Natalie P Mota1, Shizhong Han2, Ilan Harpaz-Rotem3,4, Paul Maruff5, John H Krystal3,4, Steven M Southwick3,4, Joel Gelernter3,4, Robert H Pietrzak3,4. 1. Department of Clinical Health Psychology, Max Rady College of Medicine, University of Manitoba, Manitoba, Canada. 2. Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA. 3. Clinical Neurosciences Division, U.S. Department of Veterans Affairs National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA. 4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. 5. Florey Institute of Neuroscience and Mental Health, University of Melbourne and Cogstate, Ltd., Melbourne, Australia.
Abstract
BACKGROUND: Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011. The independent replication sample consisted of 509 trauma-exposed EA veterans from the 2013 NHRVS. RESULTS: APOE ε4 allele carriers reported significantly greater severity of PTSD symptoms than noncarriers in the main, but not the replication, sample. In both samples, the interaction of APOE ε4 carrier status and cumulative trauma burden was associated with greater severity of PTSD symptoms (F range = 2.53-8.09, all P's < .01), particularly re-experiencing/intrusion symptoms (F range = 3.59-4.24, P's < .001). Greater social support was associated with lower severity of PTSD symptoms among APOE ε4 allele carriers with greater cumulative trauma burden (β range -.27 to -.60, P's < .05). CONCLUSION: U.S. military veterans who are APOE ε4 allele carriers and exposed to a high number of traumas may be at increased risk for developing PTSD symptoms than ε4 noncarriers. Greater social support may moderate this association, thereby highlighting the potential importance of social support promoting interventions in mitigating the effect of ε4 × cumulative trauma burden on PTSD risk.
BACKGROUND: Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011. The independent replication sample consisted of 509 trauma-exposed EA veterans from the 2013 NHRVS. RESULTS:APOE ε4 allele carriers reported significantly greater severity of PTSD symptoms than noncarriers in the main, but not the replication, sample. In both samples, the interaction of APOE ε4 carrier status and cumulative trauma burden was associated with greater severity of PTSD symptoms (F range = 2.53-8.09, all P's < .01), particularly re-experiencing/intrusion symptoms (F range = 3.59-4.24, P's < .001). Greater social support was associated with lower severity of PTSD symptoms among APOE ε4 allele carriers with greater cumulative trauma burden (β range -.27 to -.60, P's < .05). CONCLUSION: U.S. military veterans who are APOE ε4 allele carriers and exposed to a high number of traumas may be at increased risk for developing PTSD symptoms than ε4 noncarriers. Greater social support may moderate this association, thereby highlighting the potential importance of social support promoting interventions in mitigating the effect of ε4 × cumulative trauma burden on PTSD risk.
Authors: Alkes L Price; Nick J Patterson; Robert M Plenge; Michael E Weinblatt; Nancy A Shadick; David Reich Journal: Nat Genet Date: 2006-07-23 Impact factor: 38.330
Authors: Bernet M Elzinga; Karin Roelofs; Marieke S Tollenaar; Patricia Bakvis; Johannes van Pelt; Philip Spinhoven Journal: Psychoneuroendocrinology Date: 2007-12-21 Impact factor: 4.905
Authors: Dean G Kilpatrick; Karestan C Koenen; Kenneth J Ruggiero; Ron Acierno; Sandro Galea; Heidi S Resnick; John Roitzsch; John Boyle; Joel Gelernter Journal: Am J Psychiatry Date: 2007-11 Impact factor: 18.112
Authors: Brienna M Fogle; Jack Tsai; Natalie Mota; Ilan Harpaz-Rotem; John H Krystal; Steven M Southwick; Robert H Pietrzak Journal: Front Psychiatry Date: 2020-12-09 Impact factor: 4.157
Authors: Murray B Stein; Karmel W Choi; Sonia Jain; Laura Campbell-Sills; Chia-Yen Chen; Joel Gelernter; Feng He; Steven G Heeringa; Adam X Maihofer; Caroline Nievergelt; Matthew K Nock; Stephan Ripke; Xiaoying Sun; Ronald C Kessler; Jordan W Smoller; Robert J Ursano Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-05-13 Impact factor: 3.568
Authors: Irina L Kuznetsova; Natalya V Ponomareva; Ekaterina A Alemastseva; Andrey D Manakhov; Tatyana V Andreeva; Fedor E Gusev; Evgeny I Rogaev Journal: Genes (Basel) Date: 2022-01-18 Impact factor: 4.096
Authors: Karen A Lawrence; Theresia M Pachner; Molly M Long; Stephanie Henderson; Donna L Schuman; Brenda L Plassman Journal: BMJ Open Date: 2020-06-03 Impact factor: 2.692
Authors: D Parker Kelley; Ardalan Chaichi; Alexander Duplooy; Dhirendra Singh; Manas Ranjan Gartia; Joseph Francis Journal: Neurobiol Stress Date: 2022-08-11
Authors: 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 Journal: Front Physiol Date: 2020-01-31 Impact factor: 4.566