Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems

Garstang, Joanna; Wallis, Mark

doi:10.1111/j.1365-2214.2006.00616.x

Cited by 161 publications

(196 citation statements)

References 9 publications

(9 reference statements)

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“…[41][42][43][44] Taken together, these findings indicate that a subgroup of individuals with ASD and low melatonin levels could benefit from the use of melatonin as a therapeutic compound. Melatonin treatment seems to help patients with ASD to fall asleep and to sleep through the night, 37,[45][46][47][48] but it remains unknown if melatonin could have a more beneficial effect if given before 3 years of age. Further studies are required to determine the role of the melatonin deficit in the affected individuals, and more generally of circadian and seasonal rhythms, in the susceptibility to neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Abnormal melatonin synthesis in autism spectrum disorders

et al. 2007

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Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n = 250) and compared the allelic frequencies with controls (n = 255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P = 0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P = 2 Â 10 À10). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P = 2 Â 10 À12 ) and melatonin level (P = 3 Â 10 À11 ) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

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Section: Discussionmentioning

confidence: 99%

Abnormal melatonin synthesis in autism spectrum disorders

et al. 2007

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“…56 Several small RCTs demonstrated benefits in reducing SOL and in various quality of sleep measures in children with ASD. 57,58 Meta-analysis of three crossover studies indicated a significant improvement in SOL for melatonin over placebo in children with developmental disabilities. 59 Another small RCT (n ϭ 12) used a 4-week crossover design to evaluate the benefits of melatonin in children with ASD and children with fragile X syndrome.…”

Section: Biologically Based Practicesmentioning

confidence: 99%

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

2010

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Summary: This review focuses on helping clinicians identify resources and develop strategies they may use to effectively negotiate safe and effective use of complementary and alternative medicine (CAM) treatments with families of children with autism spectrum disorders (ASD), as well as other neurodevelopmental disorders. Since new types of CAM continue to be introduced into the autism community, emphasis is placed on providing clinicians with tools to help families negotiate the myriad of available treatments and make decisions based on current safety and efficacy data, while remaining mindful of the reasons families may be considering these treatments.We familiarize readers with high-quality, evidence-based resources that providers and families may use to ascertain current information about specific types of CAM, verify the content of biologically-based treatments, identify ongoing CAM research and obtain toolkits designed to help healthcare providers raise the topic of CAM usage and facilitate disclosure and discussion of CAM use with patients and their families. Key Words: Complementary and alternative medicine, autism, integrative medicine, gluten-free casein-free diet, melatonin, chelation, hyperbaric oxygen treatment, evidence-based medicine.

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“…Only two small-scale studies have tested the efficacy of melatonin in ASD (Garstang and Wallis 2006;Giannotti et al 2006). The first study evaluated openly the longterm effectiveness of controlled-release melatonin in 25 children, aged 2.6 to 9.6 years with ASD without other coexistent pathologies (Giannotti et al 2006).…”

Section: Melatonin Treatment In Autism Spectrum Disordersmentioning

confidence: 99%

“…No adverse side effects were reported. In the second study, a randomized, placebo-controlled double-blind crossover trial of melatonin was undertaken in 11 children with ASD (Garstang and Wallis 2006). All sleep parameters (sleep latency, waking per night, total sleep duration) were improved after treatment with melatonin.…”

Section: Melatonin Treatment In Autism Spectrum Disordersmentioning

confidence: 99%

The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders

Bourgeron¹

2007

Cold Spring Harbor Symposia on Quantitative Biology

160

124

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Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by deficits in social communication, absence or delay in language, and stereotyped and repetitive behaviors. Results from genetic studies reveal one pathway associated with susceptibility to ASD, which includes the synaptic cell adhesion molecules NLGN3, NLGN4, and NRXN1 and a postsynaptic scaffolding protein SHANK3. This protein complex is crucial for the maintenance of functional synapses as well as the adequate balance between neuronal excitation and inhibition. Among the factors that could modulate this pathway are the genes controlling circadian rhythms. Indeed, sleep disorders and low melatonin levels are frequently observed in ASD. In this context, an alteration of both this synaptic pathway and the setting of the clock would greatly increase the risk of ASD. In this chapter, I report genetic and neurobiological findings that highlight the major role of synaptic and clock genes in the susceptibility to ASD. On the basis of these lines of evidence, I propose that future studies of ASD should investigate the circadian modulation of synaptic function as a focus for functional analyses and the development of new therapeutic strategies.

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Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems

Abstract: Although the study was small owing to recruitment difficulties, it still provides evidence of effectiveness of melatonin in children with sleep difficulties and ASD, which we predict a larger study would confirm.

Cited by 161 publications

References 9 publications

Abnormal melatonin synthesis in autism spectrum disorders

Abnormal melatonin synthesis in autism spectrum disorders

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders

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