Abstract: Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events. Currently, there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder. In addition, the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment. Evidence suggests that this condition is a multisystem disorder that affects many biological systems, raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder. We performed a PubMed search for microRNAs (miRNAs) in post-traumatic stress disorder (PTSD) that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023. These included four studies with whole blood, seven with peripheral blood mononuclear cells, four with plasma extracellular vesicles/ exosomes, and one with serum exosomes. One of these studies had also used whole plasma. Two studies were excluded as they did not involve microRNA biomarkers. Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat, and only two were from recently traumatized adult subjects. In measuring miRNA expression levels, many of the studies had used microarray miRNA analysis, miRNA Seq analysis, or NanoString panels. Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls. The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR3130-5p in whole blood; miR-193a-5p, -7113-5p, -125a, -181c, and -671-5p in peripheral blood mononuclear cells; miR-10b-5p, -203a-3p, -4488, -502-3p, -874-3p, -5100, and -7641 in plasma extracellular vesicles/exosomes; and miR-18a-3p and -7-1-5p in blood plasma. Several important limitations identified in the studies need to be taken into account in future studies. Further studies are warranted with war veterans and recently traumatized children, adolescents, and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

Key words: biomarker, diagnosis, microRNA, peripheral blood mononuclear cells, plasma extracellular vesicles/exosomes, post-traumatic stress disorder, serum exosomes, whole blood, whole plasma