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Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation.

ABSTRACT: Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated.

SUBMITTER: Bam M

PROVIDER: S-EPMC4980621 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation.

Bam Marpe M Yang Xiaoming X Zumbrun Elizabeth E EE Zhong Yin Y Zhou Juhua J Ginsberg Jay P JP Leyden Quinne Q Zhang Jiajia J Nagarkatti Prakash S PS Nagarkatti Mitzi M

Scientific reports 20160811

Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an i ...[more]

PMID: 27510991

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Project description:BackgroundOne-third of veterans returning from the 1990-1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.MethodsSymptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups.ResultsGWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.ConclusionWe conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.

Dataset Information

Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation.

Publications

Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation.

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