Alahmad Rasheed, Hinchey Liza M, Shaikh Manahil, Amirsadri Alireza, Javanbakht Arash
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Service Dr., Detroit, MI 48201, USA.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Service Dr., Detroit, MI 48201, USA.
J Psychiatr Res. 2025 Feb;182:438-451. doi: 10.1016/j.jpsychires.2025.01.032. Epub 2025 Jan 23.
Police, firefighters, dispatchers, and emergency medical technicians-collectively known as first responders-are a unique population frequently exposed to chronic, traumatic incidents. This exposure results in a high prevalence of PTSD, depression, and anxiety, posing a substantial public health concern. Genetic predispositions and epigenetic modifications that regulate gene expression are significant contributors to trauma-related pathologies. This systematic review aims to summarize current data on epigenetic and gene expression changes in first responders related to three post-trauma pathologies: PTSD, depression, and anxiety. We also explore genetic pathways across these disorders to identify potential commonalities and therapeutic targets.
Following PRISMA guidelines, databases were searched from July to October 2023, yielding 1103 studies, 12 of which met the inclusion criteria (total N = 6943).
Of the included studies, 11 examined PTSD, consistently implicating stress-response genes, such as those in the hypothalamic-pituitary-adrenal axis (e.g., FKBP5, NR3C1), and genes related to inflammation and immune responses. Three studies focused on depression-related genetic biomarkers but reported no significant genome-wide methylation differences between responders with current versus no major depressive disorder (MDD). No studies addressed epigenetic or gene expression changes linked to anxiety.
This review identified novel genes and pathways related to trauma as potential targets for future research and pharmacological therapy. It also highlights a significant gap in the literature, emphasizing the need for broader research to investigate the genetic underpinnings of trauma exposure in first responders, aiming to identify relevant pathways and therapeutic targets.
警察、消防员、调度员和急救医疗技术人员——统称为急救人员——是一个独特的群体,经常暴露于慢性创伤事件中。这种暴露导致创伤后应激障碍(PTSD)、抑郁症和焦虑症的高发病率,构成了重大的公共卫生问题。调节基因表达的遗传易感性和表观遗传修饰是创伤相关病理的重要促成因素。本系统综述旨在总结急救人员中与三种创伤后病理相关的表观遗传和基因表达变化的现有数据:创伤后应激障碍、抑郁症和焦虑症。我们还探索这些疾病的遗传途径,以确定潜在的共性和治疗靶点。
按照PRISMA指南,于2023年7月至10月对数据库进行检索,共获得1103项研究,其中12项符合纳入标准(总样本量N = 6943)。
在纳入的研究中,11项研究考察了创伤后应激障碍,一致涉及应激反应基因,如下丘脑-垂体-肾上腺轴中的基因(如FKBP5、NR3C1)以及与炎症和免疫反应相关的基因。三项研究聚焦于与抑郁症相关的遗传生物标志物,但报告显示,目前患有与未患有重度抑郁症(MDD)的急救人员之间,全基因组甲基化无显著差异。没有研究涉及与焦虑相关的表观遗传或基因表达变化。
本综述确定了与创伤相关的新基因和途径,作为未来研究和药物治疗的潜在靶点。它还突出了文献中的一个重大空白,强调需要进行更广泛的研究,以调查急救人员创伤暴露的遗传基础,旨在确定相关途径和治疗靶点。