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Immunity genes associated with post-traumatic stress development
Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder which is particularly challenging to study given the presence or trigger of a traumatic event, for example serving in a combat zone. Researchers have succeeded in a new study in identifying discrete groups of co-regulated genes associated with PTSD development in blood samples from U.S. Marines before and after deployment in combat zones. The relevant genes are associated with immune responsiveness.

The study comes from researchers at the Veterans Affairs San Diego Healthcare System and University of California, San Diego School of Medicine, with colleagues in New York and the United Kingdom. Co-senior author Dr Christopher H. Woelk, reader in genomics and bioinformatics at University of Southampton and assistant adjunct professor at UC San Diego School of Medicine, explained: "The odds of obtaining a sample both before and after a traumatic event are incredibly small. Under this experimental design, not only can we identify differences between U.S. Marines with PTSD and without, but we can go back in time, so to speak, to see if any of the Marines who eventually developed PTSD contain prognostic signatures that might be indicative of eventual PTSD emergence. In this vein, we are able to start labeling findings as being putatively 'causal' in nature." The study is published in an advanced online version in the March 10 issue of the journal Molecular Psychiatry.

In the study, the research team used a system called whole-transcriptome RNA-Seq gene expression to examine gene expression from blood leukocyte samples taken from 188 U.S. Marines both pre- and post-deployment to conflict zones. The researchers identified discrete co-expression modules (groups of co-regulated genes). One module was identified at both pre- and post-deployment as containing proposed causal PTSD development signatures. This module was enriched in innate-immune response and interferon-signalling genes. Interferons are normally released by host cells in response to infections. The results were replicated in a second independent sample of 96 U.S. Marines. A second module was identified post-deployment containing PTSD resiliency signatures. This module was rich in genes associated with haemostasis and wound healing.

Co-author Dr Dewleen G. Baker of the VA Center of Excellence for Stress and Mental Health and Department of Psychiatry at UC San Diego commented:  "What's interesting is that molecular signatures of innate immunity and interferon signaling were identified both after developing PTSD as well as before developing PTSD. The question to ask is what's stimulating an interferon response prior to PTSD development. The answer could be any number of factors, ranging from a simple explanation of increased anticipatory stress prior to deployment or more complex scenarios where individuals may have a higher viral load. It's a question for future studies."
The researchers conclude that their findings suggest two lines of further enquiry. The first would be development of a blood panel of predictive biomarkers for identification of individuals at greater risk of PTSD development. The second would be utilising the molecular information from blood samples for design of targeted therapies for either treatment or prevention of PTSD.

Breen MS, Maihofer AX, Glatt SJ, Tylee DS, Chandler SD, Tsuang MT, Risbrough VB, Baker DG, O'Connor DT, Nievergelt CM, Woelk CH. Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry advance online publication 10 March 2015; doi: 10.1038/mp.2015.9

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