Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
MD/PhD program, Drexel University College of Medicine, Philadelphia, PA, USA.
Mol Psychiatry. 2023 Nov;28(11):4553-4567. doi: 10.1038/s41380-023-02235-4. Epub 2023 Sep 7.
Psychedelic compounds are being increasingly explored as a potential therapeutic option for treating several psychiatric conditions, despite relatively little being known about their mechanism of action. One such possible mechanism, DNA methylation, is a process of epigenetic regulation that changes gene expression via chemical modification of nitrogenous bases. DNA methylation has been implicated in the pathophysiology of several psychiatric conditions, including schizophrenia (SZ) and major depressive disorder (MDD). In this review, we propose alterations to DNA methylation as a converging model for the therapeutic effects of psychedelic compounds, highlighting the N-methyl D-aspartate receptor (NMDAR), a crucial mediator of synaptic plasticity with known dysfunction in both diseases, as an example and anchoring point. We review the established evidence relating aberrant DNA methylation to NMDAR dysfunction in SZ and MDD and provide a model asserting that psychedelic substances may act through an epigenetic mechanism to provide therapeutic effects in the context of these disorders.
迷幻化合物作为治疗几种精神疾病的潜在治疗选择，正越来越受到关注，尽管人们对其作用机制知之甚少。一种可能的机制是 DNA 甲基化，这是一种通过氮碱基的化学修饰来改变基因表达的表观遗传调控过程。DNA 甲基化与几种精神疾病的病理生理学有关，包括精神分裂症 (SZ) 和重度抑郁症 (MDD)。在这篇综述中，我们提出 DNA 甲基化的改变是迷幻化合物治疗效果的一个趋同模型，以 N-甲基-D-天冬氨酸受体 (NMDAR) 为例，强调其作为一个关键的突触可塑性介质，在这两种疾病中都存在功能障碍。我们回顾了与 SZ 和 MDD 中异常的 DNA 甲基化与 NMDAR 功能障碍相关的已确立证据，并提出了一个模型，断言迷幻物质可能通过表观遗传机制在这些疾病的背景下发挥治疗作用。
