Oxytocin receptor DNA methylation in postpartum depression

PSYCHONEUROENDOCRINOLOGY

卷:69

Article

Kimmel, Mary^1,6  Clive, Makena¹  Gispen, Fiona¹  Guintivano, Jerry¹  Brown, Tori¹  Cox, Olivia¹  Beckmann, Matthias W.⁴  Kornhuber, Johannes⁵  Fasching, Peter A.⁴  Osborne, Lauren M.¹  Binder, Elisabeth³  Payne, Jennifer L.¹  Kaminsky, Zachary^1,2 

[1] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21287 USA

[3] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany

[4] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany

[5] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Psychiat, D-91054 Erlangen, Germany

[6] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA

关键词: Postpartum depression;    Trauma;    DNA methylation;    OXTR;    Allopregnanolone;    Estradiol;   

DOI  :  10.1016/j.psyneuen.2016.04.008

来源: Elsevier

【 摘 要 】

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 4 bp 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. (C) 2016 Elsevier Ltd. All rights reserved.

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