@article{be0c1e515bdd4930a1306e3df6f2fb9c,
title = "Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress",
abstract = "Background: Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression. Methods: In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples. Results: A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues. Conclusions: These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders.",
keywords = "Anxiety, DASS scale, Depression, Oxytocin, RNA expression, SNP, Stress",
author = "Myers, {Amanda J.} and Leanne Williams and Gatt, {Justine M.} and McAuley-Clark, {Erica Z.} and Carol Dobson-Stone and Schofield, {Peter R.} and Nemeroff, {Charles B.}",
note = "Funding Information: AJM is supported by NIA AG041232 and NIMH MH094759 . This project was supported by an Australian Research Council Linkage Project grant (LP0455104) held by LMW and with Brain Resource Ltd as the industry partner. JMG is supported by the National Health & Medical Research Council of Australia (NHMRC) Career Development Fellowship APP 1062495 . CDS is supported by the National Health & Medical Research Council of Australia (NHMRC) Project Grant 630428 . PRS is supported by NHMRC Program Grant 1037196 . CBN is supported by NIMH MH094759 . We acknowledge access to data from the 501(c)(3) BRAINnet Foundation database; www.BRAINnet.net . LMW is CEO and Director of the BRAINnet Foundation. Funding Information: Brain tissue specimens for the expression studies were collected from several National Institute on Aging (NIA) and National Alzheimer's Coordinating Center (NACC , grant # U01 AG016976 ) funded sites. Amanda J. Myers, PhD (University of Miami, Department of Psychiatry) and John A. Hardy, PhD (Reta Lila Weston Institute, University College London) collected and prepared the series. Marcelle Morrison-Bogorad, PhD., Tony Phelps, PhD and Walter Kukull PhD are thanked for helping to co-ordinate this collection. The directors, pathologist and technicians involved include: National Institute on Aging: Ruth Seemann, John Hopkins Alzheimer's Disease Research Center (NIA grant # AG05146): Juan C. Troncoso, MD, Dr. Olga Pletnikova, University of California, Los Angeles (NIA grant #P50 AG16570):Harry Vinters, MD, Justine Pomakian, The Kathleen Price Bryan Brain Bank, Duke University Medical Center (NIA grant #AG05128, NINDS grant # NS39764, NIMH MH60451 also funded by Glaxo Smith Kline): Christine Hulette, MD, Director, John F. Ervin, Stanford University: Dikran Horoupian, MD, Ahmad Salehi, MD, PhD, New York Brain Bank, Taub Institute, Columbia University (NYBB): Jean Paul Vonsattel, MD, Katerina Mancevska, Massachusetts Alzheimer's Disease Research Center (P50 AG005134): E. Tessa Hedley-Whyte, MD, MP Frosch, MD, Karlotta Fitch, University of Michigan (NIH grant P50-AG08671): Dr. Roger Albin, Lisa Bain, Eszter Gombosi, University of Kentucky (NIH #AG05144): William Markesbery, MD, Sonya Anderson, Mayo Clinic, Jacksonville: Dennis W. Dickson, MD, Natalie Thomas, University Southern California: Caroll A. Miller, MD, Jenny Tang, M.S., Dimitri Diaz, Washington University, St Louis Alzheimer's Disease Research Center (NIH #P50AG05681): Dan McKeel, MD, John C. Morris, MD, Eugene Johnson, Jr., PhD, Virginia Buckles, PhD, Deborah Carter, University of Washington, Seattle (NIH #P50 AG05136):Thomas Montine, MD, PhD, Aimee Schantz, MEd., University of Pennsylvania School of Medicine, Alzheimer's Disease Research Center: John Q Trojanowski, MD, Virginia M Lee, MD, Vivianna Van Deerlin, MD, Terry Schuck, Boston University Alzheimer's Disease Research Center (NIH grant P30-AG13846): Ann C. McKee, Carol Kubilus Sun Health Research Institute Brain Donation Program of Sun City, Arizona (NIA #P30 AG19610; Arizona Alzheimer's Disease Core Center, Arizona Department of Health Services, contract 211002, Arizona Alzheimer's Research Center; Arizona Biomedical Research Commission, contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium; Michael J. Fox Foundation for Parkinson's Research): Joseph Rogers, PhD, Thomas G. Beach, MD, PhD, Lucia I. Sue Emory University: Bruce H. Wainer, MD, PhD, Marla Gearing, PhD, University of Texas, Southwestern Medical School: Charles L. White, III, M.D., Roger Rosenberg, Marilyn Howell, Joan Reisch, University of California, Davis: William Ellis, MD, Mary Ann Jarvis, Rush University Medical Center, Rush Alzheimer's Disease Center (NIH #AG10161): David A. Bennett, M.D. Julie A. Schneider, MD, MS, Karen Skish, MS, PA (ASCP)MT, Wayne T Longman, University of Miami/NPF Brain Endowment Bank: Deborah C. Mash, MD, Margaret J Basile, Mitsuko Tanaka Oregon Health & Science University: Randy Wotljer, PhD. Funding Information: Additional tissues include samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council , local NHS trusts and Newcastle University ): C.M. Morris, MD, Ian G McKeith, Robert H Perry MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council): Simon Lovestone, Md PhD, Safa Al-Sarraj. MD, Claire Troakes, South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE) , Alzheimer's Research Trust (ART) , BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN ): Seth Love, MD, Patrick Kehoe, PhD, Laura Palmer, The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek): Inge Huitinga, MD, Marleen Rademaker, Michiel Kooreman, Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona: Isidre Ferrer Abizanda, MD, PhD, Susana Casas Boluda. Funding Information: Genotyping was sponsored by an Australian Research Council Linkage Project grant ( LP0455104 ) with Brain Resource Ltd as the industry partner. Data analysis was supported by NIA AG041232 and NIMH MH094759. Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",
year = "2014",
month = dec,
day = "1",
doi = "10.1016/j.jpsychires.2014.08.021",
language = "English (US)",
volume = "59",
pages = "93--100",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",
}
