A robust coordinated molecular response following trauma promotes recovery and protects against chronic pain and neuropsychiatric symptoms
Year: 2026
Type: preprint
Abstract: The biological mechanisms governing recovery versus chronicity of adverse posttraumatic neuropsychiatric sequelae (APNS) remain poorly understood. Here, we characterized longitudinal molecular changes among trauma survivors across ten APNS domains, including pain, anxiety, and depression. Recovery across these diverse clinical outcomes was associated with a shared, temporally coordinated transcriptional signature, characterized by early innate immune activation, subsequent homeostatic and wound-healing processes, and later adaptive immune responses. In contrast, chronic APNS trajectories exhibited limited transcriptional remodeling. We derived and externally validated an RNA-based Recovery Score (RRS) capturing the shared molecular response underlying recovery. Higher RRS was associated with greater clinical recovery, elevated peritraumatic cortisol, and lower cumulative stress exposure. Drug-response profiling identified candidate compounds predicted to mimic recovery-associated transcriptional changes. Together, these findings support posttraumatic recovery as an active biological process and identify shared molecular pathways that may be harnessed to prevent multiple adverse posttraumatic outcomes.
Source: medRxiv
Authors: Brittanie Winfield, Samuel A McLean, Erica M Branham, Natalie Stanley, Stacey L House, Francesca L Beaudoin, Jennifer S Stevens, Thomas C Neylan, Gari D Clifford, Laura T Germine, John P Haran, Alan B Storrow, Christopher Lewandowski, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Ronald C Kessler, Kerry J Ressler, Sarah D Linnstaedt
Institutions: University of North Carolina at Chapel Hill, Washington University in St. Louis, Brown University, Emory University, University of California, San Francisco, Johns Hopkins University, Albert Einstein College of Medicine, University of Massachusetts Chan Medical School, Vanderbilt University Medical Center, Henry Ford Health, Indiana University School of Medicine, University of Florida, University of Florida Health Science Center, Harvard University
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W7225661066
Cites:
Cited by:
Related to: