Oxysterol Metabolism Balance as a Candidate Biomarker in Autism Spectrum Disorder

The aim of this study was to investigate the role of cholesterol metabolism disorders in the etiopathogenesis of Autism Spectrum Disorder (ASD) through the analysis of central and peripheral oxysterol levels (24-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol). These compounds, found in the cholesterol excretion pathways, are considered potential biomarkers for diagnosing and monitoring various neuropsychiatric disorders.

This study included 42 children diagnosed with ASD, aged between 1 and 6 years, who had no additional psychiatric or medical illnesses other than cognitive delay/intellectual disability and were not on medication, along with 38 age-matched typically developing children. After comprehensive mental health assessments, the symptom severity in children with ASD was evaluated using the Childhood Autism Rating Scale, Autism Behavior Checklist, and Repetitive Behavior Scale-Revised Form. After the clinical evaluation, peripheral blood samples were obtained from all children. Oxysterol levels were assessed using liquid chromatography coupled with tandem mass spectrometry.

In the ASD group, levels of 24-hydroxycholesterol and 25-hydroxycholesterol were significantly higher compared to the control group, while 27-R-hydroxycholesterol levels were lower. The ratio of 24-hydroxycholesterol (μg/L) to 27-hydroxycholesterol (μg/L) was notably higher in the autism group. The receiver operating characteristic (ROC) analysis indicated that this ratio was statistically significant and could discriminate between ASD and non-ASD diagnoses with "acceptable discrimination potential."

Our findings suggest that alterations in oxysterol levels, commonly associated with neurodegenerative processes, can also be observed in ASD and may serve as a potential candidate biomarker for the disorder.