Sleep Disorders

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Sleep Disorders

Connections with ASD

Sleep disturbances are frequently observed in individuals with ASD. It has been hypothesized that abnormal melatonin synthesis found in those with ASD may influence the susceptibility to the syndrome because melatonin is one of the factors that sets the internal clock to a 24-hour cycle and is crucial for regulating the sleep/wake (S/W) cycle, which is needed for appropriate cognitive development.1 In one study which subdivided individuals with ASD based off of cluster analysis of ADI-R scores, investigators were able to see that there was dysregulation in the circadian rhythm genes in the subgroup that displayed the most severe deficits according to ADI-R scores versus those mildly affected or with savant abilities. There were 15 genes responsible for circadian rhythms identified within this subgroup that were subject to abnormal expression levels. People in the severe ASD subgroup often had abnormal genetic variants in many of the 15 genes, though not all. These genes, in addition to regulating circadian rhythm, also affect synaptic plasticity, learning, memory, inflammation, cytokine production, and digestion thus implicating circadian rhythm systemic effects in endocrine, gastrointestinal and cardiovascular functions. It has been proposed then that interventions that normalize the circadian rhythms may alleviate the symptoms that are associated with ASD for this particular subgroup.2

Melatonin is a hormone produced by the pineal gland. Melatonin is converted from serotonin to N-acetylseretonin which is then converted to Hydroxyindole O-methyltransferase (HIOMT). A deficiency in HIOMT could cause melatonin synthesis problems, which indicates melatonin synthesis is not a consequence of ASD, but could result from a deficiency in HIOMT. So it could be that the sleeping disorder is a separate issue from the diagnosis of ASD. However the higher incidence of sleep disorders diagnosed in the ASD population as compared to the typically developing population suggests a link between the two disorders.

It has been hypothesized that the sleep/wake biological pathways may modulate pathways in the expression of synaptic genes such as NLGN3/4, SHANK3, or the neurexins. There are a large amount of studies that support the involvement of synaptic genes in raising susceptibility to ASD. However, there have been few studies that have directly investigated if these two pathways interact with each other. Melatonin has been shown alter the phosphorylation of CREB which is important for memory consolidation. Additionally melatonin signficantly inhibits synaptic transmission and long-term potentiation through modulation of GABAergic system, which shows that melatonin does affect some aspects of learning. 1

Treatments

Citations

1. Bourgeron T. The possible interplay of synaptic and clock genes in autism spectrum disorders.Cold Spring Harb Symp Quant Biol. 2007;72:645-54. PMID 18419324

2. Hu, VW et. al.Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism. Autism Res. 2009 May 5. PMID 19418574