ASD
Insomnia in Children with ASD:
The Role of Melatonin
The physiological increase in melatonin secretion during the night is well established with a peak around 2am and night-time values are usually at least three times greater than daytime values.
Pineal melatonin production is powerfully suppressed by light acting through the retinohypothalamic tract. In addition to light, and consequently seasonal affects, pineal melatonin secretion can also be influenced by endogenous factors including sex, age, and pubertal stage. The measures 
of melatonin concentration in plasma and saliva, or of the urinary excretion of its predominant metabolite, 6-sulphatoxymelatonin (6-SM), are considered the best peripheral indices of human circadian timing.11
Characteristics of the melatonin rhythm used to define timing of the internal clock.
Figure 1. Adapted from Arendt, J., 201011
Melatonin is of interest in autism due to its role in neurodevelopment and the common occurrence of sleep–wake disturbances. Evidence suggests abnormalities in melatonin production in autism, although studies are small and findings are inconsistent. It remains unclear whether melatonin levels are generally reduced or whether circadian rhythm regulation is disrupted, though some individuals may have significant circadian dysregulation.
Melatonin is of interest in autism due to its apparent role in neurodevelopment, reports of sleep-wake rhythm disturbances in individuals with autism, and its beneficial effects when administered to individuals with autism and sleep problems. In addition, central and peripheral alterations in serotonin in autism have been widely reported and it is noteworthy that melatonin is synthesised in only two steps from serotonin in the pineal gland and the gut.10
Prior studies of melatonin production in ASD were often limited by small sample sizes and were equivocal, but all reported abnormalities in melatonin production. However, given the limitations of the available data, it is not possible to conclude if there is a general decrease in melatonin secretion during the whole 24-h cycle, or if the melatonin circadian rhythm is altered or inverted in ASD.
Figure 2. Adapted from Tordjman S, et al., 201210
Tordjman S, et al., (2012), reported a night and daytime deficit 
in melatonin production in a substantial proportion of individuals with autism (see Figure 2). The authors hypothesised that the 
small intra-individual night-time-daytime differences, and the significant absence of melatonin variation found in autism,
might be a reflection of the lower day and night-time levels, or an indication that there exists a subgroup of individuals
with autism that has a dysregulation of their circadian rhythm,
and more precisely an absence of circadian rhythm.10
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50% to 75% of children with neurodevelopmental or phychiatric comorbidities experience paediatric insomnia
Insomnia in Children with ASD: The Aetiological Role of Melatonin
Slenyto® (paediatric prolonged-release melatonin) for:
- treatment of insomnia in children and adolescents aged 2-18 years with Autism Spectrum Disorder (ASD), and/or neurogenetic disorders with aberrant diurnal melatonin secretion and/or nocturnal awakenings, where sleep hygiene measures have been insufficient
- treatment of insomnia in children and adolescents aged 6-17 years with attention-deficit hyperactivity disorder (ADHD) where sleep hygiene measures have been insufficient
- significant improvements, over baseline, in total sleep time, sleep initiation (latency) and maintenance, child behaviours (externalising), caregivers’ quality of life and resolution of caregiver sleep disturbance
References
- Melke, J. et al. Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry. 2008; 13:90-98
- Tordjman, S. et al., Day and night-time excretion of 6-sulphatoxymelatonin in adolescents and young adults with autistic disorder. Psychoneuroendocrinology. 2012; doi.org/10.1016:1-8
- Arendt, J. Occupational Medicine, Volume 60, Issue 1, January 2010, Pages 10–20. https://academic.oup.com/occmed/article/60/1/10/1439565