Zitat:
S-025 Positive psychiatry: from mental illness to mental health 09.10.2017 | 10:00 – 11:30 | Hall Helsinki 1
An epigenetic signature of resilience?
Objective
In order to determine the epigenetic signature of the response to traumatic stress on mental ill-health, this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of symptoms of post-traumatic stress disorder (PTSD) in two prospective military cohorts (one discovery and one replication dataset).
Methods
Genome-wide DNA methylation profiles in whole blood derived DNA samples were assessed using the 450K bead chip array, before and 6 months after military deployment, while the severity of PTSD symptoms was assessed also at both time points per individual in the discovery cohort. Targeted analyses on associations between longitudinal changes in DNA methylation profiles and changes in PTSD scores were analysed in the replication cohort.
Results / Discussion
In the first cohort consisting of in male Dutch military servicemen (n= 93) the emergence of PTSD symptoms over the deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in distinct biological pathways such as "Circadian rhythm related genes”, “Wnt Signaling Pathway and Pluripotency”, “Dopaminergic neurogenesis”, “Neural Crest Differentiation”, “IL17 signaling pathway”, “TSH signaling pathway”, and “Serotonin Transporter Activity”. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male U.S. marines (n= 98; also deployed to a combat zone) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39, and HIST1H2APS2. A further analyses of resilient individuals (not showing increases in PTSD symptom scores upon exposure to combat trauma) indicated a striking opposite direction of changes in DNA methylation profiles as compared to the ' susceptible' individuals showing increases in PTSD severity.
Our study pinpoints three novel genomic regions where longitudinal changes in DNA methylation across the period of exposure to combat trauma marks differential susceptibility for PTSD.