Sleep Problems and 6-Sulfatoxymelatonin as Possible Predictors of Symptom Severity, Adaptive and Maladaptive Behavior in Children with Autism Spectrum Disorder

Abstract

In children with autism spectrum disorder (ASD), sleep disturbances are a frequent comorbidity with an adverse effect on their behavior and functioning. It was suggested that melatonin deficit is at least partly responsible for the sleep problems. The study aimed to investigate, in a sample of 56 children with ASD aged 2.8–13.3 years, if the sleep problems and melatonin secretion can serve as predictors of adaptive functioning and severity of the ASD core symptoms. We demonstrated that, after adjustment for age, the Sleep score assessed by the Children’s Sleep Habits Questionnaire predicts the Adaptive behavior composite score only in children younger than 6 years, and the preferred predictive model is for the domain Socialization. The age-adjusted Sleep score predicted Externalizing and Internalizing maladaptive behavior, with a near-zero contribution of age to the relationship between the Internalizing maladaptive behavior and Sleep score. After adjustment for age, the reduced night-time melatonin secretion predicted a higher severity of ASD symptoms in the domain Social affect and the Calibrated Severity Score, but not the sleep problems. Our results emphasize the importance of assessing sleep problems as a modifiable predictor of behavior in children with ASD and support the hypothesis about the role of melatonin in pathophysiology of ASD.

The circadian system: A neglected player in neurodevelopmental disorders

“…In line, Tordjman et al (2005) showed that nocturnal levels of 6-sulphatoxymelatonin (6-SM), a urinary melatonin metabolite closely correlated to pineal melatonin secretion, were negatively correlated to ASD symptom severity (deficits in verbal communication and play), a set of findings later replicated by the group (Tordjman et al, 2012). Subsequent studies exploring the predictive power of 6-SM on ASD symptom severity report varying results, where Babinska et al (2019) described no correlation between nocturnal 6-SM secretion and symptom severity, whereas Bartakovicova et al (2022) corroborated the results from Tordjman et al's study by finding a negative correlation between 6-SM secretion levels and symptom severity, after adjusting for age (Figure 3). Thus, these studies suggest that disrupted circadian rhythms, specifically through abnormal melatonin circadian function, may have an impact on ASD pathogenesis.…”

Is Autism a PIN1 Deficiency Syndrome? A Proposed Etiological Role for Glyphosate

“…Melatonin is enzymatically degraded in the liver to 6-hydroxymelatonin and excreted in the urine as 6-sulfatoxymelatonin [32]. Several studies have shown that nocturnal levels of 6-sulfatoxymelatonin are significantly reduced in association with autism [33,34], likely due to impaired melatonin synthesis in the pineal gland. Melatonin is synthesized in the pineal gland from serotonin, through the addition of both an acetyl group and a methyl group.…”

Alterations in Antioxidant Status and Erythrocyte Properties in Children with Autism Spectrum Disorder

“…ASD is characterized by core symptoms that include problems in social communication and interaction, as well as restricted repetitive patterns of behavior, activities or interests [3]. In addition to these behavioral characteristics, children with ASD typically suffer from a wide range of somatic problems at a higher rate than their neurotypical counterparts, e.g., feeding and gastrointestinal disorders [4,5], immunological disturbances [6], sleep disorders [7], neurological diseases and a variety of others [8,9]. Oxidative stress, implicated in the pathophysiology of multiple disorders, has been shown to be a common denominator of neurodevelopmental diseases including ASD [10][11][12].…”