Laboratorio de Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN, CONICET, Buenos Aires, Argentina.
Biochem J. 2024 May 22;481(10):615-642. doi: 10.1042/BCJ20230306.
Early-life adversities, whether prenatal or postnatal exposure, have been linked to adverse mental health outcomes later in life increasing the risk of several psychiatric disorders. Research on its neurobiological consequences demonstrated an association between exposure to adversities and persistent alterations in the structure, function, and connectivity of the brain. Consistent evidence supports the idea that regulation of gene expression through epigenetic mechanisms are involved in embedding the impact of early-life experiences in the genome and mediate between social environments and later behavioral phenotypes. In addition, studies from rodent models and humans suggest that these experiences and the acquired risk factors can be transmitted through epigenetic mechanisms to offspring and the following generations potentially contributing to a cycle of disease or disease risk. However, one of the important aspects of epigenetic mechanisms, unlike genetic sequences that are fixed and unchangeable, is that although the epigenetic markings are long-lasting, they are nevertheless potentially reversible. In this review, we summarize our current understanding of the epigenetic mechanisms involved in the mental health consequences derived from early-life exposure to malnutrition, maltreatment and poverty, adversities with huge and pervasive impact on mental health. We also discuss the evidence about transgenerational epigenetic inheritance in mammals and experimental data suggesting that suitable social and pharmacological interventions could reverse adverse epigenetic modifications induced by early-life negative social experiences. In this regard, these studies must be accompanied by efforts to determine the causes that promote these adversities and that result in health inequity in the population.
早期生活逆境，无论是产前还是产后暴露，都与晚年不良心理健康结局相关，增加了几种精神障碍的风险。对其神经生物学后果的研究表明，逆境暴露与大脑结构、功能和连接的持续改变之间存在关联。一致的证据支持这样一种观点，即通过表观遗传机制调节基因表达参与将早期生活经历嵌入基因组，并在社会环境和后期行为表型之间进行调解。此外，来自啮齿动物模型和人类的研究表明，这些经历和获得的风险因素可以通过表观遗传机制传递给后代和后代，可能导致疾病或疾病风险的循环。然而，与固定且不可改变的遗传序列不同，表观遗传机制的一个重要方面是，尽管表观遗传标记持久存在，但它们仍然具有潜在的可逆性。在这篇综述中，我们总结了我们目前对与早期生活中营养不良、虐待和贫困暴露相关的心理健康后果有关的表观遗传机制的理解，这些逆境对心理健康有巨大而普遍的影响。我们还讨论了关于哺乳动物跨代表观遗传遗传的证据，以及表明适当的社会和药物干预可以逆转早期负面社会经历引起的不良表观遗传修饰的实验数据。在这方面，这些研究必须伴随着努力确定促进这些逆境并导致人群中健康不平等的原因。
