Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype |
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| Affiliation: | 1. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany;2. Center for Child and Family Studies, Rommert Casimir Institute for Developmental Psychopathology, Leiden University, Leiden, The Netherlands;3. Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School (MHH), Hannover, Germany;1. Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tianan, Taiwan;2. Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan;3. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;4. Addiction Research Center, National Cheng Kung University, Tainan, Taiwan;5. Department of Nuclear Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;1. Department of Human Development and Family Science, University of Georgia, 305 Sanford Drive, Athens, GA, 30602, USA;2. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, 2001 North Soto Street, Office 302-02, Los Angeles, CA, 90089-9034, USA;3. Center for Family Research, University of Georgia, 1095 College Station Road, Athens, GA, 30602-4527, USA;4. Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle, Suite 4217, Atlanta, GA, 30322, USA;1. The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, NSW, Australia;2. Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia;3. CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia;4. ARCHI, Sydney Medical School Northern, The University of Sydney, NSW, 2006, Australia;5. The University of Sydney, Brain and Mind Centre, Faculty of Medicine and Health, NSW, Australia;6. School of Medical Sciences, University of New South Wales, NSW, Australia;7. School of Psychology, University of Sydney, NSW, Australia;8. School of Psychology, University of New South Wales, NSW, Australia;9. NSW Health, Northern Sydney Local Health District, Royal North Shore Hospital, St Leonards, NSW, Australia;2. University of Virginia, Department of Psychology, 102 Gilmer Hall, P.O. Box 400400, Charlottesville VA, 22904, United States;3. Duke University, Duke Molecular Physiology Institute, 300 N Duke St, Durham, NC, 27701, United States;4. University of California, Davis, Department of Psychology, One Shields Ave, Davis, CA, 95616, United States;1. Department of Psychiatry, University of Münster, Münster;2. Department of Psychiatry, University of Marburg, Marburg;3. Department of Clinical Radiology, University of Münster, Münster;4. Department of Psychosomatics and Psychotherapy, University of Leipzig, Leipzig;5. Department of Psychiatry, University of Würzburg, Würzburg;6. Department of Psychology, University of Münster, Münster;7. Department of Psychology, University Medical Center, University of Freiburg, Freiburg, Germany;8. Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany;9. Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia;1. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China;2. Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi’an 710069, China;3. College of Education and Sports, Bohai University, Jinzhou 121013, China;4. Research Center for Brain Function and Psychological Science, Shenzhen University, Shenzhen 518060, China;5. Center for Brain and Cognitive Sciences and School of Psychological and Cognitive Sciences, Peking University, Beijing 100871, China;6. Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing 100871, China;7. PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China |
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| Abstract: | The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects – mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed. |
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| Keywords: | Oxytocin Methylation Depression OXTR Biomarkers Exon-specific |
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