Erika J Wolf1, Danielle R Miller2, Mark W Logue3, Jennifer Sumner4, Tawni B Stoop5, Elizabeth C Leritz6, Jasmeet P Hayes7, Annjanette Stone8, Steven A Schichman8, Regina E McGlinchey9, William P Milberg9, Mark W Miller2. 1. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States. Electronic address: erika.wolf@va.gov. 2. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States. 3. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States; Biomedical Genetics, Boston University School of Medicine, Boston, MA, United States; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States. 4. Center for Behavioral Cardiovascular Health, Columbia University Medical Center, NY, NY, United States. 5. Research Service, VA Boston Healthcare System, Boston, MA, United States. 6. Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, United States; Geriatric Research Educational and Clinical Center and Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States. 7. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States; Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, United States. 8. Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, United States. 9. Geriatric Research Educational and Clinical Center and Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Abstract
BACKGROUND: Research suggests that posttraumatic stress disorder (PTSD) is associated with metabolic syndrome (MetS) and that PTSD-associated MetS is related to decreased cortical thickness. However, the role of genetic factors in these associations is unclear. This study evaluated contributions of polygenic obesity risk and PTSD to MetS and of MetS and polygenic obesity risk to cortical thickness. METHODS: 196 white, non-Hispanic veterans of the wars in Iraq and Afghanistan underwent clinical diagnostic interviews, physiological assessments, and genome-wide genotyping; 168 also completed magnetic resonance imaging scans. Polygenic risk scores (PRSs) for obesity were calculated from results of a prior genome-wide association study (Speliotes et al., 2010) and PTSD and MetS severity factor scores were obtained. RESULTS: Obesity PRS (β=0.15, p=0.009) and PTSD (β=0.17, p=0.005) predicted MetS and interacted such that the association between PTSD and MetS was stronger in individuals with greater polygenic obesity risk (β=0.13, p=0.02). Whole-brain vertex-wise analyses suggested that obesity PRS interacted with MetS to predict decreased cortical thickness in left rostral middle frontal gyrus (β=-0.40, p<0.001). CONCLUSIONS: Results suggest that PTSD, genetic variability, and MetS are related in a transactional fashion wherein obesity genetic risk increases stress-related metabolic pathology, and compounds the ill health effects of MetS on the brain. Genetic proclivity towards MetS should be considered in PTSD patients when prescribing psychotropic medications with adverse metabolic profiles. Results are consistent with a growing literature suggestive of PTSD-related accelerated aging. Published by Elsevier Inc.
BACKGROUND: Research suggests that posttraumatic stress disorder (PTSD) is associated with metabolic syndrome (MetS) and that PTSD-associated MetS is related to decreased cortical thickness. However, the role of genetic factors in these associations is unclear. This study evaluated contributions of polygenic obesity risk and PTSD to MetS and of MetS and polygenic obesity risk to cortical thickness. METHODS: 196 white, non-Hispanic veterans of the wars in Iraq and Afghanistan underwent clinical diagnostic interviews, physiological assessments, and genome-wide genotyping; 168 also completed magnetic resonance imaging scans. Polygenic risk scores (PRSs) for obesity were calculated from results of a prior genome-wide association study (Speliotes et al., 2010) and PTSD and MetS severity factor scores were obtained. RESULTS:Obesity PRS (β=0.15, p=0.009) and PTSD (β=0.17, p=0.005) predicted MetS and interacted such that the association between PTSD and MetS was stronger in individuals with greater polygenic obesity risk (β=0.13, p=0.02). Whole-brain vertex-wise analyses suggested that obesity PRS interacted with MetS to predict decreased cortical thickness in left rostral middle frontal gyrus (β=-0.40, p<0.001). CONCLUSIONS: Results suggest that PTSD, genetic variability, and MetS are related in a transactional fashion wherein obesity genetic risk increases stress-related metabolic pathology, and compounds the ill health effects of MetS on the brain. Genetic proclivity towards MetS should be considered in PTSDpatients when prescribing psychotropic medications with adverse metabolic profiles. Results are consistent with a growing literature suggestive of PTSD-related accelerated aging. Published by Elsevier Inc.
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: J A Sumner; L E Duncan; E J Wolf; A B Amstadter; D G Baker; J C Beckham; B Gelaye; S Hemmings; N A Kimbrel; M W Logue; V Michopoulos; K S Mitchell; C Nievergelt; A Rothbaum; S Seedat; G Shinozaki; E Vermetten Journal: Psychol Med Date: 2017-04-04 Impact factor: 7.723
Authors: Joanne E Curran; D Reese McKay; Anderson M Winkler; Rene L Olvera; Melanie A Carless; Thomas D Dyer; Jack W Kent; Peter Kochunov; Emma Sprooten; Emma E Knowles; Anthony G Comuzzie; Peter T Fox; Laura Almasy; Ravindranath Duggirala; John Blangero; David C Glahn Journal: Hum Hered Date: 2013-09-27 Impact factor: 0.444
Authors: Erika J Wolf; Mark W Logue; Jasmeet P Hayes; Naomi Sadeh; Steven A Schichman; Annjanette Stone; David H Salat; William Milberg; Regina McGlinchey; Mark W Miller Journal: Psychoneuroendocrinology Date: 2015-09-30 Impact factor: 4.905
Authors: Goncalo R Abecasis; Adam Auton; Lisa D Brooks; Mark A DePristo; Richard M Durbin; Robert E Handsaker; Hyun Min Kang; Gabor T Marth; Gil A McVean Journal: Nature Date: 2012-11-01 Impact factor: 49.962
Authors: F Saverio Bersani; Synthia H Mellon; Daniel Lindqvist; Jee In Kang; Ryan Rampersaud; Pramod Rajaram Somvanshi; Francis J Doyle; Rasha Hammamieh; Marti Jett; Rachel Yehuda; Charles R Marmar; Owen M Wolkowitz Journal: Mil Med Date: 2020-01-07 Impact factor: 1.563
Authors: Patricia C Swart; Leigh L van den Heuvel; Cathryn M Lewis; Soraya Seedat; Sian M J Hemmings Journal: Front Neurosci Date: 2021-06-10 Impact factor: 4.677
Authors: Danielle R Sullivan; Filomene G Morrison; Erika J Wolf; Mark W Logue; Catherine B Fortier; David H Salat; Jennifer R Fonda; Annjanette Stone; Steven Schichman; William Milberg; Regina McGlinchey; Mark W Miller Journal: J Affect Disord Date: 2019-08-19 Impact factor: 6.533
Authors: Mark W Logue; Mark W Miller; Erika J Wolf; Bertrand Russ Huber; Filomene G Morrison; Zhenwei Zhou; Yuanchao Zheng; Alicia K Smith; Nikolaos P Daskalakis; Andrew Ratanatharathorn; Monica Uddin; Caroline M Nievergelt; Allison E Ashley-Koch; Dewleen G Baker; Jean C Beckham; Melanie E Garrett; Marco P Boks; Elbert Geuze; Gerald A Grant; Michael A Hauser; Ronald C Kessler; Nathan A Kimbrel; Adam X Maihofer; Christine E Marx; Xue-Jun Qin; Victoria B Risbrough; Bart P F Rutten; Murray B Stein; Robert J Ursano; Eric Vermetten; Christiaan H Vinkers; Erin B Ware; Annjanette Stone; Steven A Schichman; Regina E McGlinchey; William P Milberg; Jasmeet P Hayes; Mieke Verfaellie Journal: Clin Epigenetics Date: 2020-03-14 Impact factor: 6.551
Authors: Jennifer A Sumner; Adam X Maihofer; Vasiliki Michopoulos; Alex O Rothbaum; Lynn M Almli; Ole A Andreassen; Allison E Ashley-Koch; Dewleen G Baker; Jean C Beckham; Bekh Bradley; Gerome Breen; Jonathan R I Coleman; Anders M Dale; Michelle F Dennis; Norah C Feeny; Carol E Franz; Melanie E Garrett; Charles F Gillespie; Guia Guffanti; Michael A Hauser; Sian M J Hemmings; Tanja Jovanovic; Nathan A Kimbrel; William S Kremen; Bruce R Lawford; Mark W Logue; Adriana Lori; Michael J Lyons; Jessica Maples-Keller; Matig R Mavissakalian; Regina E McGlinchey; Divya Mehta; Rebecca Mellor; William Milberg; Mark W Miller; Charles Phillip Morris; Matthew S Panizzon; Kerry J Ressler; Victoria B Risbrough; Barbara O Rothbaum; Peter Roy-Byrne; Soraya Seedat; Alicia K Smith; Jennifer S Stevens; Leigh Luella van den Heuvel; Joanne Voisey; Ross McD Young; Lori A Zoellner; Caroline M Nievergelt; Erika J Wolf Journal: Front Neurosci Date: 2021-06-23 Impact factor: 4.677