Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

INTRODUCTION Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that often presents before the child enters the educational system and is characterized by developmental deficits with impairments in three main areas [1] personal, [2] social, and [3] academic or occupational functioning. The neurodevelopmental disorders represent a group of conditions with an onset early in the developmental period. Sleep disorders are commonly reported by parents of children with an ASD diagnosis with between 50% to 80% of parents reporting sleep problems with their children. Problems can be categorized into dyssomnias (problems falling and/or remaining asleep) and parasomnias (abnormal and/or unnatural movements, behaviors, emotions, perceptions, and dreams).

BackgroundMelatonin is one of the neurotransmitters that induces sleep and regulates sleep rhythm. The prevalence of sleep disorders in children with autism spectrum disorder (ASD) is significantly higher than in typically developing children (Chen, 2021). It has been reported that melatonin secretion is abnormal in ASD (Lalanne, 2021).AimsThe purpose of this study was to investigate the relationship between morning blood melatonin levels (mbMEL), ASD diagnosis, and sleep problems in 5-year-old children, and to clarify specific sleep problems that may be targets for melatonin treatment.MethodAmong children who underwent detailed medical examination for 5-year-old children and consented to blood sampling, children who were diagnosed with ASD according to DSM-5 criteria and judged to have Autism or Autism spectrum according to ADOS-2 were classified into the ASD group (n = 46), children whose developmental tests were normal and who were not diagnosed with a neurodevelopmental disorder were classified into the TD group (n = 10). The Japanese Infant Sleep Questionnaire (JSQP) was used to evaluate sleep habits. Blood was collected in the morning on an empty stomach (8:30 AM), and mbMEL was measured using an ELISA kit (arigo). Mann-Whitney U test and Pearson's correlation analysis were used for statistical analysis. This study was approved by the Hirosaki University Graduate School of Health Sciences Ethics Committee.ResultsRegarding sleep problems, the mean score of insomnia/sleep rhythm disorder (p<0.05) was significantly higher in the ASD group. There was no significant difference in the mean value of mbMEL between the two groups. In the entire sample, there was a significant positive correlation between mbMEL and insomnia/sleep rhythm disorder (r=0.289, p<0.05), and a tendency for a positive correlation with morning symptoms (r=0.237, p=0.079).DiscussionWhen compared with the measures of previous studies, the ASD group had more delayed sleep onset, anxiety about falling asleep, resistance to bedtime, and daytime sleepiness, which is consistent with previous studies. The reason why there was no difference in mbMEL between the two groups may be due to the possibility that mbMEL abnormalities are specific to sleep problems rather than ASD diagnosis, or because the sample size was small. All samples showed an association between mbMEL and insomnia, dysrhythmia, and morning symptoms. These findings are consistent with melatonin's role in inducing sleep and regulating sleep rhythm. Children with daytime sleepiness, resistance to bedtime, sleep anxiety, and delayed sleep onset may have a delayed phase of increase/decrease in blood melatonin levels (bMEL), and the amplitude of increase/decrease in bMEL may be small., I believe that supplementing melatonin at night is useful for these conditions.However, in this study, bMEL was not measured at night, so the actual phase and amplitude are unknown. Conclusion: Daytime sleepiness, resistance to bedtime, sleep anxiety, and delayed sleep onset were more common in children with ASD. These results were associated with mbMEL regardless of ASD diagnosis, suggesting that melatonin treatment may be effective.ReferencesMengdi Chen, et al. Sleep problems, attention, and classroom learning behaviors of Chinese elementary school children: The moderating role of gender. School Psychology International 2021, Vol. 42(4)341–357 Sé bastien Lalanne, et al. Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder. Int. J. Mol. Sci. 2021, 22(3), 1490; https://doi.org/10.3390/ijms22031490

Managing insomnia in children with autism spectrum disorder

Purpose - to determine the prevalence of sleep disorders in children with epileptic encephalopathies and autism spectrum disorder (ASD); to evaluate the effectiveness of neuroadaptogenic «Silenta» in the treatment of sleep disorders in children in this group. Materials and methods. We examined 50 children with clinical manifestations of ASD aged 2 to 8 years (mean age was 4.3 years±1.5), including 31 boys and 19 girls. The examination included anamnesis to clarify the features of the pre- and perinatal period, clinical and neurological examination, video EEG monitoring during night sleep for 8 hours, survey of parents on the quality of sleep in children using the Children’s Sleep Habits Questionnaire (CSHQ). All children were divided into 2 groups depending on clinical features: Group 1 - 28 children with ASD who had epileptic seizures at the time of examination or in the anamnesis (children with epileptic encephalopathies); Group 2 - 22 children with ASD without clinical epileptic seizures. Children from the 1st group were prescribed neuroadaptogen «Silenta» for 30 days. Results. Children with ASD and epileptic seizures had higher sub-scales «Difficulty falling asleep», «Parasomnia» and the overall score on the CSHQ-A scale. The results indicate a negative impact of epileptic seizures in children with ASD on sleep quality and the frequency of paroxysmal sleep disorders. The overall prevalence of sleep disorders in children with ASD was determined using the CSHQ-A questionnaire before and after treatment. The incidence of sleep disorders in children with ASD and epileptic seizures after treatment decreased from 85.7% to 53.6%, and in children with ASD without epileptic seizures - from 63.6% to 22.7%. In both groups statistically significant reduction in the proportion of children with sleep disorders after a course of treatment with neuroadaptogen «Silenta». Conclusions. It is shown that the frequency of sleep disorders in children with ASD and epileptic seizures is 85.7%, and in children with ASD without epileptic seizures - 63.6%. In children with ASD and epileptic seizures the incidence of sleep disorders during 30 days of the neuroadaptogen «Silenty» decreased to 53.6%, and in children with ASD and without epileptic seizures the incidence of sleep disorders decreased to 22.7%. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Background: Autism Spectrum Disorder (ASD) includes neurodevelopmental problems throughout life that affect all areas of child development such as abnormal and impaired social interaction, problems in communication, restricted interest, repetitive and stereotypical behaviors. Sleep problems are most commonly complained by parents of children suffering from ASD. About 20-30% of children less than 5 years with normal development give complaints of sleep problems mainly of bedtime resistance, sleep onset delay and night awakening. Less commonly reported sleep disturbance by parents is nightmares or night terrors repetitive and stereotypical behavior. Less frequently reported complain is of breathing sleep disorder. It has already been proved by many studies that ASD children have more complaints about sleep problems than in normal children. But the data of children with ASD having sleep problems in the Indian population is less, so with our study we want to know the prevalence of ASD children with sleep problems in children of the hilly area of Uttarakhand. Objective: The study aims to know the different problems related to sleep faced by children suffering from ASD ( Age range from 4 to 10 years ) with autistic spectrum disorders using the Children’s Sleep Habit Questionnaire (Preschool and school-age, abbreviated version). Subjects and Method s: All patients of ASD presenting to the Psychiatry and Pediatric Outpatient department of Government Medical College and Susheela Tiwari trust Hospital, Haldwani, Uttarakhand from in February 2019 to January 2020. It’s a cross-sectional study of children with different problems related to sleep faced by children suffering from ASD ( Age range from 4 to 10 years ) with autistic spectrum disorders using the Children’s Sleep Habit Questionnaire (CSHQ) (Preschool and school-age, abbreviated version). Results: Demographic and clinical characteristics: The sample consisted of 30 children of ASD with sleep problems ( Mean Age 8.06 years, SD 3.25, Male 21 and Female 9 Children) age range from 4 Years to 10 Years and is compare from 30 normal children (mean age 9.06 Years, SD 3.15, Male 21 and Female 9) for the control group. Both groups were analysed using CSHQ tools. There were no statistically significant differences in age and gender (P value more than 0.05). About 60% (n=18) of the children suffering from ASD had an intellectual disability and 40% (n=12) children with ASD had normal Intellectual. Comparison of Total CSHQ score, bedtime resistance and sleep anxiety showed a statistically significant difference in children suffering from ASD with sleep disorder when compared from normal children. Using CSHQ tools sleep onset delay, night waking, day time sleepiness, parasomnias and sleep –disorder breathing does not show any statistical difference between children with ASD and normal children used as Control. Conclusion: This study compared sleep problems between children with ASD and typically developing children (4-10 Years of age) and examined associated factors of sleep problems in ASD from a different point of view.

Sleep disorders in children with autism spectrum disorders (ASDs) are well-described. However, there is a lack of specific assessment tools to investigate sleep disturbance in this target population. The present investigation reports the Italian validation of the Sleep Disturbance Scale for Children (SDSC) in the ASD population, also investigating the correlation between sleep disorders In both children and parents. Internal consistency and test–retest reliability were investigated using Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively. Concurrent validity was analyzed by comparing the score of the SDSC with the Pittsburgh Sleep Quality Index (PSQI), while the correlation between the SDCS score and the General Sleep Disturbance Scale (GSDS) was used to analyze the correlation between sleep disorders in children and sleep disorders in their parents. In total, 99 children with a diagnosis of ASD participated in the study. Cronbach’s alpha revealed satisfactory value (0.853), as well as reliability (ICC 0.972) and concurrent validity (0.745). Our results also revealed a significant linear correlation between children’s and parents’ sleep disorders (p < 0.05). In conclusion, we found the SDSC to be a useful tool for measuring sleep disorders in ASD children. Our findings offer concrete inputs to achieve adequate pathways for taking care of children with ASDs and their parents.

BackgroundChildren with autism spectrum disorders (ASDs) suffer from sleep disorders to a considerable degree; however, there is no safe and effective treatment available in clinical practice. The objective of the trial is to assess the clinical effectiveness of auricular plaster therapy (APT) in treating sleep disorders in children with ASD.MethodThis is a single-center, patient-assessor blind, randomized controlled trial. A total of 44 preschool children with sleep disorders with ASD will be included in this study. Eligible participants will be randomly assigned to either the auricular plaster group or the sham auricular plaster group in a 1:1 ratio. Participants in the different groups will receive APT or sham APT, respectively, for a total of 30 sessions over 30 days. The primary outcome includes the Children's Sleep Habits Questionnaire (CSHQ), while secondary outcomes include the Autism Behavior Checklist (ABC) and polysomnography (PSG) for total sleep time, sleep latency, awakening duration, and sleep structures. The CSHQ and ABC will be assessed at baseline, 10, 20, 30, 60, 90, and 120 days after randomization, whereas PSG will be assessed at baseline and 30 days after randomization. The follow-up period will be scheduled to be 60, 90, and 120 days after randomization.DiscussionThe results of this study may provide evidence of the efficacy of APT, as well as offer new alternatives for the treatment of sleep disorders in children with ASD.Trial registrationCHiCTR.org.cn (ChiCTR2100048257). Registered on July 5, 2021.

Sleep problems are a common complaint in children/adolescents with autism spectrum disorder (ASD). Correctly diagnosing and treating sleep problems in individuals with ASD is key, as they can add to the psychosocial burden of the disorder and exacerbate associated symptoms, such as inattention or irritability. Here, we provide an overview of the epidemiology, diagnosis, and management of sleep problems/disorders in children and adolescents with ASD. This narrative review is mainly informed by a systematic search in PubMed and PsycInfo (last search: 10 October 2019) of available pertinent meta-analyses. We also searched for randomized controlled trials (RCTs) published after the search date of available meta-analyses. As for the epidemiology of sleep disorders in ASD, recent meta-analytic evidence shows a pooled prevalence of 13% (95% confidence interval [CI] 9-17) in the ASD population, compared with 3.7% in the general population. In terms of diagnosis of sleep disorders, it should be based on standardized criteria [e.g., the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or third edition of the International Classification of Sleep Disorders (ICSD)]; clinicians should bear in mind that the communication difficulties presented by individuals with ASD may make the diagnostic process more challenging. Regarding the treatment, a meta-analysis of behavioral interventions, including only three RCTs, found significant effects in terms of increase in total sleep time (24.41min, 95% CI 5.71-43.11, P = 0.01), decrease in sleep-onset latency (- 18.31min, 95% CI - 30.84 to - 5.77, P = 0.004), and a significant effect on sleep efficiency (5.59, 95% CI 0.87-10.31, P = 0.02), albeit the risk of bias of the included studies was rated "high" in relation to issues with the blinding. The bulk of the evidence for the pharmacological treatment is for melatonin, with a meta-analysis of five double-blind RCTs showing a large effect size, favoring melatonin, in sleep duration (44min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65]) and sleep-onset latency (39min compared with placebo, Hedge's g - 2.46 [95% CI - 1.96 to - 2.98]). We conclude that additional RCTs are desperately needed to support the management of sleep disorders in ASD with an evidence-based, precision medicine approach.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by deficits in social communication and repetitive behaviours, often accompanied by sleep disturbances. These sleep problems, including prolonged sleep latency and fragmented sleep, affect more than half of autistic individuals, exacerbating functional impairments and diminishing quality of life. Cognitive behavioural therapy (CBT) has shown promise in addressing sleep disturbances in ASD, with preliminary studies indicating improvements in sleep quality. However, no systematic review has comprehensively summarised the effects of CBT on sleep in autistic individuals. This systematic review and meta-analysis will synthesise evidence on the efficacy of CBT for improving sleep quality in individuals with ASD. We will search multiple databases (eg, PubMed, Web of Science) for studies published until May 2025. Inclusion criteria encompass randomised controlled trials, single-arm studies and observational studies involving children and adults with ASD and moderate sleep problems. Interventions targeting sleep quality using CBT techniques will be considered. Data extraction will focus on study details, participant information, intervention specifics and sleep outcome measures (eg, total sleep time, sleep onset latency, etc). Risk of bias will be assessed using tools such as Cochrane Risk of Bias Tool V.2, Risk Of Bias In Non-randomised Studies-of Interventions and Review Manager 5.3. A meta-analysis will be conducted using Stata 18, with heterogeneity evaluated using the I² statistic and Cochran's Q test. Given that the dataset for this investigation is derived from publicly accessible databases, there is no direct interaction with patients; thus, ethical approval is not required. CRD42025643701.

Sleep & attention profiles in children with Autism Spectrum Disorder

Can We Predict Which Children With Autism Will Have Obstructive Sleep Apnea?

This study aims to assess the incidence and characteristics of sleep disorders in children and adolescents with Autism Spectrum Disorder (ASD) in Georgia. This research is particularly relevant because ASD is a neurodevelopmental disorder, and one of its most challenging issues is sleep disorders. In Georgia, the number of children and adolescents with ASD has increased significantly over the past two decades, yet sleep disorders among this population have not been studied at all to date. The parents (volunteers) of 500 ASD children/adolescents (without comorbid conditions and medication-free) participated in this study. Children and adolescents with ASD who had sleep disorders were identified based on subjective data collected from their parents using a modified version of the Children's Sleep Habits Questionnaire, as well as the Simonds & Paraga modified version. The control group consisted of typically developing, age-matched peers. Results treated statistically by ANOVA, with Student's t criteria. For the first time, we discovered serious sleep disorders in 61% of Georgian children and adolescents with ASD characterized by: a) difficulties falling asleep, significant increases in sleep latency, and heightened sleep resistance; b) frequent awakenings and challenges in maintaining nighttime sleep; and c) a notable increase in anxiety and nightmares. All of these considerably worsen sleep quality, which can, in turn, have further consequences on the behavioral symptoms of ASD. The results will serve as diagnostic criteria for clinicians to prescribe personalized sleep therapy for each child or adolescent with ASD, in conjunction with behavioral therapy.

Questionnaire Helps Identify Children's Sleep Disorders

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder with deficient social skills, communication deficits and repetitive behaviors. The prevalence of ASD has increased among children in recent years. Children with ASD experience more sleep problems, and sleep appears to be essential for the survival and integrity of most living organisms, especially for typical synaptic development and brain plasticity. Many methods have been used to assess sleep problems over past decades such as sleep diaries and parent-reported questionnaires, electroencephalography, actigraphy and videosomnography. A substantial number of rodent and non-human primate models of ASD have been generated. Many of these animal models exhibited sleep disorders at an early age. The aim of this review is to examine and discuss sleep disorders in children with ASD. Toward this aim, we evaluated the prevalence, clinical characteristics, phenotypic analyses, and pathophysiological brain mechanisms of ASD. We highlight the current state of animal models for ASD and explore their implications and prospects for investigating sleep disorders associated with ASD.

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan