RELATIONSHIP BETWEEN MORNING BLOOD MELATONIN LEVELS AND SLEEP PROBLEMS IN 5-YEAR-OLD CHILDREN WITH ASD
Authors: Saito *Manabu , Terui Ai , Shimoyama Shuji , Sakamoto Yui , Osato Ayako 
Published: February 2025

Abstract

Background
Melatonin 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).

Aims
The 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.

Method
Among 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.

Results
Regarding sleep problems, the mean score of insomnia/sleep rhythm disorder (p&lt;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&lt;0.05), and a tendency for a positive correlation with morning symptoms (r=0.237, p=0.079).

Discussion
When 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.

References
Mengdi 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