Integrated analysis of proteomics, epigenomics and metabolomics data revealed divergent pathway activation patterns in the recent versus chronic post-traumatic stress disorder

Authors

Seid Muhie, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; The Geneva Foundation, Silver Spring, MD 20910, USA. Electronic address: smuhie@genevausa.org.
Aarti Gautam, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Burook Misganaw, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Vysnova Inc. Landover, MD 20785, USA.
Ruoting Yang, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Synthia H. Mellon, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
Allison Hoke, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Janine Flory, Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY 10468, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10468, USA.
Bernie Daigle, Departments of Biological Sciences and Computer Science, The University of Memphis, Memphis, TN 38152, USA.
Kevin Swift, Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

Abstract

Metabolomics, proteomics and DNA methylome assays, when done in tandem from the same blood sample and analyzed together, offer an opportunity to evaluate the molecular basis of post-traumatic stress disorder (PTSD) course and pathogenesis. We performed separate metabolomics, proteomics, and DNA methylome assays on blood samples from two well-characterized cohorts of 159 active duty male participants with relatively recent onset PTSD (<1.5 years) and 300 male veterans with chronic PTSD (>7 years). Analyses of the multi-omics datasets from these two independent cohorts were used to identify convergent and distinct molecular profiles that might constitute potential signatures of severity and progression of PTSD and its comorbid conditions. Molecular signatures indicative of homeostatic processes such as signaling and metabolic pathways involved in cellular remodeling, neurogenesis, molecular safeguards against oxidative stress, metabolism of polyunsaturated fatty acids, regulation of normal immune response, post-transcriptional regulation, cellular maintenance and markers of longevity were significantly activated in the active duty participants with recent PTSD. In contrast, we observed significantly altered multimodal molecular signatures associated with chronic inflammation, neurodegeneration, cardiovascular and metabolic disorders, and cellular attritions in the veterans with chronic PTSD. Activation status of signaling and metabolic pathways at the early and late timepoints of PTSD demonstrated the differential molecular changes related to homeostatic processes at its recent and multi-system syndromes at its chronic phase. Molecular alterations in the recent PTSD seem to indicate some sort of recalibration or compensatory response, possibly directed in mitigating the pathological trajectory of the disorder.

Publication Title

Brain, behavior, and immunity

Recommended Citation

Muhie, S., Gautam, A., Misganaw, B., Yang, R., Mellon, S. H., Hoke, A., Flory, J., Daigle, B., & Swift, K. (2023). Integrated analysis of proteomics, epigenomics and metabolomics data revealed divergent pathway activation patterns in the recent versus chronic post-traumatic stress disorder. Brain, behavior, and immunity, 113, 303-316. https://doi.org/10.1016/j.bbi.2023.07.015