title: Plasma Lipidomic Profiling in a Military Population of Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder with Apolipoprotein E ɛ4-Dependent Effect.
abstract: In the military population, there is high comorbidity between mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) due to the inherent risk of psychological trauma associated with combat. These disorders present with long-term neurological dysfunction and remain difficult to diagnose due to their comorbidity and overlapping clinical presentation. Therefore, we performed cross-sectional analysis of blood samples from demographically matched soldiers (total, n = 120) with mTBI, PTSD, and mTBI+PTSD and those who were considered cognitively and psychologically normal. Soldiers were genotyped for apolipoprotein E (APOE) ɛ4, and phospholipids (PL) were examined using liquid chromatography/mass spectrometry analysis. We observed significantly lower levels of several major PL classes in TBI, PTSD, and TBI+PTSD, compared with controls. PTSD severity analysis revealed that significant PL decreases were primarily restricted to the moderate-to-severe PTSD group. An examination of the degree of unsaturation showed that monounsaturated fatty acid-containing phosphatidylcholine (PC) and phosphatidylinositol (PI) species were lower in the TBI and TBI+PTSD groups. However, these PLs were unaltered among PTSD subjects, compared with controls. Similarly, ether PC (ePC) levels were lower in PTSD and TBI+PTSD subjects, relative to controls. Ratios of arachidonic acid (AA) to docosahexaenoic acid (DHA)-containing species were significantly decreased within PC and phosphatidylethanolamine (PE) classes. APOE ɛ4 (+) subjects exhibited higher PL levels than their APOE ɛ4 (-) counterparts within the same diagnostic groups. These findings suggest that PL profiles, together with APOE genotyping, could potentially aid to differentiate diagnosis of mTBI and PTSD and warrant further validation. In conclusion, PL profiling may facilitate clinical diagnosis of mTBI and PTSD currently hindered by comorbid pathology and overlapping symptomology of these two conditions.
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Tanja
authors.initials: T
authors.lastname: Emmerich
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .
authors.forename: Gogce
authors.initials: G
authors.lastname: Crynen
authors.affiliation: 4 National Intrepid Center of Excellence, Walter Reed National Military Medical Center , Bethesda, Maryland.|5 United States Army Aeromedical Research Laboratory , Rucker, Alabama.
authors.forename: Michael
authors.initials: M
authors.lastname: Dretsch
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: James
authors.initials: J
authors.lastname: Evans
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Ghania
authors.initials: G
authors.lastname: Ait-Ghezala
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Jon
authors.initials: J
authors.lastname: Reed
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: Hannah
authors.initials: H
authors.lastname: Montague
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: Helena
authors.initials: H
authors.lastname: Chaytow
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Venkatarajan
authors.initials: V
authors.lastname: Mathura
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: Justin
authors.initials: J
authors.lastname: Martin
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Pelot
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Scott
authors.initials: S
authors.lastname: Ferguson
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: Alex
authors.initials: A
authors.lastname: Bishop
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Phillips
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
authors.affiliation: 1 The Roskamp Institute , Sarasota, Florida.|2 The Open University , Buckinghamshire, United Kingdom .|3 James A. Haley Veteran's Hospital , Tampa, Florida.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
mesh_terms: D000328:Adult; D053327:Apolipoprotein E4 / Q000235:genetics*; D001924:Brain Concussion / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D008889:Military Personnel; D010743:Phospholipids / Q000097:blood*; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D010743:Phospholipids
keywords: apolipoprotein E; human studies; lipidomics; phospholipids; post-traumatic stress disorder; traumatic brain injury