Unlocking the complex interplay between epigenetics and epitranscriptomics in neuropsychiatric disorders

Epigenetic and epitranscriptomic mechanisms work together to control gene expression, which is essential for brain development, synaptic plasticity, and the risk of neuropsychiatric disorders. Traditional epigenetic processes, such as DNA methylation and histone modifications, alter chromatin structure to regulate gene accessibility. On the other hand, epitranscriptomic marks such as N6-methyladenosine (m6A) affect RNA metabolism after transcription. Studies in both neural and non-neural systems show that these layers of regulation interact in both directions and together shape gene expression. This review looks at how m6A-modified non-coding RNAs, including chromosome-associated regulatory RNAs (carRNAs), enhancer RNAs (eRNAs), microRNAs, and circular RNAs, work with chromatin to influence genome function, including chromatin accessibility, histone modifications, and the overall structure of the genome. It also covers recent discoveries about how eRNAs form R-loops, how m6A affects RNA stability, and how these processes are involved in neuronal signaling and plasticity. Many of these findings come from studies outside the nervous system and need more research in neuropsychiatric disease models. By bringing together established knowledge and new ideas, this review suggests that the interaction between epigenetic and epitranscriptomic mechanisms is a key factor in determining risk and resilience for neuropsychiatric disorders, and offers new directions for future research and therapy development.