Abstract
Dysregulation of circulating microRNAs (miRNAs) in body fluids has been reported in psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and post-traumatic stress disorder (PTSD). Recent studies of various diseases showed that extracellular vesicles (EV) in body fluids can provide different spectra of circulating miRNAs and disease-associated signatures from whole fluid or EV-depleted fraction. However, the association of miRNAs in EVs to PTSD has not been studied. In this study, we performed a comprehensive profiling of miRNAs in whole plasma, extracellular vesicles (EV) and EV-depleted plasma (EVD) samples collected from combat veterans with PTSD and matched controls by utilizing a next-generation sequencing (NGS) platform. In total, 520 circulating miRNAs were quantified from 24 male Iraq and Afghanistan combat veterans with (n = 12) and without (n = 12) PTSD. The overall miRNA profiles in whole plasma, EV and EVD fractions were different and miRNAs affected by PTSD were also distinct in each sample type. The concentration changes of miR-203a-3p in EV and miR-339-5p in EVD were confirmed in an independent validation cohort that consisted of 20 veterans (10 with and 10 without PTSD) using qPCR. The target genes of these two miRNAs were involved in signaling pathways and comorbid conditions associated with PTSD (e.g., neurotransmitter systems such as dopaminergic and serotonergic signaling, inflammatory response, and cardiovascular diseases). Our findings suggest that PTSD may have different impacts on miRNAs encapsulated in vesicles and outside of vesicles. Further studies using larger samples are needed to evaluate the utility of these miRNAs as diagnostic biomarkers for PTSD.
Highlights
Post-traumatic stress disorder (PTSD) poses a significant burden on emotional and physical health and health care costs [1,2]
Using a social defeat mouse PTSD model, we previously proposed miR-29 as one of the key regulators involved in PTSD associated heart pathologies by modulating extracellular matrix remodeling genes [31]
Our analysis revealed that miR-203a-3p regulates genes involved in the neurotransmitter system, neural development, and immune response which have been reported as being altered in PTSD [60,61,62,63]
Summary
Post-traumatic stress disorder (PTSD) poses a significant burden on emotional and physical health and health care costs [1,2]. The annual treatment cost for PTSD among service members is estimated to be approximately $1.6 billion [6]. Emerging data suggests that this condition is a multisystem disorder affecting many biological systems including cardiovascular, liver metabolism, and immune system [1], raising the possibility that peripheral markers of illness may have utility in establishing the diagnosis of PTSD. Heterogeneity in clinical presentations of PTSD and overlapping symptoms with other conditions, such as traumatic brain injury and major depressive disorder, may mislead diagnosis and result in inappropriate treatment [9,10,11]. Objective biomarkers that can facilitate the process of diagnosing and differentiating PTSD are needed
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