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Review
. 2025 Mar 3;11(1):12-36.
doi: 10.1159/000544912. eCollection 2025 Jan-Dec.

Epigenetic Insights into Substance Use Disorder and Associated Psychiatric Conditions

Ambrose Loc Ngo  1 , Christopher M Ahmad  1 , Niki Gharavi Alkhansari  1 , Linda Nguyen  2 , Huiping Zhang  3   4
Affiliations
Review

Epigenetic Insights into Substance Use Disorder and Associated Psychiatric Conditions

Ambrose Loc Ngo et al. Complex Psychiatry. .

Abstract

Background: 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.

Summary: 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.

Key messages: 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.

Keywords: Comorbidity; Epigenetics; Psychiatric conditions; Substance use disorder.

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Conflict of interest statement

Dr. Huiping Zhang is a board member of Complex Psychiatry.

Figures

Fig. 1.
Fig. 1.
Substance abuse progresses to mental health issues via epigenetic mechanisms.
See this image and copyright information in PMC

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