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Postpartum depression, Trauma, DNA methylation, OXTR, Allopregnanolone, Estradiol
Abstract:
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.
