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Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

Publication ,  Journal Article
Werner, JK; Albrecht, J; Capaldi, VF; Jain, S; Sun, X; Mukherjee, P; Williams, SG; Collen, J; Diaz-Arrastia, R; Manley, GT; Krystal, AD ...
Published in: Neurology
April 23, 2024

BACKGROUND AND OBJECTIVES: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics. RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers. DISCUSSION: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.

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Published In

Neurology

DOI

EISSN

1526-632X

Publication Date

April 23, 2024

Volume

102

Issue

8

Start / End Page

e209269

Location

United States

Related Subject Headings

  • Ubiquitin Thiolesterase
  • Sleep Initiation and Maintenance Disorders
  • Prospective Studies
  • Neurology & Neurosurgery
  • Inflammation
  • Humans
  • Glial Fibrillary Acidic Protein
  • C-Reactive Protein
  • Brain Injuries, Traumatic
  • Biomarkers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Werner, J. K., Albrecht, J., Capaldi, V. F., Jain, S., Sun, X., Mukherjee, P., … TRACK-TBI Investigators, . (2024). Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study. Neurology, 102(8), e209269. https://doi.org/10.1212/WNL.0000000000209269
Werner, J Kent, Jennifer Albrecht, Vincent F. Capaldi, Sonia Jain, Xiaoying Sun, Pratik Mukherjee, Scott G. Williams, et al. “Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.Neurology 102, no. 8 (April 23, 2024): e209269. https://doi.org/10.1212/WNL.0000000000209269.
Werner JK, Albrecht J, Capaldi VF, Jain S, Sun X, Mukherjee P, et al. Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study. Neurology. 2024 Apr 23;102(8):e209269.
Werner, J. Kent, et al. “Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.Neurology, vol. 102, no. 8, Apr. 2024, p. e209269. Pubmed, doi:10.1212/WNL.0000000000209269.
Werner JK, Albrecht J, Capaldi VF, Jain S, Sun X, Mukherjee P, Williams SG, Collen J, Diaz-Arrastia R, Manley GT, Krystal AD, Wickwire E, TRACK-TBI Investigators. Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study. Neurology. 2024 Apr 23;102(8):e209269.

Published In

Neurology

DOI

EISSN

1526-632X

Publication Date

April 23, 2024

Volume

102

Issue

8

Start / End Page

e209269

Location

United States

Related Subject Headings

  • Ubiquitin Thiolesterase
  • Sleep Initiation and Maintenance Disorders
  • Prospective Studies
  • Neurology & Neurosurgery
  • Inflammation
  • Humans
  • Glial Fibrillary Acidic Protein
  • C-Reactive Protein
  • Brain Injuries, Traumatic
  • Biomarkers