Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study

Mota, Natalie; Han, Shizhong; Harpaz‐Rotem, Ilan; Maruff, Paul; Krystal, John H.; Southwick, Steven M.; Gelernter, Joel; Pietrzak, Robert H.

doi:10.1002/da.22698

Cited by 20 publications

(15 citation statements)

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“…In particular, the presence of the ε4 allele is associated with impaired lipid transport in the periphery and the brain (Marais, 2019). Additionally, ε4 carriers have poorer outcomes after insults to the brain (Mota et al, 2017). In examining the influence of ε4 carrier status on the association between lipids and the diagnosis of TBI and PTSD, the greatest number of peripheral lipid changes were seen in the ε4− mTBI + PTSD group, while this was not the case in the ε4 + mTBI + PTSD group, indicating a differential response to injury in the presence of ε4 allele.…”

Section: Discussionmentioning

confidence: 99%

“…Apolipoprotein E (ApoE, encoded by the APOE gene) is a constituent of lipoprotein particles responsible for transporting lipids from the bloodstream to various tissues including the brain (Jonas and Phillips, 2008;Tudorache et al, 2017). Among the three major APOE polymorphisms, the ε4 allele is known to have impaired lipid transport to the brain and is also associated with worse cognitive outcomes in both TBI and PTSD (Mota et al, 2017). ApoE/lipoprotein complexes facilitate lipid transport to the BBB where lipids are processed and subsequently transported into the brain by fatty acid binding proteins (FABP) as well as by other transporters (Mitchell and Hatch, 2011;Sepe et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…This systematic review aims to critically appraise the research on risk and protective factors of MCI/dementia among adults with PTSD. Potential and anticipated risk factors may include well-known comorbidities of PTSD, such as major depressive disorder, 23 substance use disorder, 24 obesity 25 and other associated genetic or biological factors (ie, APOE genotype 26 or female sex, 27 respectively). Potential and anticipated protective factors may include cognitive training or physical exercise.…”

Section: Objectivesmentioning

confidence: 99%

Risk and protective factors of dementia among adults with post-traumatic stress disorder: a systematic review protocol

et al. 2020

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IntroductionPost-traumatic stress disorder (PTSD) is associated with an increased risk of dementia. Individual epidemiological studies have controlled for several confounders of the relationship between PTSD and increased dementia risk, yet particular risk factors underlying this relationship have not been determined. This systematic review protocol aims to identify risk and protective factors of dementia among adults with PTSD.Methods and analysisWe will conduct an electronic search of the databases: PubMed, CINAHL, PsychINFO, The Cochrane Library, Scopus and ProQuest Dissertation and Theses Global. After screening the studies, quantitative synthesis will be performed, if possible. Otherwise, a narrative synthesis will be performed. We will include randomised controlled trials and other types of research evidence including longitudinal cohort studies. Strength of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations method. Examples of variables that will be extracted are: year of PTSD diagnosis, comorbid conditions, health behaviours, pharmacological treatments and year of mild cognitive impairment or dementia diagnosis. We developed this systematic review protocol according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement.Ethics and disseminationThe proposed study will not collect individual-level data and, therefore, does not require ethical approval. Results of this study will provide current evidence on risk and protective factors of dementia in adults with PTSD. Findings will be disseminated in peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42019128553.

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“…To date, there have been a limited number of genetic studies of psychological resilience, with most of these investigating candidate genes (e.g., SLC6A4 *5HTTLPR) (Stein, Campbell‐Sills, & Gelernter, ) for what is certainly a highly polygenic trait and, often focusing exclusively on PTSD as the outcome (e.g., APOE epsilon4, or, nitric oxide pathway genes) (Bruenig et al, ; Mota et al, ). One recent study examined self‐reported resilience along with polygenic risk for depression in relation to major depression, finding additive effects, consistent with the notion that psychological characteristics associated with self‐assessed resilience can be considered a buffer against stress (Navrady et al, ).…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide analyses of psychological resilience in U.S. Army soldiers

Stein

Choi

Jain

et al. 2019

American J of Med Genetics Pt B

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Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome-wide association studies (GWASs) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self-assessed resilience (N = 11,492) was found to have significant common-variant heritability (h 2 = 0.162, se = 0.050, p = 5.37 × 10 −4 ), and to be significantly negatively genetically correlated with neuroticism (r g = −0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome-wide significant locus on an intergenic region on Chr 4 upstream from doublecortin-like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [p = 5.65 × 10 −9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch-like family member 36 (KLHL36) was detected at gene-wise genomewide significance [p = 1.89 × 10 −6 ]. A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very

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Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study

Cited by 20 publications

References 80 publications

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

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

Risk and protective factors of dementia among adults with post-traumatic stress disorder: a systematic review protocol

Genome‐wide analyses of psychological resilience in U.S. Army soldiers

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