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Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder

Institute for Systems Biology, Seattle, WA 98109, USA
Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury, Department of Psychiatry, New York University, New York, NY 10003, USA
Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
James J. Peters VA Medical Center, The Bronx, NY 10468, USA
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD 21702, USA
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(7), 963;
Received: 10 May 2019 / Revised: 26 June 2019 / Accepted: 2 July 2019 / Published: 3 July 2019
(This article belongs to the Section Molecular Medicine)
PDF [1642 KB, uploaded 3 July 2019]


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. View Full-Text
Keywords: post-traumatic stress disorder; microRNA; next-generation sequencing; plasma; extracellular vesicles post-traumatic stress disorder; microRNA; next-generation sequencing; plasma; extracellular vesicles

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Lee, M.Y.; Baxter, D.; Scherler, K.; Kim, T.-K.; Wu, X.; Abu-Amara, D.; Flory, J.; Yehuda, R.; Marmar, C.; Jett, M.; Lee, I.; Wang, K.; Hood, L. Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder. J. Clin. Med. 2019, 8, 963.

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