Evidence for oestrogen sensitivity in perinatal depression: pharmacological sex hormone manipulation study

Rex‐Haffner, Monika; Søndergaard, Helle Bach; Pinborg, Anja; Binder, Elisabeth B.; Frøkjær, Vibe G.

doi:10.1192/bjp.2018.234

Cited by 39 publications

(40 citation statements)

References 26 publications

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“…using GnRH agonist for sex hormone manipulation demonstrated an association between estrogen-related mood change and depression (Mehta et al, 2018). The increased incidence of bipolar disorder in women with hysterectomy could be due to the hormone substitution that is normally prescribed after hysterectomy.…”

Section: Discussionmentioning

confidence: 99%

“…In women, periods of natural hormonal decline, such as premenstruation, postpartum, and perimenopause, have been associated with vulnerability to the onset and recurrence of mood disorders (Steiner, Dunn, & Born, 2003). Studies on oral contraceptives (Skovlund, Mørch, Kessing, & Lidegaard, 2016) and gonadotrophin-releasing hormone (GnRH) agonist (Mehta et al, 2018) showed that sex hormone status may be related to depression and mood change.…”

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confidence: 99%

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Association of hysterectomy with bipolar disorder risk: A population‐based cohort study

et al. 2019

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Background: Hormonal fluctuations may trigger the onset of bipolar disorder. We designed a longitudinal follow-up study to evaluate the association between hysterectomies and bipolar disorder risk. Methods: We conducted a large retrospective cohort study using Taiwan's National Health Insurance Research Database. A total of 4,337 women aged 30 to 50 years who underwent the hysterectomy during 2000-2013 were selected and 17,348 patients without hysterectomy were selected for comparison (1:4 match). Poisson regression analysis was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI). Results: During the follow-up of 7.93 years, 20 participants with hysterectomy and 28 without hysterectomy developed bipolar disorder. Receiving hysterectomy was associated with the risk of developing bipolar disorder (adjusted IRR = 2.80; 95% CI = 2.54-3.09). Women with hysterectomy had a higher risk of bipolar disorder in follow-up durations of <1 year (adjusted IRR = 2.18 with 95% CI = 1.94-1.45) and ≥1 year (adjusted IRR = 2.85 with 95% CI = 2.58-3.15). Endometriosis and Premarin use increased bipolar disorder incidence in the hysterectomy group (adjusted IRR = 3.17 [95% CI = 2.83-3.56] and 4.22 [95% CI = 3.71-4.80], respectively). Conclusion: This study concluded that women with hysterectomy have an increased risk of bipolar disorder. Endometriosis and hormone therapy may add to the risk of bipolar disorder after hysterectomy. Knowledge about how surgical or natural hormonal withdrawal influences mood is fundamental and emphasizes the importance of coordinated psychiatric and gynecological care. K E Y W O R D S bipolar disorder, cohort study, epidemiology, hysterectomy, women

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Association of hysterectomy with bipolar disorder risk: A population‐based cohort study

et al. 2019

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“… and in Mehta et al. . Briefly, genome‐wide gene expression and DNA methylation were assessed on the Illumina HT‐12 v4.0 arrays (Illumina, San Diego, CA, USA) and the Infinium HumanMethylation450K BeadChip (Illumina) respectively.…”

Section: Methodsmentioning

confidence: 99%

“… and in Mehta et al. . Data were analyzed using an established analysis pipeline comprising of custom statistical programs and scripts written in R and Linux.…”

Section: Methodsmentioning

confidence: 99%

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

Mehta

Rex‐Haffner

Søndergaard

et al. 2019

Acta Psychiatr Scand

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Frokjaer VG. Genome-wide gene expression in a pharmacological hormonal transition model and its relation to depressive symptoms.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 gonadotrophinreleasing 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 followup 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 followup (intervention group 9 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-hormoneinduced depressive symptoms. Significant outcomes• These data in a pharmacological model of sex-hormone-induced depressive symptoms highlight an altered peripheral blood transcriptomic and epigenomic landscape.• Gene expression and DNA methylation hold promise as biomarkers to help identify women at high risk for developing depressive episodes in relation to hormonal transitions. Limitations• The study may not have enough power to detect subtle gene expression and DNA methylation changes.• The lack of validation experiments is a caveat.

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Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression

et al. 2023

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ImportanceHormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span.ObjectiveTo determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation.Design, Setting, and ParticipantsThis cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery.ExposuresPrior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication.Main Outcomes and MeasuresCrude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery.ResultsOf 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non–HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]).Conclusions and RelevanceThese findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.

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Evidence for oestrogen sensitivity in perinatal depression: pharmacological sex hormone manipulation study

Cited by 39 publications

References 26 publications

Association of hysterectomy with bipolar disorder risk: A population‐based cohort study

Association of hysterectomy with bipolar disorder risk: A population‐based cohort study

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

Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression

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