Editors' ChoicePosttraumatic Stress Disorder

Genomics are CReePing up on inflammation in PTSD

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Science Translational Medicine  27 Sep 2017:
Vol. 9, Issue 409, eaao6887
DOI: 10.1126/scitranslmed.aao6887


Posttraumatic stress disorder is linked to increased blood and genetic and epigenetic markers of C-reactive protein.

Emerging data link posttraumatic stress disorder (PTSD) to increased levels of systemic inflammation, including heightened peripheral concentrations of C-reactive protein (CRP). However, the contribution of genetic and epigenetic factors that may influence concentrations of CRP in PTSD remains unknown. CRP is encoded by the CRP gene, and recent data highlight associations between single nucleotide polymorphisms (SNP) within the CRP gene, CRP concentrations, and PTSD. Moreover, DNA methylation in the Absent in Myeloma 2 (AIM2) gene, that encodes for the AIM2 protein involved in immune response, has recently been linked to CRP levels. Miller and colleagues designed a study to characterize the effects of SNPs and DNA methylation within the CRP and AIM2 genes on CRP concentrations and PTSD symptoms severity in a group of 286 post-9/11 military veterans.

The results of the study show that CRP concentrations positively correlated with PTSD symptom severity in this cohort and that this relationship was mediated by DNA methylation at a specific locus within AIM2. Analysis of the relationship between SNPs in the CRP gene and PTSD revealed that a functional SNP in the CRP promoter moderated the association between trauma exposure and PTSD symptom severity and that two other SNPs in the CRP gene interacted with PTSD to influence CRP concentrations. Overall, the data indicate that genomic factors contribute to increased inflammation in PTSD. Unfortunately, due to the cross-sectional nature of the study, the exact relationship between genomic factors, inflammation, and PTSD development and severity cannot be determined. Although future longitudinal studies are necessary to pinpoint the exact role of inflammation in the pathophysiology and maintenance of PTSD across military and civilian cohorts, these findings suggest a genetic and epigenetic mechanism by which trauma and PTSD may facilitate the emergence of a proinflammatory state, which increases risk for adverse cardiometabolic outcomes that are highly comorbid with PTSD. Because inflammatory signals may contribute to PTSD symptom severity via their actions on central neurotransmitter systems, the data from Miller and collaborators corroborate previous reports suggesting that antiinflammatory interventions may alleviate PTSD symptoms in traumatized individuals.

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