title: Apolipoprotein E: the resilience gene.
abstract: The apolipoprotein E (apoE) gene has been implicated in various conditions, most notably Alzheimer's disease and coronary artery disease. A predisposing role of the apoE4 isoform and a protective role of apoE2 isoform in those diseases have been documented. Here we investigated the role of apoE in resilience to trauma. Three hundred and forty-three US veterans were genotyped for apoE and were assessed for their lifetime trauma exposure (trauma score, T) and severity of posttraumatic stress disorder symptoms (PCL). The ratio PCL/T indicates sensitivity to trauma; hence, its inverse indicates resilience, R, to trauma. We found a significantly higher resilience in participants with apoE genotype containing the E2 allele (E2/2, E2/3) as compared to participants with the E4 allele (E4/4, E4/3). In addition, when the categorical apoE genotype was reexpressed as the number of cysteine residues per apoE mole (CysR/mole), a highly significant positive association was found between resilience and CysR/mole, such that resilience was systematically higher as the number of CysR/mole increased, from zero CysR/mole in E4/4 to four CysR/mole in E2/2. These findings demonstrate the protective role of the CysR/mole apoE in resilience to trauma: the more CysR/mole, the higher the resilience. Thus, they are in accord with other findings pointing to a generally protective role of increasing number of CysR/mole (from E4/4 to E2/2) in other diseases. However, unlike other conditions (e.g., Alzheimer's disease and coronary artery disease), resilience to trauma is not a disease but an adaptive response to trauma. Therefore, the effects of apoE seem to be more pervasive along the CysR/mole continuum, most probably reflecting underlying effects on brain synchronicity and its variability that we have documented previously (Leuthold et al., Exp Brain Res 226:525-536, 2013).
authors.affiliation: Department of Veterans Affairs Health Care System, Brain Sciences Center (11B), Minneapolis VAHCS, One Veterans Drive, Minneapolis, MN, 55417, USA. lmjames@umn.edu.|Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA. lmjames@umn.edu.|Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, 55455, USA. lmjames@umn.edu.|Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, USA. lmjames@umn.edu.
authors.forename: Lisa M
authors.identifier: 0000-0001-9021-0690
authors.initials: LM
authors.lastname: James
authors.affiliation: Department of Veterans Affairs Health Care System, Brain Sciences Center (11B), Minneapolis VAHCS, One Veterans Drive, Minneapolis, MN, 55417, USA.|Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.|Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, USA.|Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Engdahl
authors.affiliation: Department of Veterans Affairs Health Care System, Brain Sciences Center (11B), Minneapolis VAHCS, One Veterans Drive, Minneapolis, MN, 55417, USA.|Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.|Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.|Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, USA.|Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
authors.forename: Apostolos P
authors.initials: AP
authors.lastname: Georgopoulos
mesh_terms: D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000067073:Psychological Trauma / Q000150:complications / Q000235:genetics*; D055500:Resilience, Psychological; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D014481:United States; D014728:Veterans / Q000706:statistics & numerical data
chemical_list: D001057:Apolipoproteins E
keywords: ApoE; Resilience; Trauma