorder. More research needs to be conducted to further understand the hereditary nature of sleep disorders. A population susceptible to

828-977: A necessary diagnostic criterion—but one of the most frequent symptoms of individuals with major depressive disorder (MDD). Among individuals with MDD, insomnia and hypersomnia have prevalence estimates of 88% and 27%, respectively, whereas individuals with insomnia have a threefold increased risk of developing MDD. Depressed mood and sleep efficiency strongly co-vary, and while sleep regulation problems may precede depressive episodes, such depressive episodes may also precipitate sleep deprivation. Fatigue, as well as sleep disturbances such as irregular and excessive sleepiness, are linked to symptoms of depression. Recent research has even pointed to sleep problems and fatigues as potential driving forces bridging MDD symptoms to those of co-occurring generalized anxiety disorder. Treatments for sleep disorders generally can be grouped into four categories: None of these general approaches are sufficient for all patients with sleep disorders. Rather,

920-413: 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. The International Classification of Sleep Disorders classifies Circadian Rhythm Sleep Disorder as a type of sleep dyssomnia . Although studies suggest that 3% of

1012-560: A positive feedback relationship. As a result, sleep disturbances are no longer only a symptom of AD; the relationship between sleep disturbances and AD is bidirectional. At the same time, it has been shown that memory consolidation in long-term memory (which depends on the hippocampus) occurs during NREM sleep. This indicates that a decrease in the NREM sleep will result in less consolidation, resulting in poorer memory performances in hippocampal-dependent long-term memory. This drop in performance

SECTION 10

#1733085295527

1104-490: A positive limb of a feedback loop. The binding of CLOCK-BMAL to an E-box promoter element activates transcription of clock genes such as per 1, 2, and 3 and tim in mice. It has been shown in mice that CLOCK-BMAL also activates the Nicotinamide phosphoribosyltransferase gene (also called Nampt ), part of a separate feedback loop. This feedback loop creates a metabolic oscillator. The CLOCK-BMAL dimer activates transcription of

1196-432: 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). Gathering this data gives insight into

1288-429: A scored questionnaire. This region is well conserved between mice and humans and polymorphisms have been shown to affect mRNA stability, indicating allelic variants could disrupt normal circadian patterns in mammals leading to conditions such as insomnia or other sleep disorders. Clock mutant organisms can either possess a null mutation or an antimorphic allele at the Clock locus that codes for an antagonist to

1380-505: A self-sustaining clock via gene duplication and functional divergence of clock genes. The kaiA / B / C gene clusters remain the oldest of the clock genes as they are present in cyanobacteria , with kai C most likely the ancestor of kai A and kaiB. The function of these ancestral clock genes was most likely related to chromosome function before evolving a timing mechanism. The kai A and kai B genes arose after cyanobacteria separated from other prokaryotes. Harsh climate conditions in

1472-437: 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. ipRGCs (intrinsically photosensitive Retinal Ganglion Cells ), for example, are involved in modulating the circadian rhythm because of the expression of melanopsin, which absorbs light in the blue part (around 480 nm). Conversely, disruptions to these processes and

1564-422: 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. Other additional ways to classify the nature of a patient's sleep and biological clock are the morningness-eveningness questionnaire (MEQ) and

1656-681: Is a gene encoding a basic helix-loop-helix - PAS transcription factor that is known to affect both the persistence and period of circadian rhythms . Research shows that the CLOCK gene plays a major role as an activator of downstream elements in the pathway critical to the generation of circadian rhythms . The CLOCK gene was first identified in 1997 by Joseph Takahashi and his colleagues. Takahashi used forward mutagenesis screening of mice treated with N-ethyl-N-nitrosourea to create and identify mutations in key genes that broadly affect circadian activity. The CLOCK mutants discovered through

1748-576: Is a ten-item questionnaire for sleep disorders in children aged between one and five years old. Currently, the International Classification of Sleep Disorders (ICSD-3) lists 6 disorders under the category of circadian rhythm sleep disorders. 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

1840-527: Is also common among adolescents, whose school schedules are often incompatible with their natural circadian rhythm. Effective treatment begins with careful diagnosis using sleep diaries and perhaps sleep studies. Modifications in sleep hygiene may resolve the problem, but medical treatment is often warranted. Special equipment may be required for treatment of several disorders such as obstructive apnea, circadian rhythm disorders and bruxism. In severe cases, it may be necessary for individuals to accept living with

1932-550: Is further phosphorylated. Once phosphorylated, this CLK-CYC complex binds to the E-box elements of the promoters of period (per) and timeless (tim) via its bHLH domain, causing the stimulation of gene expression of per and tim . A large molar excess of period (PER) and timeless (TIM) proteins causes formation of the PER-TIM heterodimer which prevents the CLK-CYC heterodimer from binding to

SECTION 20

#1733085295527

2024-663: Is generally studied in adults, rather than children. Further research would be needed to study the effects of acupuncture on sleep disorders in children. Research suggests that hypnosis may be helpful in alleviating some types and manifestations of sleep disorders in some patients. "Acute and chronic insomnia often respond to relaxation and hypnotherapy approaches, along with sleep hygiene instructions." Hypnotherapy has also helped with nightmares and sleep terrors. There are several reports of successful use of hypnotherapy for parasomnias specifically for head and body rocking, bedwetting and sleepwalking. Hypnotherapy has been studied in

2116-449: Is insomnia, in addition to hypersomnia, nightmares, poor sleep quality, OSA, extreme daytime sleepiness, etc. Moreover, animal models have shown that sleep debt can induce episodes of bipolar mania in laboratory mice, but these models are still limited in their potential to explain bipolar disease in humans with all its multifaceted symptoms, including those related to sleep disturbances. Sleep disturbances (insomnia or hypersomnia) are not

2208-453: Is necessary for normal circadian function. Furthermore, it suggested that the CLOCK-BMAL1 dimer need not exist to modulate other elements of the circadian pathway. Neuronal PAS domain containing protein 2 ( NPAS2 , a CLOCK paralog ) can substitute for CLOCK in these Clock -null mice. Mice with one NPAS2 allele showed shorter periods at first, but eventual arrhythmic behavior. In humans,

2300-566: Is necessary to rescue circadian rhythms in Clock mutants. The CLOCK-BMAL dimer is involved in regulation of other genes and feedback loops. An enzyme SIRT1 also binds to the CLOCK-BMAL complex and acts to suppress its activity, perhaps by deacetylation of Bmal1 and surrounding histones . However, SIRT1's role is still controversial and it may also have a role in deacetylating PER protein, targeting it for degradation. The CLOCK-BMAL dimer acts as

2392-787: Is one of the central symptoms of AD. Recent studies have also linked sleep disturbances, neurogenesis and AD. The subgranular zone and the subventricular zone continued to produce new neurons in adult brains. These new cells are then incorporated into neuronal circuits and the subgranular zone, which is found in the hippocampus. These new cells contribute to learning and memory, playing an essential role in hippocampal-dependent memory. However, recent studies have shown that several factors can interrupt neurogenesis, including stress and prolonged sleep deprivation (more than one day). The sleep disturbances encountered in AD could therefore suppress neurogenesis—and thus impair hippocampal functions. This would contribute to diminished memory performances and

2484-414: Is present. In addition to these psychological symptoms, at a neurological level there are two main symptoms of Alzheimer's disease. The first is an accumulation of beta-amyloid waste forming aggregate "plaques". The second is an accumulation of tau protein. It has been shown that the sleep-wake cycle acts on the beta-amyloid burden, which is a central component found in AD. As individuals awaken,

2576-682: Is recognized by the American Academy of Sleep Medicine (AASM), and these dentists are organized in the Academy of Dental Sleep Medicine (USA). Occupational therapy is an area of medicine that can also address a diagnosis of sleep disorder, as rest and sleep is listed in the Occupational Therapy Practice Framework (OTPF) as its own occupation of daily living. Rest and sleep are described as restorative in order to support engagement in other occupational therapy occupations. In

2668-486: Is responsible for this through the phenomenon of glymphatic clearance. Thus, during wakefulness, the AB burden is greater because the metabolic activity and oxidative stress are higher, and there is no protein degradation by the glymphatic clearance. During sleep, the burden is reduced as there is less metabolic activity and oxidative stress (in addition to the glymphatic clearance that occurs). Glymphatic clearance occurs during

2760-710: Is sometimes absent), spindles and the length of time spent in REM sleep are also reduced, while its latency increases. Poor sleep onset in AD has been associated with dream-related hallucination, increased restlessness, wandering and agitation that seem related to sundowning - a typical chronobiological phenomenon presented in the disease. In Alzheimer's disease, in addition to cognitive decline and memory impairment, there are also significant sleep disturbances with modified sleep architecture. The latter may consist in sleep fragmentation, reduced sleep duration, insomnia, increased daytime napping, decreased quantity of some sleep stages, and

2852-416: Is useful in helping people fall asleep faster (decreased sleep latency ), stay asleep longer, and experience improved sleep quality. To test this, a study was conducted that compared subjects who had taken melatonin to subjects with primary sleep disorders who had taken a placebo. Researchers assessed sleep onset latency, total minutes slept, and overall sleep quality in the melatonin and placebo groups to note

Circadian rhythm sleep disorder - Misplaced Pages Continue

2944-687: The American Board of Sleep Medicine . Those passing the Sleep Medicine Specialty Exam received the designation "diplomate of the ABSM ". Sleep medicine is now a recognized subspecialty within internal medicine , family medicine , pediatrics , otolaryngology , psychiatry and neurology in the United States . Certification in Sleep medicine shows that the specialist: has demonstrated expertise in

3036-733: The Munich ChronoType Questionnaire , both of which have fairly strong correlations with accurately reporting phase advanced or delayed sleep. 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. Tayside children's sleep questionnaire

3128-527: The Nampt gene, which codes for the NAMPT protein. NAMPT is part of a series of enzymatic reactions that covert niacin (also called nicotinamide ) to NAD . SIRT1, which requires NAD for its enzymatic activity, then uses increased NAD levels to suppress BMAL1 through deacetylation. This suppression results in less transcription of the NAMPT, less NAMPT protein, less NAD made, and therefore less SIRT1 and less suppression of

3220-559: The epigenetics of the Clock gene may lead to an increased risk of breast cancer . It was found that in women with breast cancer, there was significantly less methylation of the Clock promoter region. It was also noted that this effect was greater in women with estrogen and progesterone receptor-negative tumors. The CLOCK gene may also be a target for somatic mutations in microsatellite unstable colorectal cancers . In one study, 53% of microsatellite instability colorectal cancer cases contained somatic CLOCK mutations. Nascent research in

3312-457: The insect-vertebrate split roughly 500 mya. WC1, an analog of CLOCK/BMAL1 found in fungal genomes, is a proposed candidate common ancestor predating the fungi-animal split . A BLAST search conducted in a 2004 review of clock gene evolution suggested the Clock gene may have arisen from a duplication in the BMAL1 gene, though this hypothesis remains speculative. Another theory alternatively proposes

3404-501: The 70s and 80s, the medical importance of sleep was recognized. By the 1970s in the US, clinics and laboratories devoted to the study of sleep and sleep disorders had been founded, and a need for standards arose. The medical community began paying more attention to primary sleep disorders, such as sleep apnea, as well as the role and quality of sleep in other conditions. Specialists in sleep medicine were originally and continue to be certified by

3496-458: The CLOCK protein. This mutation causes dominant effects: half of the heterozygous flies with this mutant gene have a lengthened period of 24.8 hours, while the other half become arrhythmic. Homozygous flies lose their circadian rhythm. Furthermore, the same researchers demonstrated that these mutant flies express low levels of PER and TIM proteins, indicating that Clock functions as a positive element in

3588-506: The CLOCK-BMAL dimer. This dimer can again positively activate the Nampt gene transcription and the cycle continues, creating another oscillatory loop involving CLOCK-BMAL as positive elements. The key role that Clock plays in metabolic and circadian loops highlights the close relationship between metabolism and circadian clocks. The first circadian rhythms were most likely generated by light-driven cell division cycles in ancestral prokaryotic species. This proto-rhythm later evolved into

3680-611: The E-box regulatory elements. PER and CRY proteins accumulate and dimerize during subjective night, and translocate into the nucleus to interact with the CLOCK:BMAL1 complex, directly inhibiting their own expression. This research has been conducted and validated through crystallographic analysis. CLOCK exhibits histone acetyl transferase (HAT) activity, which is enhanced by dimerization with BMAL1. Dr. Paolo Sassone-Corsi and colleagues demonstrated in vitro that CLOCK mediated HAT activity

3772-566: The E-boxes of per and tim , essentially blocking per and tim transcription. CLK is hyperphosphorylated when doubletime (DBT) kinase interacts with the CLK-CYC complex in a PER reliant manner, destabilizing both CLK and PER, leading to the degradation of both proteins. Hypophosphorylated CLK then accumulates, binds to the E-boxes of per and tim and activates their transcription once again. This cycle of post-translational phosphorylation suggest that temporal phosphorylation of CLK helps in

Circadian rhythm sleep disorder - Misplaced Pages Continue

3864-702: The NPAS2 gene as the paralog of CLOCK that performs a similar role in the circadian rhythm pathway but in different tissues. Allelic variations within the Clock1a gene in particular are hypothesized to have effects on seasonal timing according to a 2014 study conducted in a population of cyprinid fishes. Polymorphisms in the gene mainly affect the length of the PolyQ domain region, providing an example of divergent evolution where species sharing an ecological niche will partition resources in seasonally variable environments. The length of

3956-458: The NREM SWS sleep. This sleep stage decreases in normal aging, resulting in less glymphatic clearance and increased AB burden that will form AB plaques. Therefore, sleep disturbances in individuals with AD will amplify this phenomenon. The decrease in the quantity and quality of the NREM SWS, as well as the disturbances of sleep will therefore increase the AB plaques. This initially occurs in

4048-853: The OTPF, the occupation of rest and sleep is broken down into rest, sleep preparation, and sleep participation. Occupational therapists have been shown to help improve restorative sleep through the use of assistive devices/equipment, cognitive behavioral therapy for Insomnia , therapeutic activities, and lifestyle interventions. In the UK, knowledge of sleep medicine and possibilities for diagnosis and treatment seem to lag. The Imperial College Healthcare shows attention to obstructive sleep apnea syndrome (OSA) and very few other sleep disorders. Some NHS trusts have specialist clinics for respiratory and neurological sleep medicine. According to one meta-analysis of sleep disorders in children, confusional arousals and sleepwalking are

4140-460: The PD population), hypersomnia (more than 50% of the PD population), and REM sleep behavior disorder (RBD) - that may affect around 40% of the PD population and it is associated with increased motor symptoms. Furthermore, RBD has been highlighted as a strong precursor for future development of those neurodegenerative diseases over several years in prior, which seems to be a great opportunity for improving

4232-644: The PolyQ domain is associated with changes in transcription level of CLOCK. On average, longer allele lengths were correlated with recently derived species and earlier-spawning species, most likely due to seasonal changes in water temperature. The researchers hypothesize that the length of the domain may serve to compensate for changes in temperature by altering the rate of CLOCK transcription. All other amino acids remained identical across native species, indicating that functional constraint may be another factor influencing CLOCK gene evolution in addition to gene duplication and diversification . One 2017 study investigating

4324-409: 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. Some misconceptions regarding circadian rhythms and sleep commonly mislabel irregular sleep as

4416-447: The absence of volitional sleep deprivation , "is almost inevitably caused by an identifiable and treatable sleep disorder", such as sleep apnea, narcolepsy , idiopathic hypersomnia , Kleine–Levin syndrome , menstrual-related hypersomnia, idiopathic recurrent stupor, or circadian rhythm disturbances . Another common complaint is insomnia, a set of symptoms which can have a great many different causes, physical and mental. Management in

4508-497: 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. 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

4600-403: The allele become arrhythmic. In both heterozygotes and homozygotes, this mutation also produces lengthened periods and arrhythmicity at the single-cell level. Clock -/- null mutant mice, in which Clock has been knocked out, display completely normal circadian rhythms. The discovery of a null Clock mutant with a wild-type phenotype directly challenged the widely accepted premise that Clock

4692-566: The amplitude of circadian rhythms. The mouse homolog to the Jrk mutant is the ClockΔ19 mutant that possesses a deletion in exon 19 of the Clock gene. This dominant-negative mutation results in a defective CLOCK-BMAL dimer, which causes mice to have a decreased ability to activate per transcription. In constant darkness, ClockΔ19 mice heterozygous for the Clock mutant allele exhibit lengthened circadian periods, while ClockΔ19/Δ19 mice homozygous for

SECTION 50

#1733085295527

4784-442: The brain. These results have led Colleen McClung to propose using Clock mutant mice as a model for human mood and behavior disorders. The CLOCK-BMAL dimer has also been shown to activate reverse-erb receptor alpha ( Rev-ErbA alpha ) and retinoic acid orphan receptor alpha ( ROR-alpha ). REV-ERBα and RORα regulate Bmal by binding to retinoic acid-related orphan receptor response elements (ROREs) in its promoter. Variations in

4876-588: The changing environment. Genes that help control light-induced entrainment include positive regulators BMAL1 and CLOCK and negative regulators PER1 and CRY . 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. 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. Even in

4968-443: The choice of a specific treatment depends on the patient's diagnosis, medical and psychiatric history, and preferences, as well as the expertise of the treating clinician. Often, behavioral/psychotherapeutic and pharmacological approaches may be compatible, and can effectively be combined to maximize therapeutic benefits. Management of sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on

5060-472: The circadian loop. While the mutation affects the circadian clock of the fly, it does not cause any physiological or behavioral defects. The similar sequence between Jrk and its mouse homolog suggests common circadian rhythm components were present in both Drosophila and mice ancestors. A recessive allele of Clock leads to behavioral arrhythmicity while maintaining detectable molecular and transcriptional oscillations. This suggests that Clk contributes to

5152-522: The communication pathways between them can lead to problems in sleeping patterns, which are collectively referred to as circadian rhythm sleep disorders. 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

5244-455: The day, or experience excessive daytime sleepiness if they resist. These occurrences often lead to recurring instances of disrupted rest and wakefulness, 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

5336-505: The degree of impairment is related to the severity of those symptoms. Treatment of allergies has also been shown to help sleep apnea. A review of the evidence in 2012 concluded that current research is not rigorous enough to make recommendations around the use of acupuncture for insomnia . The pooled results of two trials on acupuncture showed a moderate likelihood that there may be some improvement to sleep quality for individuals with insomnia. This form of treatment for sleep disorders

5428-824: The development of sleep disorders includes people who have experienced a traumatic brain injury (TBI) . Because many researchers have focused on this issue, a systematic review was conducted to synthesize their findings. The results indicate that individuals who experienced a TBI are most disproportionately at risk for developing narcolepsy, obstructive sleep apnea, excessive daytime sleepiness, and insomnia. Neurodegenerative diseases have often been associated with sleep disorders, mainly when they are characterized by abnormal accumulation of alpha-synuclein , such as multiple system atrophy (MSA), Parkinson's disease (PD) and Lewy body disease (LBD). For instance, people diagnosed with PD have often presented different kinds of sleep concerns, commonly in regard to insomnia (around 70% of

5520-520: The diagnosis and management of clinical conditions that occur during sleep, that disturb sleep, or that are affected by disturbances in the wake-sleep cycle. This specialist is skilled in the analysis and interpretation of comprehensive polysomnography, and well-versed in emerging research and management of a sleep laboratory. Competence in sleep medicine requires an understanding of a myriad of very diverse disorders. Many of which present with similar symptoms such as excessive daytime sleepiness, which, in

5612-399: The differences. In the end, researchers found that melatonin decreased sleep onset latency and increased total sleep time but had an insignificant and inconclusive impact on the quality of sleep compared to the placebo group. Due to rapidly increasing knowledge and understanding of sleep in the 20th century, including the discovery of REM sleep in the 1950s and circadian rhythm disorders in

SECTION 60

#1733085295527

5704-413: The disorder, however well managed. Some sleep disorders have been found to compromise glucose metabolism. Histamine plays a role in wakefulness in the brain. An allergic reaction over produces histamine, causing wakefulness and inhibiting sleep. Sleep problems are common in people with allergic rhinitis . A study from the N.I.H. found that sleep is dramatically impaired by allergic symptoms, and that

5796-687: The early history of the Earth’s formation, such as UV irradiation, may have led to the diversification of clock genes in prokaryotes in response to drastic changes in climate. Cryptochromes , light-sensitive proteins regulated by Cry genes , are most likely descendents of kaiC resulting from a genome duplication predating the Cambrian explosion and are responsible for negative regulation of circadian clocks. Other distinct clock gene lineages arose early in vertebrate evolution, with gene BMAL1 paralogous to CLOCK. Their common ancestor, however, most likely predated

5888-568: The elderly, the risk of developing sleep disordered breathing, periodic limb movements, restless legs syndrome , REM sleep behavior disorders, insomnia, and circadian rhythm disturbances is especially increased. A systematic review found that traumatic childhood experiences (such as family conflict or sexual trauma) significantly increases the risk for a number of sleep disorders in adulthood, including sleep apnea , narcolepsy , and insomnia . In addition, an evidence-based synopsis suggests that idiopathic REM sleep behavior disorder (iRBD) may have

5980-516: The external environment and the endogenous circadian clock are misaligned, called extrinsic type CRSDs. 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. On one hand, it has been stated that people with AD have melatonin alteration and high irregularity in their circadian rhythm that lead to

6072-431: The first part of an individual's sleep cycle, the first slow wave of sleep During the first slow wave of sleep period of the sleep cycle the mind and body slow down causing one to feel drowsy and relaxed. At this stage it is the easiest to wake up, therefore many children do not remember what happened during this time. Nightmares are also considered a parasomnia among children, who typically remember what took place during

6164-813: The form of overall time asleep, was observed. In order to assess sleep quality, researchers used subjective measures (i.e. questionnaires ) and objective measures (i.e. polysomnography ). The results of the study suggest that music therapy did improve sleep quality in subjects with acute or chronic sleep disorders, though only when tested subjectively. Although these results are not fully conclusive and more research should be conducted, it still provides evidence that music therapy can be an effective treatment for sleep disorders. In another study specifically looking to help people with insomnia, similar results were seen. The participants that listened to music experienced better sleep quality than those who did not listen to music. Listening to slower pace music before bed can help decrease

6256-458: The four main types of CRSD. 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. Humans' sleeping cycles are tightly regulated by

6348-445: The heart rate, making it easier to transition into sleep. Studies have indicated that music helps induce a state of relaxation that shifts an individual's internal clock towards the sleep cycle. This is said to have an effect on children and adults with various cases of sleep disorders. Music is most effective before bed once the brain has been conditioned to it, helping to achieve sleep much faster. Research suggests that melatonin

6440-408: The hippocampus, which is a brain structure integral in long-term memory formation. Hippocampus cell death occurs, which contributes to diminished memory performance and cognitive decline found in AD. Although the causal relationship is unclear, the development of AD correlates with the development of prominent sleep disorders. In the same way, sleep disorders exacerbate disease progression, forming

6532-527: The impact of sleep–wake disturbances on the subjective experience of a person with AD is not yet fully understood. Therefore, further studies exploring this field have been highly recommended, mainly considering the increasing life expectancy and significance of neurodegenerative diseases in clinical practices. Possible treatments for circadian rhythm sleep disorders include: Sleep disorders Sleep disorders are broadly classified into dyssomnias , parasomnias , circadian rhythm sleep disorders involving

6624-831: The increasing life expectancy calls for a deeper understanding of the relationship between sleep disorders and neurodegenerative disease. Sleep disturbances have been also observed in Alzheimer's disease (AD), affecting about 45% of its population. When based on caregiver reports, this percentage increases to about 70%. As well as in PD population, insomnia and hypersomnia are frequently recognized in AD patients, which have been associated with accumulation of beta-amyloid , circadian rhythm sleep disorders (CRSD) and melatonin alteration. Additionally, changes in sleep architecture are observed in AD. Although sleep architecture seems to naturally change with age, its development appears aggravated in AD patients. SWS potentially decreases (and

6716-405: The light-dark cycle. The SCN also sends signals to peripheral clocks in other organs, like the liver, to control processes such as glucose metabolism. 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

6808-485: The main behavioral symptoms of bipolar disorder is abnormal sleep. Studies have suggested that 23-78% of individuals with bipolar disorders consistently report symptoms of excessive time spent sleeping, or hypersomnia. The pathogenesis of bipolar disorder, including the higher risk of suicidal ideation, could possibly be linked to circadian rhythm variability, and sleep disturbances are a good predictor of mood swings. The most common sleep-related symptom of bipolar disorder

6900-675: The nightmare. However, nightmares only occur during the last stage of sleep - Rapid Eye Movement (REM) sleep. REM is the deepest stage of sleep, it is named for the host of neurological and physiological responses an individual can display during this period of the sleep cycle which are similar to being awake . Clock genes 4H10 9575 12753 ENSG00000134852 ENSMUSG00000029238 O15516 O08785 NM_001267843 NM_004898 NM_007715 NM_001289826 NM_001305222 NP_001254772 NP_004889 NP_001276755 NP_001292151 NP_031741 CLOCK ( backronym for circadian locomotor output cycles kaput )

6992-535: The onset of psychosis. Sleep deprivation can also produce hallucinations, delusions and depression. A 2019 study investigated the three above-mentioned sleep disturbances in schizophrenia-spectrum (SCZ) and bipolar (BP) disorders in 617 SCZ individuals, 440 BP individuals, and 173 healthy controls (HC). Sleep disturbances were identified using the Inventory for Depressive Symptoms - clinician rated scale (IDS-C). Results suggested that at least one type of sleep disturbance

7084-1046: The patient's current schedule, as well as the physiological phase markers of the patient's biological clock. 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

7176-499: The production of beta-amyloid protein will be more consistent than its production during sleep. This is explained by two phenomena. The first is that the metabolic activity will be higher during waking, thus resulting in greater secretion of beta-amyloid protein. The second is that oxidative stress will also increase, which leads to greater AB production. On the other hand, it is during sleep that beta-amyloid residues are degraded to prevent plaque formation. The glymphatic system

7268-443: The progression of AD, and the progression of AD would aggravate sleep disturbances. Changes in sleep architecture found in patients with AD occur during the preclinical phase of AD. These changes could be used to detect those most at risk of developing AD. However, this is still only theoretical. While the exact mechanisms and the causal relationship between sleep disturbances and AD remains unclear, these findings already provide

7360-410: The role of CLOCK expression in neurons determined its function in regulating transcriptional networks that could provide insight into human brain evolution. The researchers synthesized differentiated human neurons in vitro and then performed gene knockdown to test the effect of CLOCK on neuronal cell signaling. When CLOCK activity was disrupted, increased neuronal migration of tissue in the neocortex

7452-533: The screen displayed an abnormally long period of daily activity. This trait proved to be heritable . Mice bred to be heterozygous showed longer periods of 24.4 hours compared to the control 23.3 hour period. Mice homozygous for the mutation showed 27.3 hour periods, but eventually lost all circadian rhythmicity after several days in constant darkness. That showed that "intact CLOCK genes" are necessary for normal mammalian circadian function, as these mutations were semidominant. CLOCK protein has been found to play

7544-431: The timing mechanism of the circadian clock. A similar model is found in mice, in which BMAL1 dimerizes with CLOCK to activate per and cryptochrome ( cry ) transcription. PER and CRY proteins form a heterodimer which acts on the CLOCK-BMAL heterodimer to repress the transcription of per and cry . The heterodimer CLOCK:BMAL1 functions similarly to other transcriptional activator complexes; CLOCK:BMAL1 interacts with

7636-694: The timing of sleep, and other disorders including ones caused by medical or psychological conditions. When a person struggles to fall asleep or stay asleep with no obvious cause , it is referred to as insomnia , which is the most common sleep disorder. Others include sleep apnea , narcolepsy and hypersomnia (excessive sleepiness at inappropriate times), sleeping sickness (disruption of sleep cycle due to infection), sleepwalking , and night terrors . Sleep disruptions can be caused by various issues, including teeth grinding ( bruxism ) and night terrors. Management of sleep disturbances that are secondary to mental, medical or substance abuse disorders should focus on

7728-448: The treatment of sleep disorders in both adults and children. Although more research should be done to increase the reliability of this method of treatment, research suggests that music therapy can improve sleep quality in acute and chronic sleep disorders. In one particular study, participants (18 years or older) who had experienced acute or chronic sleep disorders were put in a randomly controlled trial, and their sleep efficiency, in

7820-534: The treatments of the disease. The neurodegenerative conditions are commonly related to structural brain impairment, which might disrupt the states of sleep and wakefulness, circadian rhythm, motor or non motor functioning. On the other hand, sleep disturbances are frequently related to worsening patient's cognitive functioning, emotional state and quality of life. Furthermore, these abnormal behavioral symptoms negatively contribute to overwhelming their relatives and caregivers. The limited research related to it and

7912-462: The two most common sleep disorders among children. An estimated 17.3% of kids between 3 and 13 years old experience confusional arousals. About 17% of children sleepwalk, with the disorder being more common among boys than girls, the peak ages of sleepwalking are from 8 to 12 years old. A different systematic review offers a high range of prevalence rates of sleep bruxism for children. Parasomnias like sleepwalking and talking typically occur during

8004-457: The underlying conditions. Primary sleep disorders are common in both children and adults. However, there is a significant lack of awareness of children with sleep disorders, due to most cases being unidentified. Several common factors involved in the onset of a sleep disorder include increased medication use, age-related changes in circadian rhythms, environmental changes, lifestyle changes, pre-diagnosed physiological problems, or stress. Among

8096-524: The underlying conditions. Medications and somatic treatments may provide the most rapid symptomatic relief from certain disorders, such as narcolepsy, which is best treated with prescription drugs such as modafinil . Others, such as chronic and primary insomnia, may be more amenable to behavioral interventions—with more durable results. Chronic sleep disorders in childhood, which affect some 70% of children with developmental or psychological disorders, are under-reported and under-treated. Sleep-phase disruption

8188-598: The varying situations differs greatly and cannot be undertaken without a correct diagnosis. Sleep dentistry ( bruxism , snoring and sleep apnea ), while not recognized as one of the nine dental specialties , qualifies for board-certification by the American Board of Dental Sleep Medicine (ABDSM). The qualified dentists collaborate with sleep physicians at accredited sleep centers, and can provide oral appliance therapy and upper airway surgery to treat or manage sleep-related breathing disorders. The resulting diplomate status

8280-416: The wild-type protein. The presence of an antimorphic protein downregulates the transcriptional products normally upregulated by Clock . In Drosophila , a mutant form of Clock ( Jrk ) was identified by Allada, Hall , and Rosbash in 1998. The team used forward genetics to identify non-circadian rhythms in mutant flies. Jrk results from a premature stop codon that eliminates the activation domain of

8372-472: Was observed, suggesting a molecular mechanism for cortical expansion unique to human brain development. However, the precise role of CLOCK in metabolic regulation of cortical neurons remains to be determined. Another study looking at the relationship between CLOCK polymorphisms in the 3’ flanking region and morning/evening preference in adults found a correlation between subjects with the 3111C allele and preference for evening hours based on answers provided in

8464-563: Was reported in 78% of the SCZ population, in 69% individuals with BD, and in 39% of healthy controls. The SCZ group reported the most number of sleep disturbances compared to the BD and HC groups; specifically, hypersomnia was more frequent among individuals with SCZ, and delayed sleep phase disorder was three times more common in the SCZ group compared to the BD group. Insomnias were the most frequently reported sleep disturbance across all three groups. One of

#526473