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Genome‐wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms.

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Title: Genome‐wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms.
Authors: Mehta, D. (AUTHOR), Rex‐Haffner, M. (AUTHOR), Søndergaard, H. B. (AUTHOR), Pinborg, A. (AUTHOR), Binder, E. B. (AUTHOR), Frokjaer, V. G. (AUTHOR)
Source: Acta Psychiatrica Scandinavica. Jul2019, Vol. 140 Issue 1, p77-84. 8p. 1 Color Photograph, 2 Charts.
Subjects: Gene expression, DNA methylation, Serotonin transporters, Focal adhesions, Cytoskeleton
Abstract: 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) were 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 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 × time) after 10% fdr multiple testing correction. Of these, 54% genes were also significantly associated with estradiol changes over time (proxy for GnRHa response magnitude), 9.5% were associated with changes in depressive symptoms, and 38% 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 toward an altered peripheral blood transcriptomic landscape in a pharmacological model of sex‐hormone‐induced depressive symptoms. [ABSTRACT FROM AUTHOR]
Copyright of Acta Psychiatrica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Genome‐wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms.
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  Data: <searchLink fieldCode="AR" term="%22Mehta%2C+D%2E%22">Mehta, D.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rex‐Haffner%2C+M%2E%22">Rex‐Haffner, M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Søndergaard%2C+H%2E+B%2E%22">Søndergaard, H. B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pinborg%2C+A%2E%22">Pinborg, A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Binder%2C+E%2E+B%2E%22">Binder, E. B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Frokjaer%2C+V%2E+G%2E%22">Frokjaer, V. G.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Psychiatrica+Scandinavica%22">Acta Psychiatrica Scandinavica</searchLink>. Jul2019, Vol. 140 Issue 1, p77-84. 8p. 1 Color Photograph, 2 Charts.
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  Data: <searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+methylation%22">DNA methylation</searchLink><br /><searchLink fieldCode="DE" term="%22Serotonin+transporters%22">Serotonin transporters</searchLink><br /><searchLink fieldCode="DE" term="%22Focal+adhesions%22">Focal adhesions</searchLink><br /><searchLink fieldCode="DE" term="%22Cytoskeleton%22">Cytoskeleton</searchLink>
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  Data: 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) were 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 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 × time) after 10% fdr multiple testing correction. Of these, 54% genes were also significantly associated with estradiol changes over time (proxy for GnRHa response magnitude), 9.5% were associated with changes in depressive symptoms, and 38% 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 toward an altered peripheral blood transcriptomic landscape in a pharmacological model of sex‐hormone‐induced depressive symptoms. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Acta Psychiatrica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Jul2019
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