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PreprintCC BY-NC-NDmedRxiv

A robust coordinated molecular response following trauma promotes recovery and protects against chronic pain and neuropsychiatric symptoms

  • B. Winfield
  • S. A. McLean
  • E. M. Branham
  • N. Stanley
  • S. L. House
  • F. L. Beaudoin
  • J. S. Stevens
  • T. C. Neylan
  • G. D. Clifford
  • L. T. Germine
  • J. P. Haran
  • A. B. Storrow
7 more authors
  • C. Lewandowski
  • P. I. Musey
  • P. L. Hendry
  • S. Sheikh
  • R. C. Kessler
  • K. J. Ressler
  • S. D. Linnstaedt1
  1. 1University of North Carolina at Chapel Hill
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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.

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Cite

BibTeXRIS
BibTeX
@misc{winfield2026robust,
  title = {{A robust coordinated molecular response following trauma promotes recovery and protects against chronic pain and neuropsychiatric symptoms}},
  author = {B. Winfield and S. A. McLean and E. M. Branham and N. Stanley and S. L. House and F. L. Beaudoin and J. S. Stevens and T. C. Neylan and G. D. Clifford and L. T. Germine and J. P. Haran and A. B. Storrow and C. Lewandowski and P. I. Musey and P. L. Hendry and S. Sheikh and R. C. Kessler and K. J. Ressler and S. D. Linnstaedt},
  howpublished = {medRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.07.26367466},
  url = {https://www.medrxiv.org/content/10.64898/2026.11.07.26367466v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - A robust coordinated molecular response following trauma promotes recovery and protects against chronic pain and neuropsychiatric symptoms
AU  - B. Winfield
AU  - S. A. McLean
AU  - E. M. Branham
AU  - N. Stanley
AU  - S. L. House
AU  - F. L. Beaudoin
AU  - J. S. Stevens
AU  - T. C. Neylan
AU  - G. D. Clifford
AU  - L. T. Germine
AU  - J. P. Haran
AU  - A. B. Storrow
AU  - C. Lewandowski
AU  - P. I. Musey
AU  - P. L. Hendry
AU  - S. Sheikh
AU  - R. C. Kessler
AU  - K. J. Ressler
AU  - S. D. Linnstaedt
PY  - 2026
DA  - 2026/11/07
PB  - medRxiv
DO  - 10.64898/2026.11.07.26367466
UR  - https://www.medrxiv.org/content/10.64898/2026.11.07.26367466v1
AB  - 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.
ER  -