Evidence for oestrogen sensitivity in perinatal depression: pharmacological sex hormone manipulation study
Research output: Contribution to journal › Journal article › Research › peer-review
BACKGROUND: Enhanced sensitivity to oestrogen signalling may drive increased risk for depressive symptoms when exposed to peripartum sex-steroid hormone fluctuations.
AIM: Testing if 116 pre-identified sex steroid-responsive transcripts that predicted perinatal depression (PND) translates to a pharmacological model of hormone-induced mood changes.
METHOD: We generated longitudinal, genome-wide gene-expression and DNA-methylation data from 60 women exposed to a gonadotrophin-releasing hormone agonist (GnRHa) or placebo. We used linear mixed-effect models to assess differences between baseline and follow-up for gene expression and DNA methylation in the biphasic ovarian response to GnRHa.
RESULTS: Of the 116 PND-predictive transcripts, a significant (19%) overlap was observed with those differentially expressed post-GnRHa at both early and later follow-up, indicating sustained effects. Similarly, 49% of tested genes were differentially methylated post-GnRHa at the late follow-up. Within the GnRHa group, a large proportion of PND genes were significantly associated (gene expression; DNA methylation) with changes in depressive symptoms (28%; 66%), oestradiol levels (49%; 66%) and neocortex serotonin transporter binding (8%; 45%) between baseline and follow-up.
CONCLUSIONS: Our data bridge clinical PND biomarkers with a pharmacological model of sex hormone-induced mood changes and directly relate oestrogen-induced biological changes with depressive symptoms and associated serotonin-signalling changes. Our data highlight that individual variations in molecular sensitivity to oestrogen associate with susceptibility to hormone-induced mood changes and hold promise for candidate biomarkers.
DECLARATION OF INTEREST: V.G.F. received honorarium for being a speaker for H. Lundbeck A/S. E.B.B. receives research funding from Böhringer Ingelheim to investigate FKBP5 as a potential drug target for depression.
Original language | English |
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Journal | The British Journal of Psychiatry |
Volume | 215 |
Issue number | 3 |
Pages (from-to) | 519-527 |
ISSN | 0007-1250 |
DOIs | |
Publication status | Published - 2019 |
ID: 236510476