DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.
Molecular psychiatry – November 01, 2023
Source: PubMed
Summary
Psychedelic compounds may offer therapeutic benefits for psychiatric conditions by influencing DNA methylation, a process that alters gene expression. In a review focusing on schizophrenia and major depressive disorder, evidence shows that 30% of individuals with these conditions exhibit aberrant DNA methylation linked to N-methyl D-aspartate receptor dysfunction. By proposing that psychedelics could reverse these methylation changes, this model highlights a promising epigenetic mechanism that could enhance treatment outcomes for those suffering from these complex disorders.
Abstract
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.