Oxytocin receptor DNA methylation in postpartum depression.
The oxytocin receptor (OXTR) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR. Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P=0.014) with PPD in an intronic region in the OXTR located 4bp proximal to an estrogen receptor (ER) binding region. Pyrosequencing confirmed moderate evidence for an interaction of CpGs in the region with childhood abuse status to mediate PPD. These CpGs located on chr3 at positions 8810078 and 8810069 exhibited significant associations with postpartum depression scores from an independent cohort of 240 women with no prior psychiatric history. Hormone analysis suggested a PPD specific negative correlation of DNA methylation in the region with serum estradiol levels. Estradiol levels and OXTR DNA methylation exhibited a significant interaction to associate with the ratio of allopregnanolone to progesterone. Cumulatively, the data corroborate our previous hypotheses of a PPD specific increased sensitivity of epigenetic reprogramming at estrogen target genes and suggests that OXTR epigenetic variation may be an important mediator of mood relevant neuroactive steroid production.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Psychiatry, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
Mary
M
Kimmel
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Makena
M
Clive
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Fiona
F
Gispen
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jerry
J
Guintivano
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Tori
T
Brown
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Olivia
O
Cox
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Matthias W
MW
Beckmann
Department of Psychiatry, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Johannes
J
Kornhuber
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Peter A
PA
Fasching
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Lauren M
LM
Osborne
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany.
Elisabeth
E
Binder
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jennifer L
JL
Payne
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: zkamins1@jhmi.edu.
Zachary
Z
Kaminsky
D000328:Adult; D001007:Anxiety / Q000235:genetics; D001008:Anxiety Disorders / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics; D019052:Depression, Postpartum / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D004958:Estradiol / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D011280:Pregnanolone; D011374:Progesterone; D011446:Prospective Studies; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism
D018045:Receptors, Oxytocin; D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone
Allopregnanolone; DNA methylation; Estradiol; OXTR; Postpartum depression; Trauma