275:, a structured self-assessment questionnaire used to determine morningness-eveningness in human circadian rhythms. The Horne-Ă–stberg scores of first-degree relatives of affected individuals were higher than those of 'marry-in' spouses and unrelated control subjects. While much of morning and evening preference is heritable, the allele causing FASPS was hypothesized to have a quantitatively larger effect on clock function than the more common genetic variations that influence these preferences. Additionally, the circadian phase of subjects was determined using plasma
399:
individuals and by the observed change in the circadian phenotype of these mutant individuals in vitro and an absence of said mutations in all tested control subjects. Fruit flies and mice engineered to carry the human mutation also demonstrated abnormal circadian phenotypes, although the mutant flies had a long circadian period while the mutant mice had a shorter period. The genetic differences between flies and mammals that account for this difference circadian phenotypes are not known. Most recently, Ptáček and Fu reported additional studies of the human
324:
245:. Diagnosis of FASPS can be confirmed through genetic sequencing analysis by locating genetic mutations known to cause the disorder. Treatment with sleep and wake scheduling and bright light therapy can be used to try to delay sleep phase to a more conventional time frame, however treatment of FASPS has proven largely unsuccessful. Bright light exposure in the evening (between 7:00 and 9:00), during the delay zone as indicated by the
211:, with 40-50% of affected individuals having relatives with ASPD. A genetic basis has been demonstrated in one form of ASPD, familial advanced sleep phase syndrome (FASPS), which implicates missense mutations in genes hPER2 and CKIdelta in producing the advanced sleep phase phenotype. The identification of two different genetic mutations suggests that there is heterogeneity of this disorder.
394:. This is consistent with studies of the role of CK1ɛ (a unique member of the CK1 family) in the TTFL in mammals and more studies have been conducted looking at specific regions of the Per2 transcript. In 2005, Fu's and Ptáček's labs reported discovery of a mutation in CKIδ (a functionally redundant form of CK1ɛ in the phosphorylation process of PER2) also causing FASPS. An A-to-G
112:, is a condition that is characterized by a recurrent pattern of early evening (e.g. 7-9 PM) sleepiness and very early morning awakening (e.g. 2-4 AM). 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
150:
389:
mRNA is transcribed and the period is shortened to less than 24 hours. Individuals with a shortened period due to this phosphorylation disruption entrain to a 24h light-dark cycle, which may lead to a phase advance, causing earlier sleep and wake patterns. However, a 22h period does not necessitate a
224:
While advanced sleep and wake times are relatively common, especially among older adults, the extreme phase advance characteristic of familial advanced sleep phase syndrome (also known as familial advanced sleep phase disorder) is rare. Individuals with FASPS fall asleep and wake up 4–6 hours earlier
229:
of 22 hours, which is significantly shorter than the average human period of slightly over 24 hours. The shortened period associated with FASPS results in a shortened period of activity, causing earlier sleep onset and offset. This means that individuals with FASPS must delay their sleep onset and
194:
have been proposed, but determining their safety and efficacy will require further research. Unlike other sleep disorders, ASPD does not necessarily disrupt normal functioning at work during the day and some patients may not complain of excessive daytime sleepiness. Social obligations may cause an
265:
after identifying individuals with a genetic basis for an advanced sleep phase. The first patient evaluated during the study reported "disabling early evening sleepiness" and "early morning awakening"; similar symptoms were also reported in her family members. Consenting relatives of the initial
314:
in producing the FASPS behavioral phenotype. FASPS is the first disorder to link known core clock genes directly with human circadian sleep disorders. As the PER2 mutation is not exclusively responsible for causing FASPS, current research has continued to evaluate cases in order to identify new
270:
patterns of subject families were used to define a hereditary circadian rhythm variant associated with a short endogenous (i.e. internally-derived) period. The subjects demonstrated a phase advance of sleep-wake rhythms that was distinct not only from control subjects, but also to sleep-wake
294:
phenotypically characterized an additional family affected with ASPS. This study involved an analysis of sleep/wake patterns, diurnal preferences (using a Horne-Ă–stberg questionnaire), and the construction of a pedigree for the affected family. Consistent with established ASPS criteria, the
398:
resulted in a threonine-to-alanine alteration in the protein. This mutation prevented the proper phosphorylation of PER2. The evidence for both a mutation in the binding domain of PER2 and a mutation in CKIδ as causes of FASPS is strengthened by the lack of the FASPS phenotype in wild type
240:
Another factor that distinguishes FASPS from other advanced sleep phase disorders is its strong familial tendency and life-long expression. Studies of affected lineages have found that approximately 50% of directly related family members experience the symptoms of FASPS, which is an
299:. Furthermore, the identified family was one in which an ASPS-affected member was present in every generation; consistent with earlier work done by the Ptáček group, this pattern suggests that the phenotype segregates as a single gene with an autosomal dominant mode of inheritance.
891:
Jones, Christopher R.; Campbell, Scott S.; Zone, Stephanie E.; Cooper, Fred; DeSano, Alison; Murphy, Patricia J.; Jones, Bryan; Czajkowski, Laura; PtÄŤek, Louis J. (1999). "Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans".
377:
mRNA. CK1 regulates PER2 levels by binding to a CK1 binding site on the protein, allowing for phosphorylation which marks the protein for degradation, reducing protein levels. Once proteins become phosphorylated, PER2 levels decrease again, and
230:
offset each day in order to entrain to the 24-hour day. On holidays and weekends, when the average person's sleep phase is delayed relative to their workday sleep phase, individuals with FASPS experience further advance in their sleep phase.
1504:
1489:
1474:
186:, in order to delay sleep onset and offset. The use of pharmacological approaches to treatment are less successful due to the risks of administering sleep-promoting agents early in the morning. Additional methods of treatment, like timed
132:
Individuals with ASPD report being unable to stay awake until conventional bedtime, falling asleep too quickly and/or early in the evening, and being unable to stay asleep until their desired waking time, experiencing early morning
295:
evaluation of subject sleep architecture indicated that the advanced sleep phase was due to an alteration of circadian timing rather than an exogenous (i.e. externally-derived) disruption of sleep homeostasis, a mechanism of
157:
Individuals expressing the above symptoms may be diagnosed with ASPD using a variety of methods and tests. Sleep specialists measure the patient's sleep onset and offset, dim light melatonin onset, and evaluate
403:
S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals under constant darkness. Genetic dosage studies of CKIδ on the
207:
ASPD is more common among middle and older adults. The estimated prevalence of ASPD is about 1% in middle-age adults, and is believed to affect men and women equally. The disorder has a strong
233:
Aside from the unusual timing of sleep, FASPS patients experience normal quality and quantity of sleep. Like general ASPD, this syndrome does not inherently cause negative impacts, however,
331:
Two years after reporting the finding of FASPS, Ptáček's and Fu's groups published results of genetic sequencing analysis on a family with FASPS. They genetically mapped the FASPS locus to
195:
individual to stay up later than their circadian rhythm requires, however, they will still wake up very early. If this cycle continues, it can lead to chronic sleep deprivation and other
141:
levels and core body temperature cycle hours earlier than an average person. These symptoms must be present and stable for a substantial period of time to be correctly diagnosed.
279:
and body core temperature measurements; these rhythms were both phase-advanced by 3–4 hours in FASPS subjects compared with control subjects. The Ptáček group also constructed a
1198:
Vanselow, Katja; Vanselow, Jens T.; Westermark, PĂĄl O.; Reischl, Silke; Maier, Bert; Korte, Thomas; Herrmann, Andreas; Herzel, Hanspeter; Schlosser, Andreas (1 October 2006).
237:
may be imposed by social norms causing individuals to delay sleep until a more socially acceptable time, causing them to losing sleep due to earlier-than-usual wakeup time.
1355:
Xu, Ying; Quasar S. Padiath; Robert E. Shapiro; et al. (31 March 2005). "Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome".
2260:
579:"Circadian Rhythm Sleep Disorders: Part II, Advanced Sleep Phase Disorder, Delayed Sleep Phase Disorder, Free-Running Disorder, and Irregular Sleep-Wake Rhythm"
249:
to light, has been shown to delay circadian rhythms, resulting in later sleep onset and offset in patients with FASPS or other advanced sleep phase disorders.
756:
Tafti, Mehdi; Dauvilliers, Yves; Overeem, Sebastiaan (2007). "Narcolepsy and familial advanced sleep-phase syndrome: molecular genetics of sleep disorders".
335:
where very little human genome sequencing was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was
1873:
577:
Zhdanova, Irina V.; Vitiello, Michael V.; Wright, Kenneth P.; Carskadon, Mary A.; Auger, R. Robert; Auckley, Dennis; Sack, Robert L. (1 November 2007).
272:
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Yang, Yu; Xu, Tingting; Zhang, Yunfei; Qin, Ximing (2017). "Molecular basis for the regulation of the circadian clock kinases CK1δ and CK1ε".
159:
1835:
435:
943:
Reid, Kathryn J.; Chang, Anne-Marie; Dubocovich, Margarita L.; Turek, Fred W.; Takahashi, Joseph S.; Zee, Phyllis C. (1 July 2001).
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mRNA is transcribed and translated to form a PER2 protein. Large concentrations of PER2 protein inhibits further transcription of
1713:
1708:
1680:
1825:
430:
1868:
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mRNA transcription can resume. This negative feedback regulates the levels and expression of these circadian clock components.
109:
1200:"Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS)"
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1948:
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phase shift, but a shift can be predicted depending on the time the subject is exposed to the stimulus, visualized on a
1953:
1815:
1763:
997:
Toh, K. L. (9 February 2001). "An hPer2 Phosphorylation Site
Mutation in Familial Advanced Sleep Phase Syndrome".
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2031:
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2250:
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published a genetic analysis of subjects experiencing the advanced sleep phase, implicating a mutation in the
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patient were evaluated, as well as those from two additional families. The clinical histories, sleep logs and
2128:
1909:
1718:
117:
62:
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gene ('h' denoting a human strain, as opposed to
Drosophila or mouse strains) revealed a serine-to-glycine
2224:
1773:
1608:
187:
2046:
1778:
296:
208:
1255:
Menaker, M.; Ralph, M. R. (2 September 1988). "A mutation of the circadian system in golden hamsters".
2200:
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1006:
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than the average population, generally sleeping from 7:30pm to 4:30am. They also have a free running
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Without proper phosphorylation of hPER2 in the instance of a mutation in the CK1 binding site, less
2195:
2185:
1651:
1551:
1508:
345:) which is a mammalian gene sufficient for the maintenance of circadian rhythms. Sequencing of the
2205:
1958:
1858:
1723:
1388:
1137:
1050:"The genetics of mammalian circadian order and disorder: implications for physiology and disease"
1030:
925:
369:(TTFL) required for regulating the stable production of hPER2 protein. In a wildtype individual,
52:
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of hPER2 in vitro. The hypophosphorylation of hPER2 disrupts the transcription-translation
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schedules widely considered to be conventional. The subjects were also evaluated using the
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2008:
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226:
196:
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113:
1368:
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791:
Pack, Allan I.; Pien, Grace W. (18 February 2011). "Update on Sleep and Its
Disorders".
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1968:
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1408:"Modeling of a Human Circadian Mutation Yields Insights into Clock Regulation by PER2"
1308:"Modeling of a human circadian mutation yields insights into clock regulation by PER2"
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Takahashi, Joseph S.; Hong, Hee-Kyung; Ko, Caroline H.; McDearmon, Erin L. (2008).
1034:
332:
121:
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Among other methods, sleep studies, or polysomnography, are used to diagnose ASPD.
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2160:
2036:
1976:
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1914:
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1703:
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1580:
696:
Jones, Christopher R.; Huang, Angela L.; Ptáček, Louis J.; Fu, Ying-Hui (2013).
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that CK1δ interacts with, CK1δ may lead to hypo- or hyperphosphorylation of the
303:
72:
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1323:
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Reid KJ, Chang AM, Dubocovich ML, Turek FW, Takahashi JS, Zee PC (July 2001).
267:
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Xu, Y.; Toh, K.L.; Jones, C.R.; Shin, J.-Y.; Fu, Y.-H.; Ptáček, L.J. (2007).
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2003:
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Xu, Ying; Kong L. Toh; Christopher R. Jones; et al. (12 January 2007).
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170:. Age and family history of the patient is also taken into consideration.
2096:
2071:
1991:
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134:
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conducted a study at the
University of Utah in which he coined the term
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1996:
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564:"Advanced Sleep-Wake Phase Disorder - Symptoms, Diagnosis, Treatment"
1065:
563:
87:
Polysomnography, Horne-Ostberg morningness-eveningness questionnaire
2086:
1904:
1567:
905:
336:
311:
1540:
836:"Genetic insights on sleep schedules: this time, it's PERsonal"
2170:
2066:
408:
S662G mutation revealed that depending on the binding site on
327:
A molecular model of the mammalian circadian clock mechanism.
108:), also known as the advanced sleep-phase type (ASPT) of
137:. When someone has advanced sleep phase disorder their
1456:
283:
of the three FASPS kindreds which indicated a clear
2059:
2019:
1967:
1897:
1849:
1797:
1739:
1679:
1670:
1607:
1578:
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698:"Genetic Basis of Human Circadian Rhythm Disorders"
464:"Therapeutics for Circadian Rhythm Sleep Disorders"
160:
Horne-Ostberg morningness-eveningness questionnaire
91:
81:
71:
61:
51:
39:
34:
178:Once diagnosed, ASPD may be treated with bright
834:Fu, Y. H.; Ptáček, L. J.; Chong, S. Y. (2012).
162:results. Sleep specialists may also conduct a
57:Earlier than desired onset and offset of sleep
1552:
758:Current Opinion in Genetics & Development
8:
166:test to rule out other sleep disorders like
315:mutations that contribute to the disorder.
302:In 2001, the research groups of Ptáček and
1874:Rapid eye movement sleep behavior disorder
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31:
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1081:
960:
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729:
672:
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462:Dodson, Ehren R.; Zee, Phyllis C (2010).
287:transmission of the sleep phase advance.
945:"Familial Advanced Sleep Phase Syndrome"
524:"Familial advanced sleep phase syndrome"
322:
148:
447:
2261:Syndromes affecting the nervous system
992:
990:
988:
361:of the hPER2 protein that resulted in
263:familial advanced sleep phase disorder
215:Familial advanced sleep phase syndrome
182:in the evenings, or behaviorally with
639:Zhu, Lirong; Zee, Phyllis C. (2012).
634:
632:
630:
457:
455:
453:
451:
7:
751:
749:
517:
515:
1107:"Entrainment of Circadian Programs"
95:Bright light therapy, chronotherapy
641:"Circadian Rhythm Sleep Disorders"
25:
805:10.1146/annurev-med-050409-104056
1714:Obesity hypoventilation syndrome
1709:Central hypoventilation syndrome
1869:Periodic limb movement disorder
1836:Non-24-hour sleep–wake disorder
714:10.1016/j.expneurol.2012.07.012
436:Non-24-hour sleep–wake disorder
290:In 2001, the research group of
110:circadian rhythm sleep disorder
1:
2141:Biphasic and polyphasic sleep
1949:Nocturnal clitoral tumescence
1811:Advanced sleep phase disorder
1169:10.1016/j.cellsig.2016.12.010
102:Advanced Sleep Phase Disorder
35:Advanced Sleep Phase Disorder
18:Advanced sleep phase syndrome
1821:Delayed sleep phase disorder
1749:Excessive daytime sleepiness
426:Delayed sleep phase disorder
77:Increased incidence with age
1954:Nocturnal penile tumescence
1826:Irregular sleep–wake rhythm
1114:Chronobiology International
431:Irregular sleep–wake rhythm
273:Horne-Ă–stberg questionnaire
2282:
1816:Cyclic alternating pattern
1424:10.1016/j.cell.2006.11.043
1324:10.1016/j.cell.2006.11.043
962:10.1001/archneur.58.7.1089
541:10.1001/archneur.58.7.1089
480:10.1016/j.jsmc.2010.08.001
392:Phase Response Curve (PRC)
116:, which is located in the
2032:Behavioral sleep medicine
1841:Shift work sleep disorder
1789:Sleep state misperception
1105:Johnson, Carl H. (2013).
852:10.1016/j.tig.2012.08.002
793:Annual Review of Medicine
770:10.1016/j.gde.2007.04.007
657:10.1016/j.ncl.2012.08.011
319:Mechanisms (Per2 and CK1)
1589:Rapid eye movement (REM)
595:10.1093/sleep/30.11.1484
367:(negative) feedback loop
243:autosomal dominant trait
1910:Exploding head syndrome
1719:Obstructive sleep apnea
1277:10.1126/science.3413487
1204:Genes & Development
1054:Nature Reviews Genetics
1019:10.1126/science.1057499
118:suprachiasmatic nucleus
2225:Sleeping while on duty
1774:Idiopathic hypersomnia
702:Experimental Neurology
468:Sleep Medicine Clinics
328:
154:
2047:Neuroscience of sleep
1779:Night eating syndrome
1764:Kleine–Levin syndrome
1126:10.1081/CBI-120024211
949:Archives of Neurology
528:Archives of Neurology
326:
152:
2201:Sleep and creativity
247:phase response curve
2196:Sleep and breathing
1652:Sensorimotor rhythm
1377:10.1038/nature03453
1369:2005Natur.434..640X
1269:1988Sci...241.1225R
1263:(4870): 1225–1227.
1157:Cellular Signalling
1011:2001Sci...291.1040T
1005:(5506): 1040–1043.
363:hypophosphorylation
310:-binding region of
2206:Sleep and learning
1959:Nocturnal emission
1859:Nightmare disorder
1724:Periodic breathing
1216:10.1101/gad.397006
840:Trends in Genetics
645:Neurologic Clinics
329:
285:autosomal dominant
190:administration or
155:
2238:
2237:
2216:Sleep deprivation
2055:
2054:
1534:
1533:
1363:(7033): 640–644.
1210:(19): 2660–2672.
589:(11): 1484–1501.
396:missense mutation
235:sleep deprivation
209:familial tendency
99:
98:
83:Diagnostic method
67:Sleep deprivation
29:Medical condition
16:(Redirected from
2273:
2266:Sleep physiology
2256:Circadian rhythm
2211:Sleep and memory
2151:Circadian rhythm
1898:Benign phenomena
1800:Circadian rhythm
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900:(9): 1062–1065.
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651:(4): 1167–1191.
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227:circadian period
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2129:Procrastination
2082:Four-poster bed
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2015:
2009:Polysomnography
1987:Sleep induction
1963:
1934:Sleep paralysis
1893:
1845:
1804:
1801:
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1735:
1694:Mouth breathing
1672:Sleep disorders
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1594:Quiescent sleep
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1572:sleep disorders
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1066:10.1038/nrg2430
1060:(10): 764–775.
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894:Nature Medicine
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846:(12): 598–605.
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355:Casein Kinase I
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197:sleep disorders
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164:polysomnography
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114:circadian clock
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2156:Comfort object
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1461:Classification
1454:
1453:External links
1451:
1448:
1447:
1398:
1347:
1298:
1247:
1190:
1147:
1120:(5): 741–774.
1097:
1040:
984:
955:(7): 1089–94.
935:
883:
826:
799:(1): 447–460.
783:
764:(3): 222–227.
745:
688:
626:
569:
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534:(7): 1089–94.
511:
474:(4): 701–715.
446:
445:
443:
440:
439:
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433:
428:
421:
418:
359:binding domain
351:point mutation
320:
317:
292:Phyllis C. Zee
254:
251:
221:
220:FASPS symptoms
218:
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204:
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2018:
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1982:Sleep hygiene
1980:
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1947:
1945:
1942:
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1939:Sleep inertia
1937:
1935:
1932:
1930:
1927:
1925:
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1913:
1911:
1908:
1906:
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1889:Sleep-talking
1887:
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1884:Sleep driving
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1657:Sleep spindle
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388:
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339:
334:
333:chromosome 2q
325:
318:
316:
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185:
184:chronotherapy
181:
180:light therapy
173:
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144:
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123:
119:
115:
111:
107:
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94:
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86:
84:
80:
76:
74:
70:
66:
64:
63:Complications
60:
56:
54:
50:
47:
46:Chronobiology
44:
42:
38:
33:
27:
19:
2102:Sleeping bag
1879:Sleepwalking
1864:Night terror
1810:
1581:sleep cycles
1518:
1503:
1488:
1473:
1418:(1): 59–70.
1415:
1411:
1401:
1360:
1356:
1350:
1318:(1): 59–70.
1315:
1311:
1301:
1260:
1256:
1250:
1207:
1203:
1193:
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386:
384:
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346:
342:
337:
330:
301:
289:
262:
259:Louis Ptáček
256:
239:
232:
223:
206:
203:Epidemiology
177:
156:
131:
122:hypothalamus
105:
101:
100:
73:Risk factors
26:
2186:Second wind
2161:Dream diary
2037:Sleep study
1977:Sleep diary
1929:Hypnopompia
1924:Sleep onset
1915:Hypnic jerk
1754:Hypersomnia
1704:Catathrenia
1699:Sleep apnea
1609:Brain waves
1579:Stages of
304:Ying-Hui Fu
2245:Categories
2220:Sleep debt
2166:Microsleep
2146:Chronotype
2060:Daily life
1944:Somnolence
1920:Hypnagogia
1851:Parasomnia
1769:Narcolepsy
1681:Anatomical
1662:Theta wave
1632:Gamma wave
1627:Delta wave
1617:Alpha wave
442:References
268:actigraphy
168:narcolepsy
2230:Sleepover
2181:Power nap
2176:Nightwear
2042:Melatonin
2004:Somnology
1969:Treatment
1802:disorders
1741:Dyssomnia
1647:PGO waves
1642:Mu rhythm
1637:K-complex
1622:Beta wave
1599:Slow-wave
1285:0036-8075
1224:0890-9369
1177:0898-6568
1163:: 58–65.
1074:1471-0056
971:0003-9942
914:1078-8956
860:0168-9525
813:0066-4219
722:0014-4886
708:: 28–33.
665:0733-8619
603:0161-8105
488:1556-407X
277:melatonin
257:In 1999,
253:Discovery
192:hypnotics
188:melatonin
174:Treatment
145:Diagnosis
139:melatonin
92:Treatment
41:Specialty
2097:Mattress
2072:Bunk bed
1992:Hypnosis
1784:Nocturia
1759:Insomnia
1442:17218255
1385:15800623
1342:17218255
1242:16983144
1185:28057520
1142:16424964
1134:14535352
1092:18802415
1027:11232563
979:11448298
930:14809619
922:10470086
878:22939700
821:21073334
778:17467264
740:22849821
683:23099133
621:18041481
550:11448298
506:21243069
420:See also
281:pedigree
135:insomnia
128:Symptoms
53:Symptoms
2124:Bedtime
2119:Bedroom
2114:Bedding
2109:Bed bug
2092:Hammock
1997:Lullaby
1831:Jet lag
1731:Snoring
1689:Bruxism
1525:D020178
1433:1828903
1393:4416575
1365:Bibcode
1333:1828903
1293:3413487
1265:Bibcode
1257:Science
1233:1578693
1083:3758473
1035:1848310
1007:Bibcode
999:Science
869:3500418
731:3514403
674:3523094
612:2082099
497:3020104
353:in the
338:Period2
120:in the
2191:Siesta
2077:Daybed
1905:Dreams
1514:327.32
1499:G47.22
1440:
1430:
1391:
1383:
1357:Nature
1340:
1330:
1291:
1283:
1240:
1230:
1222:
1183:
1175:
1140:
1132:
1090:
1080:
1072:
1033:
1025:
977:
969:
928:
920:
912:
876:
866:
858:
819:
811:
776:
738:
728:
720:
681:
671:
663:
619:
609:
601:
548:
504:
494:
486:
416:gene.
357:(CK1)
2134:Story
2087:Futon
2020:Other
1568:Sleep
1389:S2CID
1138:S2CID
1110:(PDF)
1031:S2CID
926:S2CID
583:Sleep
347:hPer2
1570:and
1520:MeSH
1509:9-CM
1484:7A61
1438:PMID
1412:Cell
1381:PMID
1338:PMID
1312:Cell
1289:PMID
1281:ISSN
1238:PMID
1220:ISSN
1181:PMID
1173:ISSN
1130:PMID
1088:PMID
1070:ISSN
1023:PMID
975:PMID
967:ISSN
918:PMID
910:ISSN
874:PMID
856:ISSN
817:PMID
809:ISSN
774:PMID
736:PMID
718:ISSN
679:PMID
661:ISSN
617:PMID
599:ISSN
546:PMID
502:PMID
484:ISSN
414:Per2
410:Per2
406:Per2
401:Per2
387:Per2
380:Per2
375:Per2
371:Per2
343:Per2
312:PER2
106:ASPD
2171:Nap
2067:Bed
1505:ICD
1490:ICD
1475:ICD
1428:PMC
1420:doi
1416:128
1373:doi
1361:434
1328:PMC
1320:doi
1316:128
1273:doi
1261:241
1228:PMC
1212:doi
1165:doi
1122:doi
1078:PMC
1062:doi
1015:doi
1003:291
957:doi
902:doi
864:PMC
848:doi
801:doi
766:doi
726:PMC
710:doi
706:243
669:PMC
653:doi
607:PMC
591:doi
536:doi
492:PMC
476:doi
308:CK1
2247::
2218:/
1922:/
1523::
1512::
1497::
1494:10
1482::
1479:11
1436:.
1426:.
1414:.
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1371:.
1359:.
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1314:.
1310:.
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1271:.
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1206:.
1202:.
1179:.
1171:.
1161:31
1159:.
1136:.
1128:.
1118:20
1116:.
1112:.
1086:.
1076:.
1068:.
1056:.
1052:.
1029:.
1021:.
1013:.
1001:.
987:^
973:.
965:.
953:58
951:.
947:.
924:.
916:.
908:.
896:.
872:.
862:.
854:.
844:28
842:.
838:.
815:.
807:.
797:62
795:.
772:.
762:17
760:.
748:^
734:.
724:.
716:.
704:.
700:.
677:.
667:.
659:.
649:30
647:.
643:.
629:^
615:.
605:.
597:.
587:30
585:.
581:.
544:.
532:58
530:.
526:.
514:^
500:.
490:.
482:.
470:.
466:.
450:^
199:.
124:.
1560:e
1553:t
1546:v
1507:-
1492:-
1477:-
1467:D
1444:.
1422::
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1375::
1367::
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1322::
1295:.
1275::
1267::
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1214::
1187:.
1167::
1144:.
1124::
1094:.
1064::
1058:9
1037:.
1017::
1009::
981:.
959::
932:.
904::
898:5
880:.
850::
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803::
780:.
768::
742:.
712::
685:.
655::
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552:.
538::
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478::
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341:(
104:(
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
