Discovery and Replication of Blood-Based Proteomic Signature of PTSD in 9/11 Responders

Details

• Personal Author:
  Kotov R ; Kuan P-F ; Luft BJ ; Miao J ; Waszczuk MA ; Yang X
• Description:
  Proteomics provides an opportunity to develop biomarkers for the early detection and monitoring of post-traumatic stress disorder (PTSD). However, research to date has been limited by small sample sizes and a lack of replication. This study performed Olink Proseek Multiplex Platform profiling of 81 proteins involved in neurological processes in 936 responders to the 9/11 disaster (mean age at blood draw = 55.41 years (SD = 7.93), 94.1% white, all men). Bivariate correlations and elastic net regressions were used in a discovery subsample to identify concurrent associations between PTSD symptom severity and the profiled proteins, and to create a multiprotein composite score. In hold-out subsamples, nine bivariate associations between PTSD symptoms and differentially expressed proteins were replicated: SKR3, NCAN, BCAN, MSR1, PVR, TNFRSF21, DRAXIN, CLM6, and SCARB2 (|r| = 0.08-0.17, p < 0.05). There were three replicated bivariate associations between lifetime PTSD diagnosis and differentially expressed proteins: SKR3, SIGLEC, and CPM (OR = 1.38-1.50, p < 0.05). The multiprotein composite score retained 38 proteins, including 10/11 proteins that replicated in bivariate tests. The composite score was significantly associated with PTSD symptom severity (β = 0.27, p < 0.001) and PTSD diagnosis (OR = 1.60, 95% CI: 1.17-2.19, p = 0.003) in the hold-out subsample. Overall, these findings suggest that PTSD is characterized by altered expression of several proteins implicated in neurological processes. Replicated associations with TNFRSF21, CLM6, and PVR support the neuroinflammatory signature of PTSD. The multiprotein composite score substantially increased associations with PTSD symptom severity over individual proteins. If generalizable to other populations, the current findings may inform the development of PTSD biomarkers. [Description provided by NIOSH]
• Subjects:
  Biomarkers Emergency Responders Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Disaster Response Emergency Responders First Responders Post-traumatic Stress Disorder PTSD World Trade Center WTC
• ISSN:
  2158-3188
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; New York ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  8
• Volume:
  13
• Issue:
  1
• NIOSHTIC Number:
  nn:20066792
• Citation:
  Transl Psychiatry 2023 Jan; 13(1):8
• Contact Point Address:
  Benjamin J. Luft, Department of Medicine, Stony Brook University, Stony Brook, NY
• Email:
  Benjamin.Luft@stonybrookmedicine.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  State University of New York - Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20190701
• Source Full Name:
  Translational Psychiatry
• End Date:
  20210630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:af9aabaedf227f1b787a260e6619add4c0fcdfb512b0fef7a629ef6ac5bb5e2d3f8ab164fe6a31376a0a3d9c74647df68fb182c3cfcfcec8854a1317624f3bec
• Download URL:
  https://stacks.cdc.gov/view/cdc/231040/cdc_231040_DS1.pdf
• File Type:
  [PDF - 592.96 KB ]