Evidence for distinct biological perturbations in PTSD with severe child abuse: implications for PTSD biomarkers

Abstract

Rationale/statement of the problem : Evidence for distinct biological perturbations in posttraumatic stress disorder (PTSD) with severe child abuse versus no child abuse: consequences for robust biomarkers for PTSD. The identification of biomarkers for PTSD has been difficult, likely due to inter-individual differences in genetic risk factors and environmental exposures. The aim of the current study was to interrogate the influences of the environment on gene expression profiles by characterizing biological differences in PTSD after severe child abuse versus PTSD after adult trauma. Methods : A total of 396 trauma-exposed individuals were included in this study. The PTSD symptomatic scale (PSS), clinician-administered PTSD scales (CAPS), childhood trauma questionnaire, and trauma events inventory were used to assess current clinical PTSD and childhood and adult trauma severity. Whole blood gene expression and DNA methylation was measured on Illumina Human-HT12v3 and Human Methylation 450k arrays. Analysis was performed by using R software. Results : Of 741 transcripts significantly associated with current PTSD severity, only 2% was associated with PTSD in both, individuals exposed to child abuse and adult trauma (N=32) and individuals exposed to adult trauma only (N=29), after accounting for adult trauma severity. Expression differences were also reflected in DNA methylation differences between the groups. Functional annotations revealed distinct biological pathways enriched among the expression profiles associated with PTSD in these two groups. Conclusion : These data suggest that PTSD occurring after severe child abuse is biologically distinct from PTSD after adult trauma, therefore, accounting for different environmental variables is crucial for identification of biomarkers for PTSD.

Keywords

• PTSD
• child abuse
• trauma
• gene expression
• methylation