Advanced sleep phase disorder
[1] 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.
When someone has advanced sleep phase disorder their melatonin levels and core body temperature cycle hours earlier than an average person.
[2] Once diagnosed, ASPD may be treated with bright light therapy in the evenings, or behaviorally with chronotherapy, in order to delay sleep onset and offset.
[1] Additional methods of treatment, like timed melatonin administration or hypnotics have been proposed, but determining their safety and efficacy will require further research.
[4] 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.
[7] 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 autosomal dominant trait.
The clinical histories, sleep logs and actigraphy patterns of subject families were used to define a hereditary circadian rhythm variant associated with a short endogenous (i.e. internally-derived) period.
The Ptáček group also constructed a pedigree of the three FASPS kindreds which indicated a clear autosomal dominant transmission of the sleep phase advance.
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.
[11] In 2001, the research groups of Ptáček and Ying-Hui Fu published a genetic analysis of subjects experiencing the advanced sleep phase, implicating a mutation in the CK1-binding region of PER2 in producing the FASPS behavioral phenotype.
[citation needed] Without proper phosphorylation of hPER2 in the instance of a mutation in the CK1 binding site, less Per2 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.
[16][17] 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.
Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that depending on the binding site on Per2 that CK1δ interacts with, CK1δ may lead to hypo- or hyperphosphorylation of the Per2 gene.
