Identifying Dysregulated Chemokines as Biomarkers for PTSD: A Protein-Protein Interaction Analysis

Identifying Dysregulated Chemokines as Biomarkers for PTSD: A Protein-Protein Interaction Analysis Xian-Zhang Hu1,2, Lei Zhang1, Xiao Xia Li1,2, David M. Benedek1, Biomarker Study Group and Robert J. Ursano1 1 Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA 2 Henry M. Jackson Foundation for the Advancement of Military Medicine Subjects: This project was designed as before-and-after and case-control studies to examine changes in blood cytokine prior to and after development. Participants were volunteers with or without PTSD in Guamanian National Guard Soldiers (NGS) from April of 2013 to August of 2014. The NGS were deployed to Afghanistan in support of U.S. combat operations during the first year of the study period. They were voluntarily in an anonymous self-report behavioral health survey 3 months (April 2013) prior to their deployment (pre-) to Iraq, and then again 3 months after their deployment (post-, August 2014). The study began with 526 NGS. Study population were noticeably loosed throughout the study (Figure 1)1. Survey measures. PTSD symptoms were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report measure with well-established validity and reliability. Current PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 50. PTSD symptom severity was determined using the PCL total score. Demographic data, such as age, gender and race, were collected. Controls (non-PTSD) were age-, race, deployment time, and sex-matched subjects. All study procedures were approved by the Institutional Review Board at the Uniformed Service University (USUHS) and all participants were given written informed consent. Post-traumatic stress disorder (PTSD) is a severe psychological condition that affects both civilians and military personnel with prevalence rates exceeding 7% and 12%, respectively, in the United States. The incidence of
RITM0037075
Post-traumatic stress disorder (PTSD) is a severe psychological condition that affects both civilians and military personnel with prevalence rates exceeding 7% and 12%, respectively, in the United States. The incidence of PTSD has risen significantly in the veteran population as a result of the Iraq and Afghanistan Wars, with approximately 10-18% of combat troops who served in Operation Enduring Freedom or Operation Iraqi Freedom experiencing this disorder. Furthermore, PTSD can lead to immune system dysregulation, exacerbating the condition. Higher rates of immune system diseases such as rheumatism, sarcoidosis, and multiple sclerosis have been reported by Gulf War veterans. In individuals with PTSD, cytokines such as chemokines, interferons (INF), interleukins (IL), lymphokines, and tumor necrosis factors (TNF) have been found to be dysregulated. People with PTSD have increased levels of peripheral cytokines when compared to healthy controls of similar age and gender, indicating a general inflammatory state in PTSD patients. Previously, we used both before-and-after and case-control studies to search for potential chemokine biomarkers associated with PTSD in US military service members deployed to Iraq and Afghanistan1. Blood samples and scores of the PTSD Checklist (PCL) were obtained from soldiers pre- and post-deployment. Forty chemokines were measured using the Bio-Plex Pro Human Chemokine Panel Assays. Our data showed that PTSD was associated with CCL2, CCL15, CCL22, CCL25, CXCL2, and CXCL12. In addition, CCL11, CCL13, CCL20, and CCL25 were correlated with PTSD symptom severity1. Our data, for the first time, suggest that these dysregulated chemokines may serve as biomarkers for PTSD. To better understand the biological link between cytokines and PTSD, we revisited the data and conducted an analysis of the protein-protein interaction (PPI) network of cytokines. We found a unique PPIs network, in which cytokines were associated with PTSD, stress, and resilienc