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

• Published in: Brain, behavior, and immunity Vol. 113; pp. 303 - 316
• Main Authors: Muhie, Seid, Gautam, Aarti, Misganaw, Burook, Yang, Ruoting, Mellon, Synthia H., Hoke, Allison, Flory, Janine, Daigle, Bernie, Swift, Kevin, Hood, Leroy, Doyle, Francis J., Wolkowitz, Owen M., Marmar, Charles R., Ressler, Kerry, Yehuda, Rachel, Hammamieh, Rasha, Jett, Marti
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2023
• Subjects: Active duty soldiers; Chronic PTSD; Comorbidities; Homeostasis; Multi-omics; post-traumatic stress disorder (PTSD); Recent onset PTSD; Veterans; Chronic PTSD; Active duty soldiers; Veterans; CAPS-4; BDI; DMP; FCC; PCL-5; Homeostasis; GO; Multi-omics; DEP; PTSD; Comorbidities; SBC; FDR; PHQ; KEGG; TBI; post-traumatic stress disorder (PTSD); Recent onset PTSD; DSM; BMI; ELISA
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.07.015

•Systems-level multi-omics profiling revealed molecular signatures of PTSD progression.•Multi-omics alterations in recent PTSD were broadly related to homeostatic processes.•Indicative of recalibration to mitigate pathological trajectory at the earlier phase.•Whereas molecular changes in chronic PTSD were implicated in multi-system syndromes.•Pointing the less likely ability of the body’s self-remission from chronic PTSD. 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.