Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness

Philipp Toepfer; Kieran J O'Donnell; Sonja Entringer; Elika Garg; Christine M Heim; David T S Lin; Julia L MacIsaac; Michael S Kobor; Michael J Meaney; Nadine Provençal; Elisabeth B Binder; Pathik D Wadhwa; Claudia Buss

doi:10.1016/j.psyneuen.2019.01.013

Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness

Psychoneuroendocrinology. 2019 May:103:156-162. doi: 10.1016/j.psyneuen.2019.01.013. Epub 2019 Jan 14.

Authors

Affiliations

¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany.
² Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada; Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, QC, Canada.
³ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany; University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA.
⁴ Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
⁵ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany; Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA.
⁶ Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
⁷ Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada; Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, QC, Canada; Singapore Institute for Clinical Sciences, Singapore.
⁸ Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany; Simon Fraser University, Faculty of Health Sciences, Vancouver, BC, Canada.
⁹ Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
¹⁰ University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA; Departments of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, USA.
¹¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany; University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA. Electronic address: Claudia.buss@charite.de.

Abstract

Maternal behavior (MB) is observable across mammals and represents an important feature of environmental variation during early postnatal development. Oxytocin (OT) plays a crucial role in MB. Even prior to childbirth, pregnancy induces epigenetic and other downstream changes in the maternal OT-system, likely mediated by the actions of steroid hormones. However, little is known about the nature and consequences of epigenetic modifications in the maternal OT-encoding gene (OXT) during pregnancy. Our study aims to investigate temporal dynamics of OXT promoter DNA methylation (DNAm) throughout pregnancy in predicting MB in humans. In 107 mother-child dyads, maternal OXT DNAm was serially analyzed in whole blood in early, mid and late pregnancy. MB was coded based on standardized mother-child interactions at six months postpartum. After controlling for cellular heterogeneity, race/ethnicity, age, and socioeconomic status, OXT-promoter DNAm exhibited a dynamic profile during pregnancy (b = 0.026, t=-3.37, p < .001), with decreases in DNAm from early to mid-pregnancy and no further change until late pregnancy. Moreover, dynamic DNAm trajectories of the OXT-promoter region predicted MB (intrusiveness) at six months postpartum (b = 0.006, t = 2.0, p < 0.05), with 6% higher OXT DNAm in late pregnancy in intrusive compared to non-intrusive mothers. We here demonstrate that OXT promoter DNAm changes significantly throughout gestation in peripheral blood and that these changes are associated with variability in MB, providing a novel potential biomarker predicting postnatal MB.

Keywords: Behavioral epigenetics; DNA methylation; Estrogen sensitivity; Maternal behavior; Oxytocin; Pregnancy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
DNA Methylation*
Depression, Postpartum / blood
Depression, Postpartum / genetics
Epigenesis, Genetic
Female
Humans
Infant, Newborn
Male
Maternal Behavior / physiology*
Mother-Child Relations / psychology
Oxytocin / genetics*
Oxytocin / metabolism
Postpartum Period / genetics
Pregnancy
Promoter Regions, Genetic
Receptors, Oxytocin / genetics
Receptors, Oxytocin / metabolism

Substances

Receptors, Oxytocin
Oxytocin

Abstract

Publication types

MeSH terms

Substances

Grants and funding