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

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.

Conducting actigraphy research in children with neurodevelopmental disorders--a practical approach.

The literature has been highly informative for when to use actigraphy and its validity in pediatric research. However, minimal literature exists on how to perform actigraphy, especially in special populations. We determined whether providing actigraphy training to parents and coordinators increased the nights of actigraphy data that could be scored. We compared two studies in children with autism spectrum disorders, one of which provided a basic level of training in a single-site trial and the other of which provided more detailed training to parents and coordinators in a multisite trial. There was an increase in scorable nights in the multisite trial containing a one-hour structured parent training session. Our results support the use of educational tools in clinical trials that use actigraphy.

Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep.

Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C(max)) and time to peak concentration (T(max)) were comparable to those previously published in the literature for typically developing children, and dim light melatonin onsets were captured in the majority of children. In treatment samples (supplemental melatonin), melatonin parameters were also comparable to those previously published for typically developing children. Our findings support that children with ASD and insomnia responsive to low dose melatonin treatment have relatively normal profiles of endogenous and supplemental melatonin.

Parent-based sleep education for children with autism spectrum disorders.

This study provided sleep education to parents of children with autism spectrum disorder (ASD) to determine whether an individual or group format was more effective in improving sleep and aspects of daytime behavior and family functioning. Eighty children, ages 2-10 years, with ASD and sleep onset delay completed the study. Actigraphy and parent questionnaires were collected at baseline and 1 month after treatment. Mode of education did not affect outcomes. Sleep latency, insomnia subscales on the Children's Sleep Habits Questionnaire, and other outcomes related to child and family functioning improved with treatment. Parent-based sleep education, delivered in relatively few sessions, was associated with improved sleep onset delay in children with ASD. Group versus individualized education did not affect outcome.

Effects of a standardized pamphlet on insomnia in children with autism spectrum disorders.

OBJECTIVE: Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders (ASDs). We determined whether a pamphlet alone could be used by parents to help their child's insomnia. METHODS: Thirty-six children with ASD, ages 2 to 10 years, were enrolled. All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more. Parents were randomly assigned to receive the sleep education pamphlet or no intervention. Children wore an actigraphy device to record baseline sleep parameters, with the primary outcome variable being change in sleep latency. Actigraphy data were collected a second time 2 weeks after the parent received the randomization assignment and analyzed by using Student's t test. Parents were also asked a series of questions to gather information about the pamphlet and its usefulness. RESULTS: Although participants randomized to the 2 arms did not differ statistically in age, gender, socioeconomic status, total Children's Sleep Habits Questionnaire score, or actigraphy parameters, some differences may be large enough to affect results. Mean change in sleep-onset latency did not differ between the randomized groups (pamphlet versus no pamphlet). Parents commented that the pamphlet contained good information, but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice. CONCLUSIONS: A sleep education pamphlet did not appear to improve sleep latency in children with ASDs.

A pilot study of shoulder placement for actigraphy in children.

Children with neurodevelopmental disorders may have difficulty tolerating devices that monitor sleep, presenting challenges in measuring sleep disturbances in this population. Although wrist actigraphy has advantages over polysomnography, some children remain unable to tolerate wrist placement. This study piloted an alternative site for actigraphy in 8 children with autism, ages 6-10 years. Results are presented from the 2 locations (custom pocket shoulder location and wrist location) using Bland-Altman limits of agreement and other statistical measures to compare sleep onset latency, total sleep time, sleep efficiency, and wake after sleep onset. The use of an alternative actigraphy site for children with autism, who have difficulty tolerating actigraphy placement, appears promising and worthy of further study.

Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes.

Supplemental melatonin has shown promise in treating sleep onset insomnia in children with autism spectrum disorders (ASD). Twenty-four children, free of psychotropic medications, completed an open-label dose-escalation study to assess dose-response, tolerability, safety, feasibility of collecting actigraphy data, and ability of outcome measures to detect change during a 14-week intervention. Supplemental melatonin improved sleep latency, as measured by actigraphy, in most children at 1 or 3 mg dosages. It was effective in week 1 of treatment, maintained effects over several months, was well tolerated and safe, and showed improvement in sleep, behavior, and parenting stress. Our findings contribute to the growing literature on supplemental melatonin for insomnia in ASD and inform planning for a large randomized trial in this population.