Epigenetic changes caused by early life stress in the pathogenesis of depression

Eur J Pharmacol. 2025 Apr 25:177671. doi: 10.1016/j.ejphar.2025.177671. Online ahead of print.ABSTRACTMajor depressive disorder (MDD) is a severe psychiatric disorder with a complex and poorly understood pathogenesis. Epigenetics, a rapidly advancing field of biology, has been implicated in various psychiatric conditions, including schizophrenia, anxiety, substance addiction, and autism. Furthermore, substantial research indicates that epigenetic modifications play a crucial role in the etiology of depression. Early life stress (ELS) refers to adverse experiences occurring during prenatal development (e.g., maternal physical and mental health complications during pregnancy) and/or postnatal life (e.g., abuse, neglect, poverty, parental loss, family conflict, violence, and malnutrition). These early-life adversities can lead to epigenetic modifications, which, in turn, influence key biological processes and contribute to the pathogenesis of MDD. This review provides an overview of the regulatory mechanisms and functions of various epigenetic modifications, including non-coding RNAs, DNA methylation, and histone modifications. We then examine ELS-induced epigenetic alterations and their biological consequences, such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, neurogenesis, and neuroplasticity. Finally, we explore their potential implications for both the pathogenesis and treatment of MDD. We hypothesize that ELS-induced epigenetic changes may serve as biomarkers for MDD diagnosis and offer novel therapeutic targets for its treatment.PMID:40288560 | DOI:10.1016/j.ejphar.2025.177671

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