. 2022 Dec;47(13):2300-2308.

doi: 10.1038/s41386-022-01359-5. Epub 2022 Jun 18.

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Jacqueline R Kulbe¹, Sonia Jain², Lindsay D Nelson³, Frederick K Korley⁴, Pratik Mukherjee^{5

6}, Xiaoying Sun², David O Okonkwo⁷, Joseph T Giacino^{8

9}, Mary J Vassar^{10

11}, Claudia S Robertson¹², Michael A McCrea³, Kevin K W Wang¹³, Nancy Temkin¹⁴, Christine L Mac Donald¹⁴, Sabrina R Taylor^{10

11}, Adam R Ferguson¹⁰, Amy J Markowitz¹⁰, Ramon Diaz-Arrastia¹⁵, Geoffrey T Manley^{10

11}, Murray B Stein^{16

17

18}; TRACK-TBI Investigators

Collaborators, Affiliations

Collaborators

TRACK-TBI Investigators:
Neeraj Badjatia, Ann-Christine Duhaime, V Ramana Feeser, C Dirk Keene, Christopher Madden, Randall Merchant, Ava Puccio, David Schnyer, Sabrina R Taylor, Alex Valadka, John K Yue, Esther L Yuh, Ross Zafonte

Affiliations

¹ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
² Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.
³ Departments of Neurosurgery and Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Radiology & Biomedical Imaging, UCSF, San Francisco, CA, USA.
⁶ Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA, USA.
⁷ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁸ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
⁹ Spaulding Rehabilitation Hospital, Charlestown, MA, USA.
¹⁰ Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA.
¹¹ Department of Neurological Surgery, UCSF, San Francisco, CA, USA.
¹² Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
¹³ Department of Emergency Medicine, University of Florida, Gainesville, FL, USA.
¹⁴ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
¹⁵ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. mstein@health.ucsd.edu.
¹⁷ School of Public Health, University of California, San Diego, La Jolla, CA, USA. mstein@health.ucsd.edu.
¹⁸ VA San Diego Healthcare System, San Diego, CA, USA. mstein@health.ucsd.edu.

PMID: 35717463
PMCID: PMC9630517
DOI: 10.1038/s41386-022-01359-5

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Jacqueline R Kulbe et al. Neuropsychopharmacology. 2022 Dec.

. 2022 Dec;47(13):2300-2308.

doi: 10.1038/s41386-022-01359-5. Epub 2022 Jun 18.

Authors

Collaborators

TRACK-TBI Investigators:
Neeraj Badjatia, Ann-Christine Duhaime, V Ramana Feeser, C Dirk Keene, Christopher Madden, Randall Merchant, Ava Puccio, David Schnyer, Sabrina R Taylor, Alex Valadka, John K Yue, Esther L Yuh, Ross Zafonte

Affiliations

¹ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
² Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.
³ Departments of Neurosurgery and Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Radiology & Biomedical Imaging, UCSF, San Francisco, CA, USA.
⁶ Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA, USA.
⁷ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁸ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
⁹ Spaulding Rehabilitation Hospital, Charlestown, MA, USA.
¹⁰ Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA.
¹¹ Department of Neurological Surgery, UCSF, San Francisco, CA, USA.
¹² Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
¹³ Department of Emergency Medicine, University of Florida, Gainesville, FL, USA.
¹⁴ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
¹⁵ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. mstein@health.ucsd.edu.
¹⁷ School of Public Health, University of California, San Diego, La Jolla, CA, USA. mstein@health.ucsd.edu.
¹⁸ VA San Diego Healthcare System, San Diego, CA, USA. mstein@health.ucsd.edu.

PMID: 35717463
PMCID: PMC9630517
DOI: 10.1038/s41386-022-01359-5

Erratum in

Correction to: Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury.
Kulbe JR, Jain S, Nelson LD, Korley FK, Mukherjee P, Sun X, Okonkwo DO, Giacino JT, Vassar MJ, Robertson CS, McCrea MA, Wang KKW, Temkin N, Mac Donald CL, Taylor SR, Ferguson AR, Markowitz AJ, Diaz-Arrastia R, Manley GT, Stein MB; TRACK-TBI Investigators. Kulbe JR, et al. Neuropsychopharmacology. 2022 Dec;47(13):2332. doi: 10.1038/s41386-022-01466-3. Neuropsychopharmacology. 2022. PMID: 36180785 Free PMC article. No abstract available.

Abstract

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77-0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98-1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. Relationship of Blood Biomarker Concentrations to Duration of Posttraumatic Amnesia.**
a (top): Day-of-injury plasma GFAP concentrations and duration of posttraumatic amnesia (PTA). b (bottom): Day-of-injury serum hsCRP concentrations and duration of posttraumatic amnesia (PTA).

**Fig. 2. Day-of-injury blood biomarker concentrations among those without and with probable PTSD at 6-month outcome.**
a (top): Day-of-injury plasma GFAP concentrations among those without (“no”) and with (“yes”) probable PTSD at 6-month outcome. b (bottom): Day-of-injury serum hsCRP concentrations among those without (“no”) and with (“yes”) probable PTSD at 6-month outcome post-injury.

See this image and copyright information in PMC

References

1. Nelson LD, Temkin NR, Dikmen S, Barber J, Giacino JT, Yuh E, et al. Recovery after mild traumatic brain injury in patients presenting to US Level I trauma centers: A transforming research and clinical knowledge in Traumatic Brain Injury (TRACK-TBI) Study. JAMA Neurol. 2019;76:1049–59. - PMC - PubMed
1. Agtarap SD, Campbell-Sills L, Jain S, Sun X, Dikmen S, Levin H, et al. Satisfaction with life after mild traumatic brain injury: A TRACK-TBI study. J Neurotrauma. 2021;38:546–54. - PMC - PubMed
1. Howlett JR, Nelson LD, Stein MB. Mental health consequences of traumatic brain injury. Biol Psychiatry. 2022;91:413–20. - PMC - PubMed
1. Albrecht JS, Abariga SA, Rao V, Wickwire EM. Incidence of new neuropsychiatric disorder diagnoses following traumatic brain injury. J Head Trauma Rehabil. 2020;35:E352–E360. - PubMed
1. Stein MB, Jain S, Giacino JT, Levin H, Dikmen S, Nelson LD, et al. Risk of posttraumatic stress disorder and major depression in civilian patients after mild traumatic brain injury: A TRACK-TBI study. JAMA Psychiatry. 2019;76:249–58. - PMC - PubMed

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Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Collaborators

Affiliations

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Authors

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous