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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01042

Circulating serum microRNAs as potential diagnostic biomarkers of post-traumatic stress disorder: A pilot study

 Clara Snijders1, Julian Krauskopf2, Ehsan Pishva1, 3,  Lars Eijssen1, 4, Barbie Machiels1, Jos Kleinjans2,  Gunter Kenis1,  Daniel van den Hove1,  Myeong Ok Kim5, Marco P. Boks6,  Christiaan H. Vinkers7, 8, Eric Vermetten9, 10, 11, 12, Elbert Geuze6, 12,  Bart P. Rutten1 and  Laurence De Nijs1*
  • 1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Netherlands
  • 2Department of Toxicogenomics, Maastricht University, Netherlands
  • 3College of Medicine and Health, University of Exeter, United Kingdom
  • 4Department of Bioinformatics (BiGCaT), Maastricht University, Netherlands
  • 5College of Natural Sciences, Division of Applied Life Science, Gyeongsang National Univeristy, South Korea
  • 6Department of Psychiatry, University Medical Center Utrecht, Netherlands
  • 7Department of Anatomy & Neurosciences, VU University Medical Center, Netherlands
  • 8Department of Psychiatry, Medical Center, VU University Amsterdam, Netherlands
  • 9Arq Psychotrauma Expert Group, Netherlands
  • 10Department of Psychiatry, Leiden University Medical Center, Netherlands
  • 11Department of Psychiatry, School of Medicine, New York University, United States
  • 12Ministry of Defence (Netherlands), Netherlands

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop upon exposure to a traumatic event. While most people are able to recover promptly, others are at increased risk of developing PTSD. However, the exact underlying biological mechanisms of differential susceptibility are unknown. Identifying biomarkers of PTSD could assist in its diagnosis and facilitate treatment planning. Here, we identified serum miRNAs of subjects that underwent a traumatic event and aimed to assess their potential to serve as diagnostic biomarkers of PTSD. Next generation sequencing was performed to examine circulating miRNA profiles of 24 members belonging to the Dutch military cohort PRISMO. Three groups were selected: “susceptible” subjects who developed PTSD after combat exposure, “resilient” subjects without PTSD, and non-exposed control subjects (N=8 per group). Differential expression analysis revealed 123 differentially expressed miRNAs in PTSD subjects compared to controls, and 4 in PTSD subjects compared to resilient individuals (after multiple testing correction and a log2 FC cut off of ≥ |1|). Weighted Gene Co-expression Network Analysis (WGCNA) identified a module of co-expressed miRNAs which could distinguish between the three groups. In addition, Receiver Operating Characteristic (ROC) curve analyses suggest that the miRNAs with the highest module memberships could have a strong diagnostic accuracy as reflected by high areas under the curves. Overall, the results of our pilot study suggest that serum miRNAs could potentially serve as diagnostic biomarkers of PTSD, both individually or grouped within a cluster of co-expressed miRNAs. Larger studies are now needed to validate and build upon these preliminary findings.

Keywords: Post-traumatic stress disorder, circulating miRNAs, Diagnostic biomarker, Trauma, susceptibility

Received: 29 Jul 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Snijders, Krauskopf, Pishva, Eijssen, Machiels, Kleinjans, Kenis, van den Hove, Kim, Boks, Vinkers, Vermetten, Geuze, Rutten and De Nijs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Laurence De Nijs, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6226 NB, Netherlands, Laurence.denijs@maastrichtuniversity.nl