TY - JOUR
T1 - ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations
AU - Johnson, Lance A.
AU - Zuloaga, Damian G.
AU - Bidiman, Erin
AU - Marzulla, Tessa
AU - Weber, Sydney
AU - Wahbeh, Helane
AU - Raber, Jacob
N1 - Funding Information:
LAJ was supported by NIEHS Grant T32-ES07060, NIH Grant T32-HL094294, and NSF Postdoctoral Fellowship SMA-1408653. HW was supported by NIH Grant K01AT004951.The content of this manuscript is solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NSF. EB was supported by a Miller Fellowship through Lewis and Clark College, Portland, OR. The authors declare no conflict of interest.
Publisher Copyright:
© 2015 American College of Neuropsychopharmacology. All rights reserved.
PY - 2015/9/14
Y1 - 2015/9/14
N2 - Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.
AB - Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.
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U2 - 10.1038/npp.2015.95
DO - 10.1038/npp.2015.95
M3 - Article
C2 - 25857685
AN - SCOPUS:84939260016
VL - 40
SP - 2443
EP - 2453
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 10
ER -