Dataset Information

Melatonin in Children with Autism Spectrum Disorders: How Does the Evidence Fit Together?

ABSTRACT: Autism spectrum disorders (ASD) are prevalent neurodevelopmental conditions, affecting 1 in 68 children in the United States alone. Sleep disturbance, particularly insomnia, is very common in children diagnosed with ASD, with evidence supporting overlapping neurobiological and genetic underpinnings. One of the most well studied mechanisms related to ASD and insomnia is dysregulation of the melatonin pathway, which has been observed in many individuals with ASD compared to typically developing controls. Furthermore, variation in genes whose products regulate endogenous melatonin modify sleep patterns in humans and have also been implicated in some cases of ASD. However, the relationship between comorbid insomnia, melatonin processing, and genes that regulate endogenous melatonin levels in ASD is complex and requires further study to fully elucidate. The aim of this review is to provide an overview of the current findings related to the effects of genetic variation in the melatonergic pathway on risk for expression of sleep disorders in children with ASD. In addition, functional findings related to endogenous levels of melatonin and pharmacokinetic profiles in this patient population are evaluated.

SUBMITTER: Veatch OJ

PROVIDER: S-EPMC4478596 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Melatonin in Children with Autism Spectrum Disorders: How Does the Evidence Fit Together?

Veatch Olivia J OJ Goldman Suzanne E SE Adkins Karen W KW Malow Beth A BA

Journal of nature and science 20150101 7

Autism spectrum disorders (ASD) are prevalent neurodevelopmental conditions, affecting 1 in 68 children in the United States alone. Sleep disturbance, particularly insomnia, is very common in children diagnosed with ASD, with evidence supporting overlapping neurobiological and genetic underpinnings. One of the most well studied mechanisms related to ASD and insomnia is dysregulation of the melatonin pathway, which has been observed in many individuals with ASD compared to typically developing co ...[more]

PMID: 26120597

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Project description:Purpose:This investigation was conducted to determine whether young children with autism spectrum disorders exhibited a canonical neural response to word stimuli and whether putative event-related potential (ERP) measures of word processing were correlated with a concurrent measure of receptive language. Additional exploratory analyses were used to examine whether the magnitude of the association between ERP measures of word processing and receptive language varied as a function of the number of word stimuli the participants reportedly understood. Method:Auditory ERPs were recorded in response to spoken words and nonwords presented with equal probability in 34 children aged 2-5 years with a diagnosis of autism spectrum disorder who were in the early stages of language acquisition. Average amplitudes and amplitude differences between word and nonword stimuli within 200-500 ms were examined at left temporal (T3) and parietal (P3) electrode clusters. Receptive vocabulary size and the number of experimental stimuli understood were concurrently measured using the MacArthur-Bates Communicative Development Inventories. Results:Across the entire participant group, word-nonword amplitude differences were diminished. The average word-nonword amplitude difference at T3 was related to receptive vocabulary only if 5 or more word stimuli were understood. Conclusions:If ERPs are to ever have clinical utility, their construct validity must be established by investigations that confirm their associations with predictably related constructs. These results contribute to accruing evidence, suggesting that a valid measure of auditory word processing can be derived from the left temporal response to words and nonwords. In addition, this measure can be useful even for participants who do not reportedly understand all of the words presented as experimental stimuli, though it will be important for researchers to track familiarity with word stimuli in future investigations. Supplemental Material:https://doi.org/10.23641/asha.5614840.

Project description:Flourishing is an indicator of positive mental health and is important for children's development and well-being. We used variables from the National Survey of Children's Health 2016 as indicators of flourishing (difficulty making friends, is bullied, bullies others, shares ideas with family, argues, finishes tasks, does all homework, shows curiosity, stays calm, and cares about doing well in school) to compare differences in parent perceptions of their children with and without autism spectrum disorder (ASD). We anticipate that these findings will help identify intervention targets to support the well-being of individuals with ASD. Children between 6 and 17 years of age, without intellectual disability, brain injury, cerebral palsy, or Down syndrome were included. Total participants were 34,171 controls (male/female = 17,116/17,155) and 812 with ASD (male/female = 668/144). Factor analysis resulted in three-factor structures (social competence, behavioral control, and school motivation) with good model fit (root mean square error of approximation = 0.08, comparative fit index = 0.92, Tucker-Lewis index = 0.89). The multivariate regression model and propensity score with inverse probability of treatment weighting (PS-IPTW) method revealed that children with ASD had lower scores in the social competence and behavioral control factors compared to the control group (all P < 0.05). However, no significant differences were found in the school motivation factor between the two groups (P > 0.05) in both multivariate regression model and PS-IPTW method. Findings suggest that social competence and behavioral control are indicators of flourishing and are important intervention targets to increase flourishing among children with ASD. Autism Res 2019, 12: 952-966. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Flourishing is an indicator of positive mental health and is important for children's development and well-being. We used variables from The National Survey of Children's Health 2016 to examine differences in parent perceptions of the indicators of flourishing (difficulty making friends, is bullied, bullies others, shares ideas with family, argues, finishes tasks, does all homework, shows curiosity, stays calm, and cares about doing well in school) between children with and without autism spectrum disorders (ASD). We anticipate that this information will help to identify therapeutic targets to support the well-being of individuals with ASD. Children between 6 and 17 years old, without intellectual disability (ID), brain injury (BI), cerebral palsy (CP), or Down syndrome (DS) were included. From the total (N = 50,212), we excluded children under age 6 (n = 14,494), those who once, but do not currently have ASD (n = 81), and those with ID (n = 432), BI (n = 170), CP (n = 35), and DS (n = 17), resulting in 34,983 records used. Total participants, age 6-17 years, were 34,171 controls (male/female = 17,116/17,155) and 812 with ASD (male/female = 668/144). Factor analysis resulted in the identification of three flourishing categories among the indicator variables (social competence, behavioral control, and school motivation). Children with ASD had lower scores in the social competence and behavioral control factors compared to the control group. However, there were no significant differences in the school motivation factor between the two groups. Findings suggest that social competence and behavioral control are indicators of flourishing and are important intervention targets to increase flourishing among children with ASD.

Project description:BackgroundOne consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene.MethodsIn the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample.ResultsSeveral rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A, and MTNR1B.ConclusionsOur report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.

Dataset Information

Melatonin in Children with Autism Spectrum Disorders: How Does the Evidence Fit Together?

Publications

Melatonin in Children with Autism Spectrum Disorders: How Does the Evidence Fit Together?

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