Personalized Medicine in Veterans with Traumatic Brain Injuries

Abstract

The study was designed to identify clinically accessible molecular biomarkers of traumatic brain injury (TBI) prior to definitive clinical diagnosis. Specifically, these studies were meant to identify, characterize, and validate small noncoding (snc) RNA biomarker species whose content in peripheral blood mononuclear cells (PBMC) could help to identify TBI cases from the Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veteran population. In initial Biomarker Discovery studies using high-throughput array platforms, we identified 13 candidate sncRNA biomarkers that are differentially regulated in PBMC of mTBI compared to non-TBI control cases. In follow-up Biomarker Validation studies using an independent cohort of 58 veteran cases, we confirmed that 4 small nucleolar RNAs (snoRNAs), ACA48, U35, U55, and U83A, are significantly down-regulated in PBMC from veterans with mTBI and PTSD compared to non-TBI, control subjects with PTSD only. The snoRNA biomarkers are able to dissect subjects with comorbid mTBI and PTSD from PTSD subjects without mTBI with 100% sensitivity, 81% accuracy, and 72% specificity. No significant differential expression of snoRNA biomarkers was found in mTBI subjects without comorbid PTSD. With the exception of U55, we also found no significant differential expression of snoRNA biomarkers in subjects with PTSD. Additional application of the 4 snoRNA biomarker to current diagnostic criteria may provide an objective biomarker pattern to help identify veterans with comorbid mTBI and PTSD. Outcomes from our studies suggest that biological interactions between TBI and PTSD may contribute to the clinical features of mTBI with comorbid PTSD. Thus, ongoing and future investigations on mTBI mechanisms or TBI biomarkers should carefully consider their interactions with PTSD.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2014
Accession Number
ADA610691

Entities

People

  • Giulio Maria Pasinetti

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Anxiety Disorders
  • Brain Injuries
  • Cellular Structures
  • Health Services
  • Medical Personnel
  • Neurodegeneration
  • Therapy
  • Traumatic Stress Disorder

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