Leptin as a biomarker of sleep dysregulation in children with ASD: A drug-free cohort study

Abstract

Objective: Autism spectrum disorder (ASD), typically diagnosed before the age of three, is characterized by deficits in social interaction, communication, and repetitive behaviors. Sleep disturbances are highly prevalent in ASD and have been associated with altered neuroendocrine regulation. Leptin, a hormone involved in metabolic balance and circadian rhythms, has been proposed as a potential biomarker of sleep and neurodevelopmental dysfunction. This study aimed to explore the association between serum leptin levels, sleep habits, and autism symptomatology in a cohort of children with ASD.Materials and methods: A total of 76 medication-naïve children with ASD (mean age: 6.86 ± 1.88; range 4–11 years), defined as no current or previous exposure to psychotropic or sleep-modifying medications (including melatonin, stimulants, antihistamines, antidepressants, and antipsychotics), were compared to 105 age-matched typically developing controls. ASD diagnosis was based on DSM-5 criteria and confirmed using ADOS-2, ADI-R, and SRS-2. Sleep disturbances were assessed using the caregiver-reported Sleep Disturbance Scale for Children (SDSC) and fasting morning blood samples were collected to measure serum leptin levels.Results: Children with ASD showed significantly higher SDSC total scores (p < 0.001) and leptin levels (p <0.001) compared to controls. Significant positive correlations were observed between leptin levels and sleep disturbance scores as well as autism severity measures (all p < 0.001).Conclusions: These findings highlight a significant association between elevated serum leptin levels and both sleep disturbances and autism symptom severity in medication-naïve children with ASD. While causality cannot be inferred, the data support the potential role of leptin as a peripheral correlate of sleep and behavioral dys-regulation in ASD. Further longitudinal studies are warranted to examine leptin's utility as a monitoring biomarker within neurodevelopmental trajectories.