Ngo Ambrose Loc, Ahmad Christopher M, Gharavi Alkhansari Niki, Nguyen Linda, Zhang Huiping
College of Medicine, Kansas City University, Kansas City, MO, USA.
College of Pharmacy, Western University, Pomona, CA, USA.
Complex Psychiatry. 2025 Mar 3;11(1):12-36. doi: 10.1159/000544912. eCollection 2025 Jan-Dec.
Substance use disorder (SUD) is closely associated with epigenetic modifications that significantly impact mental health outcomes. Alcohol and drug misuse induce widespread changes in the epigenome and transcriptome of the central nervous system, disrupting critical processes such as reward signaling and emotional regulation. These alterations in epigenetic regulation and gene expression often persist even after substance cessation, potentially contributing to the onset or worsening of psychiatric conditions, including schizophrenia, depression, stress, and anxiety.
This review delves into key epigenetic mechanisms underlying SUD and its comorbid psychiatric disorders, with a focus on DNA methylation, histone modifications, and noncoding RNA regulation. Additionally, it examines the influence of environmental and biological factors on the epigenome and evaluates emerging epigenetic-based therapeutic strategies aimed at treating SUD and related psychiatric conditions.
Gaining a deeper understanding of the epigenetic mechanisms driving SUD and its associated psychiatric disorders is crucial for the development of effective therapeutic interventions. This review highlights the potential of epigenetic-based pharmacological strategies to mitigate the societal and personal burdens linked to SUD and its mental health complications.
物质使用障碍(SUD)与表观遗传修饰密切相关,表观遗传修饰会显著影响心理健康结果。酒精和药物滥用会引起中枢神经系统表观基因组和转录组的广泛变化,扰乱诸如奖励信号传导和情绪调节等关键过程。即使在停止使用物质后,这些表观遗传调控和基因表达的改变通常仍会持续,这可能导致包括精神分裂症、抑郁症、应激和焦虑症在内的精神疾病的发作或恶化。
本综述深入探讨了物质使用障碍及其共病精神疾病背后的关键表观遗传机制,重点关注DNA甲基化、组蛋白修饰和非编码RNA调控。此外,它还研究了环境和生物学因素对表观基因组的影响,并评估了旨在治疗物质使用障碍及相关精神疾病的新兴表观遗传学治疗策略。
深入了解驱动物质使用障碍及其相关精神疾病的表观遗传机制对于开发有效的治疗干预措施至关重要。本综述强调了基于表观遗传学的药理学策略减轻与物质使用障碍及其心理健康并发症相关的社会和个人负担的潜力。