Genome-wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms.
Acta Psychiatr Scand. 2019 May 17;:
Authors: Mehta D, Rex-Haffner M, Søndergaard HB, Pinborg A, Binder EB, Frokjaer VG
OBJECTIVES: Sensitivity to sex-steroid hormone fluctuations may increase risk for perinatal depression. We aimed to identify genome-wide biological profiles in women demonstrating sensitivity to pharmacological sex-hormone manipulation with Gonadotrophin Releasing Hormone agonist (GnRHa).
METHODS: Longitudinal gene expression (Illumina Human HT12.v4) and DNA methylation data (Infinium HumanMethylation450K BeadChip) from 60 women (30 GnRHa, 30 placebo) was generated (Trial ID: NCT02661789). Differences between baseline and two follow-up points (initial stimulation and subsequent early suppression phase) in the biphasic ovarian hormone response to GnRHa were assessed in R using linear mixed effects models.
RESULTS: Genome-wide analysis revealed 588 probes differentially expressed from GnRHa intervention to first stimulatory phase follow-up (intervention group x time) after 10% fdr multiple testing correction. Of these, 56% genes were also significantly associated with estradiol changes over time (proxy for GnRHa response magnitude), 11% were associated with changes in depressive symptoms and 41% were associated with changes in neocortical serotonin transporter binding. The genes were implicated in TGF beta Signaling, Adipogenesis, Regulation of Actin Cytoskeleton and Focal Adhesion pathways and enriched for DNA methylation changes (p=0.006).
CONCLUSIONS: These findings point towards an altered peripheral blood transcriptomic landscape in a pharmacological model of sex-hormone-induced depressive symptoms. This article is protected by copyright. All rights reserved.
PMID: 31099405 [PubMed – as supplied by publisher]
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