@article{8b4725b143b347ea8d8e9b6b7a69a43b,
title = "Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study",
abstract = "Background: Although the ε4 allele of the apolipoprotein E (APOE) gene and posttraumatic stress disorder (PTSD) have been linked to cognitive dysfunction and dementia risk, it is unknown whether they interact to predict cognitive dysfunction. Methods: We analyzed data from European-American (EA) veterans who participated in the National Health and Resilience in Veterans Study (NHRVS): main sample (n = 1,386) and primary replication sample (n = 509). EAs from the Yale–Penn Study cohort (n = 948) served as a second replication sample. Multivariable analyses were conducted to evaluate the predictive effects of ε4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of ε4 carrier status. Results: APOE ε4 allele carrier status (d = 0.15 and 0.17 in the main and primary replication NHRVS samples, respectively) and PTSD (d = 0.31 and 0.17, respectively) were independently associated with lower cognitive functioning. ε4 carriers with PTSD scored lower than those without PTSD (d = 0.68 and 1.29, respectively) with the most pronounced differences in executive function (d's = 0.75–1.50) and attention/concentration (d's = 0.62–1.33). A significant interaction was also observed in the Yale–Penn sample, with ε4 carriers with PTSD making more perseverative errors on a measure of executive function than those without PTSD (24.7% vs. 17.6%; d = 0.59). Conclusions: APOE ε4 allele carriers with PTSD have substantially greater cognitive difficulties than ε4 carriers without PTSD. These results underscore the importance of assessing, monitoring, and treating PTSD in trauma-affected individuals who are at genetic risk for cognitive decline and dementia.",
keywords = "APOE, PTSD, aging, cognitive decline, genetics, veterans",
author = "Averill, {Lynnette A.} and Abdallah, {Chadi G.} and Levey, {Daniel F.} and Shizhong Han and Ilan Harpaz-Rotem and Kranzler, {Henry R.} and Southwick, {Steven M.} and Krystal, {John H.} and Joel Gelernter and Pietrzak, {Robert H.}",
note = "Funding Information: The U.S. Department of Veteran Affairs supported this work through its support of the VA National Center for PTSD and the Consortium to Alleviate PTSD. JHK received additional support from a National Institute on Alcohol Abuse and Alcoholism grant (2P50AA012870-14) and National Center for Advancing Translational Science grants (UL1RR024139, principal investigator: R. Sherwin; UH2TR000960, principal investigator: JHK). LAA received support from the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Clinical Research Award, Department of Veterans Affairs VISN 1 Career Development Award, the Brain and Behavior Foundation/NARSAD, and the American Foundation for Suicide Prevention. JHK reports grants from U.S. Department of Veterans Affairs, VA National Center for PTSD and the Consortium to Alleviate PTSD, during the conduct of the study; grants from NIAAA Center for Translational Neuroscience on Alcoholism, grants from National Center for Advancing Translational Science Grants, other from Astra Zeneca Pharmaceuticals, other from Biogen, Idec, MA, other from Biomedisyn Corporation, other from Bionomics Limited (Australia), other from Boehringer Ingelheim International, other from Concert Pharmaceuticals Inc., other from Epiodyne Inc., other from Heptares Therapeutics Limited (UK), other from Janssen Research & Development, other from L.E.K. Consulting, other from Otsuka America Pharmaceutical Inc., other from Perception Neuroscience Holdings Inc., other from Spring Care Inc., other from Sunovion Pharmaceuticals Inc., other from Takeda Industries, other from Taisho Pharmaceuticals Co. Ltd., other from Bioasis Technologies Inc., other from Biohaven Pharmaceuticals, other from BioXcel Therapeutics Inc., other from PsychoGenics Inc., from Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, other from Lohocla Research Corporation, other from ArRETT Neuroscience Inc., other from BlackThorn Therapeutics Inc., other from Storm Biosciences Inc., outside the submitted work. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = sep,
day = "1",
doi = "10.1002/da.22912",
language = "English (US)",
volume = "36",
pages = "834--845",
journal = "Depression and anxiety",
issn = "1091-4269",
publisher = "Wiley-Blackwell",
number = "9",
}