Molecular signatures of post-traumatic stress disorder in war-zone-exposed veteran and active-duty soldiers

Seid Muhie; Aarti Gautam; Ruoting Yang; Burook Misganaw; Bernie J Daigle Jr; Synthia H Mellon; Janine D Flory; Duna Abu-Amara; Inyoul Lee; Kai Wang; Ryan Rampersaud; PTSD Systems Biology Consortium; Leroy Hood; Rachel Yehuda; Charles R Marmar; Owen M Wolkowitz; Kerry J Ressler; Francis J Doyle 3rd; Rasha Hammamieh; Marti Jett

doi:10.1016/j.xcrm.2023.101045

Molecular signatures of post-traumatic stress disorder in war-zone-exposed veteran and active-duty soldiers

Cell Rep Med. 2023 May 16;4(5):101045. doi: 10.1016/j.xcrm.2023.101045.

Authors

Seid Muhie¹, Aarti Gautam², Ruoting Yang², Burook Misganaw³, Bernie J Daigle Jr⁴, Synthia H Mellon⁵, Janine D Flory⁶, Duna Abu-Amara⁷, Inyoul Lee⁸, Kai Wang⁸, Ryan Rampersaud⁹; PTSD Systems Biology Consortium; Leroy Hood⁸, Rachel Yehuda⁶, Charles R Marmar⁷, Owen M Wolkowitz⁹, Kerry J Ressler¹⁰, Francis J Doyle 3rd¹¹, Rasha Hammamieh², Marti Jett¹²

Affiliations

¹ 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.
² Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
³ Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Vysnova Inc., Landover, MD 20785, USA.
⁴ Departments of Biological Sciences and Computer Science, The University of Memphis, Memphis, TN 38152, USA.
⁵ Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ Office of Mental Health, 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.
⁷ Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA.
⁸ Institute for Systems Biology, Seattle, WA 98109, USA.
⁹ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁰ McLean Hospital, Belmont, MA 02478, USA; Harvard Medical School, Boston, MA 02115, USA.
¹¹ Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02134, USA.
¹² US Army Medical Research and Development Command, HQ, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: marti.jett-tilton.civ@health.mil.

Abstract

Post-traumatic stress disorder (PTSD) is a multisystem syndrome. Integration of systems-level multi-modal datasets can provide a molecular understanding of PTSD. Proteomic, metabolomic, and epigenomic assays are conducted on blood samples of two cohorts of well-characterized PTSD cases and controls: 340 veterans and 180 active-duty soldiers. All participants had been deployed to Iraq and/or Afghanistan and exposed to military-service-related criterion A trauma. Molecular signatures are identified from a discovery cohort of 218 veterans (109/109 PTSD+/-). Identified molecular signatures are tested in 122 separate veterans (62/60 PTSD+/-) and in 180 active-duty soldiers (PTSD+/-). Molecular profiles are computationally integrated with upstream regulators (genetic/methylation/microRNAs) and functional units (mRNAs/proteins/metabolites). Reproducible molecular features of PTSD are identified, including activated inflammation, oxidative stress, metabolic dysregulation, and impaired angiogenesis. These processes may play a role in psychiatric and physical comorbidities, including impaired repair/wound healing mechanisms and cardiovascular, metabolic, and psychiatric diseases.

Keywords: active duty; angiogenesis; inflammatory response; metabolic dysregulation; molecular signature; multi-omics; oxidative stress; post-traumatic stress disorder; veterans; wound healing.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Humans
Inflammation
Military Personnel* / psychology
Proteomics
Stress Disorders, Post-Traumatic* / diagnosis
Stress Disorders, Post-Traumatic* / genetics
Stress Disorders, Post-Traumatic* / psychology
Veterans* / psychology