Advances in melatonin research in autism spectrum disorders: literature review and new perspectives. In addition, mutations that alter the functional properties of melatonin receptors have been found in individuals with ASD. Finally, beneficial effects of melatonin when administered to individuals with autism and sleep problems have been reported and reinforce the interest in studying melatonin in autism [78-80].
A meta-analysis of placebo-controlled randomized trials of melatonin in individuals with intellectual disabilities and sleep problems. The authors suggest that future research on the efficacy of melatonin in children with ASD should include daytime functioning as a primary outcome measure. The authors reviewed 17 studies on the efficacy and side effects of melatonin in patients with AD, AS, PDD-NOS, and Rett syndrome.
Half of the children had Smith-Magenis syndrome, which involves specific abnormalities of melatonin secretion. Disord A general brief discussion of melatonin and its potential for treating sleep problems in autism. A number of case studies and therapeutic trials of melatonin focused on individuals with developmental disabilities and sleep problems have been reported.
Although the potential therapeutic use of melatonin for sleep problems in autism has been considered for many years [108], available data in large samples of children with autistic disorder are very limited (see Table 2).
Relationships between Melatonin and Autistic Behavioral Impairments
Furthermore, Nir and colleagues [65] presented data suggesting reduced melatonin production in individuals with autism and speech difficulties or EEG abnormalities. Finally, the lower average melatonin production, the significantly smaller day-night differences, and the significantly higher frequency of lack of circadian variation observed in individuals with autism compared to controls may play a role or be a reflection of hypothesized time. problems in "biological clocks" in autism [120,121]. Melatonin administration was reported in two studies [90,92] to improve social withdrawal in children with ASD.
Thus, many studies have referred to the difficulties observed in children with autism in imitating other people's faces, gestures or voice signals to better understand their problems with social interaction and speech development. Further research is desired to explore the development of children with autism in terms of their ability to adapt their own rhythm to an external rhythm. Against this background, it is noteworthy that melatonin levels have been reported to be low in individuals with autism and negatively correlated with the difficulty of verbal communication and social imitative play disorders.
A third hypothesis is that melatonin treatment may increase the perception of rhythms in children with autism. Conversely, based on clinical observations in autism, we can say that children with autism create breaks from continuity. The irregular, if not arrhythmic, circadian rhythms reported in some individuals with autism suggest that the development of children with autism is not based on regularly recurring physiological interruptions, but on anarchic interruptions and even, in many cases, on one.
Abnormally low daytime and nighttime melatonin secretion has been associated with an absence of melatonin circadian variation in individuals with autism which in turn, given the synchronizer role of melatonin, also has consequences for the circadian rhythm network. related to the difficulties in adapting to changes associated with repetitive and restricted interests typically observed in individuals with autism. We can therefore hypothesize that children with autism who are faced with physiological continuity due to absent circadian rhythms have difficulty adapting to changes in either their external or their internal environment. This difficulty in children with autism to adapt to change is also observed in relation to changes in the rhythm of environmental stimuli.
Notably, subjects with autism and seizures tended to have an abnormal melatonin rhythm correlated with EEG changes [65]. Patients with autism are particularly sensitive not only to changes in the rhythm of the external environment, but also to changes occurring in their internal environment. Thus, some female adolescents with autism experience epileptic seizures around the 14th day of their menstrual cycle, which is when the level of luteinizing hormone (LH) peaks.
Conclusions
We end up with a chain of events where a change in rhythm associated with excessive environmental stimuli would increase arousal and induce physiological stress, which in turn would lead to an epileptic seizure for some children with autism. We are currently conducting a therapeutic trial studying the melatonin dose-effect relationship in 32 male children with autistic disorder (Clinical Trials.Gov.: NCT01780883, ANSM A main objective of this randomized, double-blind, placebo-controlled trial is to assess the melatonin effect on the severity of behavioral autistic impairments The roles of melatonin and light in the pathophysiology and treatment of circadian sleep disorders.
Generation of the endocrine melatonin message in mammals: A review of the complex regulation of melatonin synthesis by norepinephrine, peptides and other pineal transmitters. Long-term effects of melatonin on quality of life and sleep in hemodialysis patients (Melodi Study): A randomized controlled trial. The utility of melatonin for developmental sleep and emotional/behavioral disorders – studies of the melatonin trial in 50 patients with developmental disorders.
An open-label study of controlled-release melatonin in the treatment of sleep disorders in children with autism. A randomized, placebo-controlled trial of controlled-release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. Efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome.
Melatonin versus placebo in non-behavioral children with autism spectrum disorders and severe sleep problems. Controlled-release melatonin, alone and in combination with cognitive behavioral therapy, for persistent insomnia in children with autism spectrum disorders: a randomized, placebo-controlled trial. Melatonin for sleep problems in children with neurodevelopmental disorders: a randomized double-masked placebo-controlled trial.
Meta-analysis of the effectiveness of melatonin for sleep-disordered individuals with autism spectrum disorders: should Rett syndrome be included? Melatonin therapy for circadian rhythm sleep disorders in children with multiple disabilities: what we have learned in the past decade.
