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Front Genet. 2019 Nov 22;10:1042. doi: 10.3389/fgene.2019.01042. eCollection 2019.

Circulating Serum MicroRNAs as Potential Diagnostic Biomarkers of Posttraumatic Stress Disorder: A Pilot Study.

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Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Department of Toxicogenomics, Maastricht University, Maastricht, Netherlands.
College of Medicine and Health, University of Exeter Medical School, Exeter, United Kingdom.
Department of Bioinformatics (BiGCaT), NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.
Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju, South Korea.
UMC Utrecht Brain Center, Department of Psychiatry, Utrecht, Netherlands.
Amsterdam UMC (location VUmc), Department of Anatomy and Neurosciences, Amsterdam, Netherlands.
Amsterdam UMC (location VUmc), Department of Psychiatry, Amsterdam, Netherlands.
Arq, Psychotrauma Research Expert Group, Diemen, Netherlands.
Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands.
Military Mental Healthcare, Netherlands Ministry of Defense, Utrecht, Netherlands.
Department of Psychiatry, New York University School of Medicine, New York, United States.


Posttraumatic 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 microRNAs (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 Prospective Research in Stress-Related Military Operations (PRISMO). Three groups were selected: "susceptible" subjects who developed PTSD after combat exposure, "resilient" subjects without PTSD, and nonexposed control subjects (N = 8 per group). Differential expression analysis revealed 22 differentially expressed miRNAs in PTSD subjects compared to controls and 1 in PTSD subjects compared to resilient individuals (after multiple testing correction and a log2 fold-change cutoff of ≥|1|). Weighted Gene Coexpression Network Analysis (WGCNA) identified a module of coexpressed miRNAs which could distinguish between the three groups. In addition, receiver operating characteristic 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 coexpressed miRNAs. Larger studies are now needed to validate and build upon these preliminary findings.


circulating miRNAs; diagnostic biomarker; posttraumatic stress disorder; susceptibility; trauma

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