Abstract
In the contemporary research landscape of mental illness treatment, fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges. Although exposure therapy remains a fundamental component of treatment, its efficacy varies considerably among individuals. DNA methylation plays a pivotal role in the extinction of fear memories, providing a promising molecular mechanism that could enhance the success of exposure-based interventions. Extensive studies have consistently demonstrated a substantial association between DNA methylation and neuronal plasticity. While DNA methylation holds potential regulatory effects on the effectiveness of exposure therapy, the bidirectional regulatory relationship between it and neuronal activity necessitates addressing several challenges before its widespread clinical application for mental disorders. First, excessive DNA methylation may suppress neural function, and non-selective enhancement of methylation could be counterproductive. Furthermore, due to potential systemic side effects, the use of methylation-modulating agents might disrupt the physiological balance and functionality of other organs and systems. Despite the dynamic interplay between DNA methylation and neuronal activity offering novel insights into the treatment of mental disorders, the strict consideration of target specificity and an appropriate dosing window requires cautious implementation in clinical practice.