Aljabali Alaa A A, Alkaraki Almuthanna, Gammoh Omar, Qnais Esam, Alqudah Abdelrahim, Alshaer Walhan, Mishra Vijay, Mishra Yachana, El-Tanani Mohamed
Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid 21163, Jordan.
Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 21163, Jordan.
Curr Rev Clin Exp Pharmacol. 2025 Sep 1. doi: 10.2174/0127724328381443250825092900.
Treatment-Resistant Depression (TRD) is a complex clinical condition characterized by inadequate response to conventional antidepressant treatments. There is growing evidence that microRNAs (miRNAs) play a role in the underlying pathophysiology of TRD and may offer new avenues for diagnostics and therapy.
A structured literature review of peer-reviewed publications indexed in PubMed, Scopus, and Web of Science was conducted. The search strategy included combinations of keywords such as "treatment- resistant depression," "microRNAs," "biomarkers," and "miRNA-based interventions." Articles were selected based on relevance to miRNA expression patterns in TRD, therapeutic modulation, and their clinical potential.
Dysregulation of several miRNAs-including miR-135a, miR-34a, and miR-155-was consistently observed in patients with TRD. These miRNAs were linked to impaired synaptic plasticity and persistent neuroinflammation. Therapeutic approaches using miRNA mimics or inhibitors showed potential in restoring neurobiological balance and enhancing response to traditional antidepressants. However, delivery system limitations and blood-brain barrier penetration remain significant challenges.
miRNAs appear to play a dual role in TRD, serving both as biomarkers for diagnosis and as targets for novel therapies. Integrating miRNA profiling into clinical workflows could enhance diagnostic precision and guide individualized treatment strategies. Translational barriers, such as delivery specificity and standardization of detection protocols, must be addressed before the widespread clinical application of this technology.
This review highlights miRNAs as promising diagnostic and therapeutic tools in TRD. Continued advancements in delivery systems and validation of biomarker panels may pave the way for their clinical implementation in personalized psychiatry.
难治性抑郁症（TRD）是一种复杂的临床病症，其特征是对传统抗抑郁治疗反应不足。越来越多的证据表明，微小RNA（miRNA）在TRD的潜在病理生理学中发挥作用，并可能为诊断和治疗提供新途径。
对PubMed、Scopus和Web of Science索引的同行评审出版物进行结构化文献综述。搜索策略包括“难治性抑郁症”、“微小RNA”、“生物标志物”和“基于miRNA的干预措施”等关键词组合。根据与TRD中miRNA表达模式、治疗调节及其临床潜力的相关性选择文章。
在TRD患者中持续观察到几种miRNA（包括miR-135a、miR-34a和miR-155）的失调。这些miRNA与突触可塑性受损和持续性神经炎症有关。使用miRNA模拟物或抑制剂的治疗方法在恢复神经生物学平衡和增强对传统抗抑郁药的反应方面显示出潜力。然而，递送系统的局限性和血脑屏障穿透仍然是重大挑战。
miRNA似乎在TRD中发挥双重作用，既是诊断的生物标志物，也是新疗法的靶点。将miRNA谱分析整合到临床工作流程中可以提高诊断精度并指导个性化治疗策略。在该技术广泛临床应用之前，必须解决诸如递送特异性和检测方案标准化等转化障碍。
本综述强调miRNA作为TRD中有前景的诊断和治疗工具。递送系统的持续进步和生物标志物面板的验证可能为其在个性化精神病学中的临床应用铺平道路。
