Álvarez-Mejía Diana, Rodas Jose A, Leon-Rojas Jose E
Cerebro, Emoción y Conducta (CEC) Research Group, Escuela de Medicina, Universidad de las Américas (UDLA), Quito 170125, Ecuador.
School of Psychology, University College Dublin, D04 V1W8 Dublin, Ireland.
Int J Mol Sci. 2025 Jun 25;26(13):6096. doi: 10.3390/ijms26136096.
The intrauterine environment is increasingly recognised as a critical period for the emergence of mental health vulnerabilities. This review explores how adverse maternal exposures, such as psychological stress, infection, malnutrition, and environmental toxins, can disrupt foetal neurodevelopment via epigenetic mechanisms, contributing to the risk of psychiatric and neurodevelopmental disorders. Focusing primarily on human studies, we synthesise evidence on DNA methylation, histone modifications, and non-coding RNAs as key pathways through which the intrauterine environment influences gene regulation in the developing brain. We examine how timing of exposure, foetal sex, and gene-environment interactions modulate these effects, with particular attention to disorders such as schizophrenia, autism spectrum disorder, depression, and anxiety. The placenta emerges as a central mediator, both reflecting and shaping epigenetic changes in response to maternal signals. We also discuss the reversibility of epigenetic marks and highlight emerging interventions, including nutritional supplementation and maternal mental health support, that may buffer or reverse prenatal epigenetic programming. Methodological challenges are addressed, including tissue specificity and causal inference, and future directions are proposed toward integrating epigenetic biomarkers into early risk assessment and precision mental health and psychiatry. This review emphasises the importance of the prenatal period as a window of vulnerability and opportunity for shaping lifelong mental health.
子宫内环境日益被认为是心理健康易感性出现的关键时期。本综述探讨了不良的母体暴露，如心理压力、感染、营养不良和环境毒素，如何通过表观遗传机制扰乱胎儿神经发育，增加患精神疾病和神经发育障碍的风险。主要聚焦于人体研究，我们综合了有关DNA甲基化、组蛋白修饰和非编码RNA的证据，这些是子宫内环境影响发育中大脑基因调控的关键途径。我们研究了暴露时间、胎儿性别和基因-环境相互作用如何调节这些影响，特别关注精神分裂症、自闭症谱系障碍、抑郁症和焦虑症等疾病。胎盘成为一个核心调节因子，既能反映又能塑造对母体信号作出反应的表观遗传变化。我们还讨论了表观遗传标记的可逆性，并强调了新出现的干预措施，包括营养补充和孕产妇心理健康支持，这些措施可能缓冲或逆转产前表观遗传编程。文中探讨了方法学挑战，包括组织特异性和因果推断，并提出了将表观遗传生物标志物纳入早期风险评估以及精准心理健康和精神病学的未来方向。本综述强调了孕期作为塑造终身心理健康的脆弱性和机遇窗口的重要性。
