Epigenetic Methylation in PTSD as Moderated by Trauma Exposure in Refugees

Abstract

War-related trauma has adverse effects on refugee mental health and has been implicated in the dysregulation of multiple systems of the body. Trauma can alter genes associated in these systems, contributing to PTSD symptoms via DNA methylation. While there are exceptions, hypermethylation in regulatory regions of genes are associated with poor mental health, e.g., PTSD. The present study examines differential DNA methylation in an HPA axis associated gene in comparison utilizing three groups: those with high levels of trauma and PTSD symptom scores (HH) (n=24), those reporting high levels of trauma but low PTSD symptom scores (HL) (n=14), and those with low levels of trauma and high PTSD scores (LH) (n=10). HH group was used as a reference. Self-report questionnaires and blood samples were collected from Iraqi male refugees. Genome-wide analysis more differentially methylated Cp (CpG dinucleotide specific DNA) in the LH vs HH group comparison, than in the HL vs HH group comparison. Genes associated with HPA--axis function, NR3CI and ERBP5, show significant methylation differences in the regulatory region of the genes. There was a satisfactory significant difference in DNA methylation in cg16012111 within the in FKBPS gene and a satisfactory significant difference in DNA methylation om cg00629244 within the in NR3C1 gene separately, in both group comparisons (HL vs HH and LH vs HH). It was observed that individuals with high trauma and high PTSD symptoms were more likely to have higher methylation in those loci. Furthermore, the interaction of DNA methylation of these CpG sites and trauma was the best regression predictor of PTSD symptoms. Epigenetics has great clinical implications, providing valuable information on disease risk, prognosis, and symptom severity.