Evidence for oestrogen sensitivity in perinatal depression: pharmacological sex hormone manipulation study. (September 2019)

• Record Type: Journal Article
• Authors: Mehta, Divya; Rex-Haffner, Monika; Søndergaard, Helle Bach; Pinborg, Anja; Binder, Elisabeth B.; Frokjaer, Vibe G.
• Is Part Of: British journal of psychiatry. Volume 215:Number 3(2019)
• Page Start: 519
• Page End: 527
• Publication Date: 2019-09
• Subjects: Perinatal depression, -- biomarkers, -- oestrogen, -- gene expression, -- DNA methylation; Psychiatry -- Periodicals; Psychology, Pathological -- Periodicals; 616.89005
• DOI: 10.1192/bjp.2018.234
• Languages: English
• ISSNs: 0007-1250

Abstract

Abstract : 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.