Advanced sleep phase syndrome
Encyclopedia
Advanced sleep phase syndrome (ASPS), also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder
, is a condition in which patients feel very sleepy and go to bed early in the evening (e.g. 6:00–8:00 p.m.) and wake up very early in the morning (e.g. 1:00–3:00 a.m.).
ASPS is more frequently encountered in the elderly and in post-menopausal women than in younger people.
and falling asleep early in the evening. When someone has advanced sleep phase syndrome their melatonin
levels and core body temperature will cycle hours earlier than the average person. These symptoms must be present for at least three months in order to be correctly diagnosed.
in the evenings, or behaviorally with chronotherapy
. Unlike other sleep disorders, ASPS does not disrupt normal functioning to work during the day and the patient does not complain of excessive daytime sleepiness. If their ASPS is causing people to lose out on evening activities, including putting their own normal children to bed, then they can force themselves to stay up later than their circadian rhythm wants them to. A sufferer of ASPS will still wake up very early and if this cycle continues it can lead to chronic sleep deprivation and other sleep disorders.
reported findings of a human circadian rhythm
disorder showing a familial tendency. The disorder was characterized by a life-long pattern of sleep onset around 7:30 p.m. and offset around 4:30 a.m. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase syndrome (FASPS), and 46 were considered unaffected. The pedigrees demonstrated FASPS to be a highly penetrant, autosomal dominant trait.
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 chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro.
In 2005, Fu's and Ptáček's labs reported discovery of a different mutation causing FASPS. This time, CKIδ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein. The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects and by demonstration of functional consequences of the respective mutations in vitro. 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 differences between flies and mammals that account for this difference are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that CKIδ is having opposite effects on Per2 levels depending on the sites on Per2 that CKIδ is phosphorylating.
Circadian rhythm sleep disorder
Circadian rhythm sleep disorders are a family of sleep disorders affecting, among other things, the timing of sleep. People with circadian rhythm sleep disorders are unable to sleep and wake at the times required for normal work, school, and social needs. They are generally able to get enough sleep...
, is a condition in which patients feel very sleepy and go to bed early in the evening (e.g. 6:00–8:00 p.m.) and wake up very early in the morning (e.g. 1:00–3:00 a.m.).
ASPS is more frequently encountered in the elderly and in post-menopausal women than in younger people.
Symptoms
People with ASPS are unable to stay awake until their desired bedtime and unable to stay asleep until their desired waking time. They will complain to a sleep clinician of early morning insomniaInsomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
and falling asleep early in the evening. When someone has advanced sleep phase syndrome their melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
levels and core body temperature will cycle hours earlier than the average person. These symptoms must be present for at least three months in order to be correctly diagnosed.
Epidemiology
ASPS is a rare disorder. It affects both men and women equally and has been determined to have a strong genetic link with 40–50% of people related to someone with ASPS having it themselves. As stated below, several genes have been discovered to have links with this syndrome and the body's circadian rhythms. Although it can be impairing, the syndrome is not necessarily unhealthy; most people don't seek help unless it starts to severely impact their social life.Treatment
Once diagnosed ASPS can be treated with bright light therapyLight therapy
Light therapy or phototherapy consists of exposure to daylight or to specific wavelengths of light using lasers, light-emitting diodes, fluorescent lamps, dichroic lamps or very bright, full-spectrum light, usually controlled with various devices...
in the evenings, or behaviorally with chronotherapy
Chronotherapy
People who suffer from delayed sleep phase syndrome are generally unable to reset their circadian rhythm by moving their bedtime and rising time earlier...
. Unlike other sleep disorders, ASPS does not disrupt normal functioning to work during the day and the patient does not complain of excessive daytime sleepiness. If their ASPS is causing people to lose out on evening activities, including putting their own normal children to bed, then they can force themselves to stay up later than their circadian rhythm wants them to. A sufferer of ASPS will still wake up very early and if this cycle continues it can lead to chronic sleep deprivation and other sleep disorders.
Familial advanced sleep phase syndrome
In 1999, Louis Ptáček's research group at the University of California, San FranciscoUniversity of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
reported findings of a human circadian rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
disorder showing a familial tendency. The disorder was characterized by a life-long pattern of sleep onset around 7:30 p.m. and offset around 4:30 a.m. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase syndrome (FASPS), and 46 were considered unaffected. The pedigrees demonstrated FASPS to be a highly penetrant, autosomal dominant trait.
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 chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro.
In 2005, Fu's and Ptáček's labs reported discovery of a different mutation causing FASPS. This time, CKIδ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein. The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects and by demonstration of functional consequences of the respective mutations in vitro. 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 differences between flies and mammals that account for this difference are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that CKIδ is having opposite effects on Per2 levels depending on the sites on Per2 that CKIδ is phosphorylating.
See also
- Circadian rhythm sleep disorderCircadian rhythm sleep disorderCircadian rhythm sleep disorders are a family of sleep disorders affecting, among other things, the timing of sleep. People with circadian rhythm sleep disorders are unable to sleep and wake at the times required for normal work, school, and social needs. They are generally able to get enough sleep...
- Delayed sleep phase syndromeDelayed sleep phase syndromeDelayed sleep-phase syndrome , also known as delayed sleep-phase disorder or delayed sleep-phase type , is a circadian rhythm sleep disorder, a chronic disorder of the timing of sleep, peak period of alertness, the core body temperature rhythm, hormonal and other daily rhythms, compared to the...
- Non-24-hour sleep-wake syndromeNon-24-hour sleep-wake syndromeNon-24-hour sleep-wake syndrome is a chronic circadian rhythm sleep disorder, classified within Chapter VI, Diseases of the Nervous System, in the ICD-10. It can be defined as "a chronic steady pattern comprising one- to two-hour daily delays in sleep onset and wake times in an individual living...
- Irregular sleep-wake rhythmIrregular sleep-wake rhythmIrregular sleep–wake rhythm 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. Sufferers have no pattern of when they are awake or asleep, may have poor quality...