Personalized Medicine in Veterans with Traumatic Brain Injuries
Final rept. 1 May 2008-30 Apr 2014
BRONX VETERANS MEDICAL RESEARCH FOUNDATION INC (VETERANS AFFAIRS) NEW YORK
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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.
- Anatomy and Physiology
- Medicine and Medical Research
- Military Forces and Organizations