Clinical potential of epigenetic and microRNA biomarkers in PTSD

Molecular studies identifying alterations associated with PTSD have predominantly focused on candidate genes or conducted genome-wide analyses, often encountering issues with replicability. This review aims to identify robust bi-directional epigenetic and microRNA (miRNA) regulators focusing on their functional impacts on post-traumatic stress disorder (PTSD) and their utility in clinical diagnosis, whilst examining knowledge gaps in the existing research. A systematic search was conducted across multiple databases, including Web of Science, Scopus, Global Health (CABI), and PubMed, augmented by grey literature, yielding 3465 potential articles. Ultimately, 92 studies met the inclusion criteria and were analysed to pinpoint significant epigenetic changes with clinically relevant potential in PTSD. The selected studies explored histone modifications, CpG sites, single nucleotide polymorphisms (SNPs), and miRNA biomarkers. Specifically, nine studies examined epigenetic markers, detailing the influence of methylation on chromatin accessibility at histone positions H3K4, H3K9, and H3K36 within a PTSD context. Seventy-three studies investigated DNA methylation, identifying 20 hypermethylated and five hypomethylated CpG islands consistently observed in PTSD participants. Nineteen studies linked 88 SNPs to PTSD, with only one SNP replicated within these studies. Furthermore, sixteen studies focused on miRNAs, with findings indicating 194 downregulated and 24 upregulated miRNAs were associated with PTSD. Although there are epigenetic mechanisms that are significantly affected by PTSD, a granular deconstruction of these mechanisms elucidates the need to incorporate more nuanced approaches to identifying the factors that contribute to PTSD. Technological advances in diagnostic tools are driving the need to integrate detailed participant characteristics, trauma type, genetic susceptibilities, and best practices for robust reporting. This comprehensive approach will be crucial for enhancing the translational potential of PTSD research for clinical application.

既往旨在识别与创伤后应激障碍（Post-Traumatic Stress Disorder，PTSD）相关分子改变的研究，多聚焦于候选基因或开展全基因组分析，且常面临可重复性不足的问题。本综述旨在筛选可靠的双向表观遗传调控因子与微小RNA（microRNA，miRNA），分析其对PTSD的功能影响及临床诊断应用价值，同时梳理当前研究中存在的知识空白。本研究通过Web of Science、Scopus、Global Health (CABI)、PubMed等多个数据库开展系统性检索，并辅以灰色文献，最终得到3465篇潜在相关文献。最终共有92项研究符合纳入标准，本综述对其进行分析，以明确PTSD中具有临床转化潜力的表观遗传改变。纳入的研究涉及组蛋白修饰、CpG位点、单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）以及miRNA生物标志物等方向。具体而言，9项研究针对表观遗传标记展开分析，详细阐述了甲基化对PTSD情境下组蛋白位点H3K4、H3K9及H3K36处染色质开放性的调控作用。73项研究聚焦DNA甲基化，明确了在PTSD患者中反复观测到的20个高甲基化CpG岛与5个低甲基化CpG岛。19项研究将88个SNPs与PTSD相关联，但其中仅1个SNP在研究中得到重复验证。此外，16项研究针对miRNA展开分析，结果显示共有194个表达下调、24个表达上调的miRNA与PTSD存在关联。尽管已有表观遗传机制被证实受PTSD显著调控，但对这些机制的精细化解构表明，亟需采用更为精细的研究方法来识别PTSD的致病相关因素。诊断工具的技术进步推动了研究整合的需求，即需纳入更详尽的受试者特征、创伤类型、遗传易感性等信息，并采用标准化报告规范以保障研究可靠性。这种综合性研究策略对于提升PTSD研究的临床转化潜力至关重要。