2025, Vol. 5, Issue 2, Part B

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent challenges in social communication, repetitive behaviors, and restricted interests. Despite the strong heritability observed in ASD, genetic factors alone do not fully explain the disorder’s heterogeneous nature and the rising prevalence in global populations. Epigenetics, which refers to heritable changes in gene expression that do not involve alterations in the DNA sequence itself, has emerged as a critical framework for understanding ASD. This paper explores the role of epigenetic mechanisms in the pathogenesis of ASD, with a focus on DNA methylation, histone modifications, non-coding RNAs, and gene-environment interactions.
Recent studies have identified key epigenetic alterations in genes critical to neurodevelopment, such as OXTR (oxytocin receptor), SHANK3 (a synaptic scaffolding protein), and MECP2 (methyl-CpG binding protein 2). DNA methylation changes in these and other genes have been observed in individuals with ASD, indicating a potential mechanism through which environmental factors may influence ASD onset and progression. The role of prenatal and perinatal factors, such as maternal immune activation, stress, and exposure to environmental toxins, in mediating epigenetic changes that predispose individuals to ASD is also critically examined. Additionally, advances in high-throughput sequencing technologies, including whole-genome bisulfite sequencing and single-cell RNA-seq, have enabled a deeper understanding of the epigenetic landscape of ASD, allowing for the identification of novel biomarkers and therapeutic targets.
Despite the significant strides in understanding the epigenetic underpinnings of ASD, numerous challenges remain. The field grapples with the complexity of epigenetic regulation, the need for more reproducible studies, and the difficulty of translating findings into clinical applications. This review concludes by emphasizing the need for large-scale, longitudinal studies to further elucidate the causal relationship between epigenetic modifications and ASD. It also calls for the integration of multi-omics approaches and machine learning to enhance our understanding and improve diagnostic and therapeutic strategies for ASD.