Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

Claire J C Huguenard; Adam Cseresznye; James E Evans; Sarah Oberlin; Heather Langlois; Scott Ferguson; Teresa Darcey; Aurore Nkiliza; Michael Dretsch; Michael Mullan; Fiona Crawford; Laila Abdullah

doi:10.3389/fphys.2020.00012

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

Front Physiol. 2020 Jan 31:11:12. doi: 10.3389/fphys.2020.00012. eCollection 2020.

Authors

Claire J C Huguenard^{1

2

3}, Adam Cseresznye^{1

3}, James E Evans^{1

3}, Sarah Oberlin^{1

3}, Heather Langlois^{1

3}, Scott Ferguson^{1

2

3}, Teresa Darcey^{1

3}, Aurore Nkiliza^{1

3}, Michael Dretsch^{4

5}, Michael Mullan^{1

2

3}, Fiona Crawford^{1

2

3}, Laila Abdullah^{1

2

3}

Affiliations

¹ The Roskamp Institute, Sarasota, FL, United States.
² School of Life, Health and Chemical Sciences, The Open University, Milton Keynes, United Kingdom.
³ James A. Haley Veterans' Hospital, Tampa, FL, United States.
⁴ US Army Medical Research Directorate-West, Walter Reed Army Institute of Research, Joint Base Lewis-McChord, Tacoma, WA, United States.
⁵ U.S. Army Aeromedical Research Laboratory, Fort Rucker, AL, United States.

Abstract

The differential diagnosis between mild Traumatic Brain Injury (mTBI) sequelae and Post-Traumatic Stress Disorder (PTSD) is challenging due to their symptomatic overlap and co-morbidity. As such, there is a need to develop biomarkers which can help with differential diagnosis of these two conditions. Studies from our group and others suggest that blood and brain lipids are chronically altered in both mTBI and PTSD. Therefore, examining blood lipids presents a minimally invasive and cost-effective approach to identify promising biomarkers of these conditions. Using liquid chromatography-mass spectrometry (LC-MS) we examined hundreds of lipid species in the blood of healthy active duty soldiers (n = 52) and soldiers with mTBI (n = 21), PTSD (n = 34) as well as co-morbid mTBI and PTSD (n = 13) to test whether lipid levels were differentially altered with each. We also examined if the apolipoprotein E (APOE) ε4 allele can affect the association between diagnosis and peripheral lipid levels in this cohort. We show that several lipid classes are altered with diagnosis and that there is an interaction between diagnosis and the ε4 carrier status on these lipids. Indeed, total lipid levels as well as both the degree of unsaturation and chain lengths are differentially altered with diagnosis and ε4 status, specifically long chain unsaturated triglycerides (TG) and both saturated and mono-unsaturated diglycerides (DG). Additionally, an examination of lipid species reveals distinct profiles in each diagnostic group stratified by ε4 status, mainly in TG, saturated DG species and polyunsaturated phosphatidylserines. In summary, we show that peripheral lipids are promising biomarker candidates to assist with the differential diagnosis of mTBI and PTSD. Further, ε4 carrier status alone and in interaction with diagnosis has a strong influence on peripheral lipid levels. Therefore, examining ε4 status along with peripheral lipid levels could help with differential diagnosis of mTBI and PTSD.

Keywords: apolipoprotein ε4; biomarkers; lipids; mass spectrometry; post-traumatic stress disorder; traumatic brain injury.