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<p>The global rise in addictive drug use has become a major public health concern, increasingly linked to the development of depression-a psychiatric disorder affecting over 300 million people worldwide. Emerging evidence indicates that chronic exposure to addictive substances can induce or exacerbate depressive symptoms through reward circuitry alterations, neuroinflammation, altered hypothalamic pituitary adrenal axis function, and mitochondrial dysfunction, thereby establishing a neurobiological milieu that favors drug induced depressive states. This review summarizes how epigenetic mechanisms, such as DNA methylation, histone modifications, non-coding RNAs and RNA modifications, convey the enduring effects of addictive drugs on gene expression related to mood regulation, stress response, and neural plasticity, offering potential biomarkers for early detection and individualized treatment. We further outline major technical constraints and unresolved mechanistic issues and highlight emerging approaches such as cell type resolved epigenomic mapping and locus specific epigenome editing that may enable more causal and translational insights. By integrating neurobiological and epigenetic perspectives, this review offers a clearer framework for understanding addiction and depression comorbidity and points to promising therapeutic opportunities.</p>

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Addictive drug abuse and depression-a focus on epigenetics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月21日

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  • Wangwei Zhang,
  • Mingyue Xu,
  • Chong Wang,
  • Hongyue Liang,
  • Xu Zhu,
  • Ying Pan,
  • Feng Guo

摘要

The global rise in addictive drug use has become a major public health concern, increasingly linked to the development of depression-a psychiatric disorder affecting over 300 million people worldwide. Emerging evidence indicates that chronic exposure to addictive substances can induce or exacerbate depressive symptoms through reward circuitry alterations, neuroinflammation, altered hypothalamic pituitary adrenal axis function, and mitochondrial dysfunction, thereby establishing a neurobiological milieu that favors drug induced depressive states. This review summarizes how epigenetic mechanisms, such as DNA methylation, histone modifications, non-coding RNAs and RNA modifications, convey the enduring effects of addictive drugs on gene expression related to mood regulation, stress response, and neural plasticity, offering potential biomarkers for early detection and individualized treatment. We further outline major technical constraints and unresolved mechanistic issues and highlight emerging approaches such as cell type resolved epigenomic mapping and locus specific epigenome editing that may enable more causal and translational insights. By integrating neurobiological and epigenetic perspectives, this review offers a clearer framework for understanding addiction and depression comorbidity and points to promising therapeutic opportunities.