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

2018 ◽  
Vol 215 (3) ◽  
pp. 519-527 ◽  
Author(s):  
Divya Mehta ◽  
Monika Rex-Haffner ◽  
Helle Bach Søndergaard ◽  
Anja Pinborg ◽  
Elisabeth B. Binder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Depressive Symptoms ◽  
Perinatal Depression ◽  
Sex Hormone ◽  
Sex Steroid ◽  
Mood Changes ◽  
Induced Mood ◽  
Pharmacological Model

BackgroundEnhanced sensitivity to oestrogen signalling may drive increased risk for depressive symptoms when exposed to peripartum sex-steroid hormone fluctuations.AimTesting if 116 pre-identified sex steroid-responsive transcripts that predicted perinatal depression (PND) translates to a pharmacological model of hormone-induced mood changes.MethodWe 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.ResultsOf 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.ConclusionsOur 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 interestV.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.

BIOM-40. TARGETED GENE EXPRESSION PROFILING PREDICTS MENINGIOMA OUTCOMES AND RADIOTHERAPY RESPONSES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi19-vi20
Author(s):  
William Chen ◽  
Abrar Choudhury ◽  
Harish Vasudevan ◽  
Calixto Lucas ◽  
Minh Nguyen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Validation Cohort ◽  
Postoperative Radiotherapy ◽  
Who Grade ◽  
Targeted Gene Expression ◽  
Methylation Profiling

Abstract BACKGROUND Surgery is the mainstay of meningioma treatment, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. DNA methylation profiling, copy number variants (CNVs), exome sequencing, and RNA sequencing have improved understanding of meningioma biology, but have not superseded histologic grading, or revealed biomarkers for radiotherapy responses. To address these unmet needs, we optimized and validated a targeted gene expression biomarker predicting meningioma outcomes and responses to radiotherapy. METHODS Targeted gene expression profiling was performed on a discovery cohort of 173 meningiomas (median follow-up 8.1 years) and a validation cohort of 331 meningiomas (median follow-up 6.1 years) treated with surgery (n=504) and postoperative radiotherapy (n=73) at independent, international institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). Optimized targeted gene expression models predicting clinical outcomes (34 genes) or radiotherapy responses (12 genes) were developed from the discovery cohort, and compared to histologic and molecular classification systems by performing DNA methylation profiling, CNV analysis, exome sequencing, and RNA sequencing on the same meningiomas. RESULTS Targeted gene expression profiling achieved a concordance-index of 0.75 ± 0.03 (SEM) for local freedom from recurrence (LFFR) and 0.72 ± 0.03 for overall survival (OS) in the validation cohort, outperforming WHO grade (5-year LFFR delta-AUC 0.15, 95% CI 0.076-0.229, p=0.001) and DNA methylation grouping (delta-AUC 0.075, 95% CI 0.006-0.130, p=0.01) for LFFR, disease-specific survival, and OS. The biomarker was independently prognostic after accounting for WHO grade, extent of resection, primary versus recurrent presentation, CNV status, DNA methylation group, and Ki67 labeling index, and identified meningiomas benefiting from radiotherapy (interaction p-value=0.0008), suggesting postoperative radiotherapy could be refined in 30.2% of cases. CONCLUSIONS Targeted gene expression profiling of 504 meningiomas improves discrimination of meningioma local recurrence, disease-specific survival, and overall survival, and predicts radiotherapy responses.

scholarly journals Perinatal Depression and Its Impact on Infant Outcomes and Maternal-Nurse SMS Communication in a Cohort of Kenyan Women

2021 ◽  
Author(s):  
Alyssa Hummel ◽  
Keshet Ronen ◽  
Amritha Bhat ◽  
Brenda Wandika ◽  
Esther M. Choo ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Infant Health ◽  
Perinatal Depression ◽  
Infant Outcomes ◽  
Increased Risk ◽  
Antenatal Depressive Symptoms ◽  
Kenyan Women ◽  
Perinatal Depressive Symptoms ◽  
Prospective Longitudinal

Abstract Background Perinatal depression is broadly defined as depressive symptoms during pregnancy or within the 12 months following delivery, affecting approximately 20-25% of pregnant and postpartum women in low- and middle-income countries. The wide accessibility of mobile phones allows mobile health (mHealth) interventions to be considered a solution to identify perinatal depression and provide appropriate referrals for treatment. This study, nested in a larger SMS communication project, examined the prevalence and correlates of perinatal depression, determined the association between antenatal depression and infant morbidity/mortality, and compared SMS communication patterns between women with and without perinatal depression. Methods This was a prospective longitudinal cohort of pregnant women seeking antenatal services at two public sector health clinics in Kenya. SMS messages were sent to participants with educational content related to their pregnancy and infant health and two-way SMS communication occurred with a nurse. Sociodemographic and obstetric characteristics, SMS messaging behaviors, infant health status, and depressive symptoms were assessed by a standardized questionnaire administered at enrollment (30-36 weeks gestation) and follow-up (14 weeks postpartum). Generalized estimating equation (GEE) with Poisson link was used to evaluate correlates of perinatal depressive symptoms, infant outcomes, and frequency of SMS messaging. Results Of the 572 women with complete follow-up information, 188 (32.9%) screened positive for elevated depressive symptoms (≥10 by EPDS scale) at some time point during pregnancy or postpartum. The strongest predictors of depressive symptoms included abuse during pregnancy, fewer years of schooling, and maternal unemployment. Antenatal depressive symptoms were associated with an increased risk of infant illness or hospitalization (RR = 1.12, 95% CI: 1.11, 1.13). Women with antenatal or persistent perinatal depressive symptoms sent fewer SMS messages during the study period than their counterparts without depression. Conclusions Prevalence of elevated perinatal depressive symptoms was high in this cohort of Kenyan women. Our findings highlight the importance of screening perinatal women for experiences of abuse and symptoms of depression. Differences in messaging frequency between women with vs. without depressive symptoms presents a potential opportunity to provide more support for those perinatal depression.

Cathartic Effect of Suicide Attempts Not Limited to Depression

Crisis ◽  
2003 ◽  
Vol 24 (2) ◽  
pp. 73-78 ◽  
Author(s):  
Yves Sarfati ◽  
Blandine Bouchaud ◽  
Marie-Christine Hardy-Baylé
Keyword(s):  
Quality Of Life ◽  
Depressive Symptoms ◽  
Personality Traits ◽  
Rating Scales ◽  
Suicide Attempts ◽  
World Health ◽  
Life Questionnaire ◽  
Short Term

Summary: The cathartic effect of suicide is traditionally defined as the existence of a rapid, significant, and spontaneous decrease in the depressive symptoms of suicide attempters after the act. This study was designed to investigate short-term variations, following a suicide attempt by self-poisoning, of a number of other variables identified as suicidal risk factors: hopelessness, impulsivity, personality traits, and quality of life. Patients hospitalized less than 24 hours after a deliberate (moderate) overdose were presented with the Montgomery-Asberg Depression and Impulsivity Rating Scales, Hopelessness scale, MMPI and World Health Organization's Quality of Life questionnaire (abbreviated versions). They were also asked to complete the same scales and questionnaires 8 days after discharge. The study involved 39 patients, the average interval between initial and follow-up assessment being 13.5 days. All the scores improved significantly, with the exception of quality of life and three out of the eight personality traits. This finding emphasizes the fact that improvement is not limited to depressive symptoms and enables us to identify the relative importance of each studied variable as a risk factor for attempted suicide. The limitations of the study are discussed as well as in particular the nongeneralizability of the sample and setting.

Characterization of sex hormone binding globulin ligands with potential to enhance sex steroid action

2018 ◽  
Author(s):  
Phillip Round ◽  
Samir Das ◽  
Kristiina Wahala ◽  
Petegem Filip Van ◽  
Geoffrey Hammond
Keyword(s):  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Sex Steroid ◽  
Hormone Binding

DNA Methylation Inhibites ANXA1 Gene Expression in Nasopharyngeal Carcinoma Cell Lines*

2009 ◽  
Vol 36 (10) ◽  
pp. 1319-1326 ◽  
Author(s):  
Shuang-Xiang TAN ◽  
Rui-Cheng HU ◽  
Ai-Guo DAI ◽  
Cen-E TANG ◽  
Hong YI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Nasopharyngeal Carcinoma Cell ◽  
Carcinoma Cell Lines

Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene

Epigenomics ◽  
2020 ◽  
Author(s):  
Alexandra E Dereix ◽  
Rachel Ledyard ◽  
Allyson M Redhunt ◽  
Tessa R Bloomquist ◽  
Kasey JM Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Trait Anxiety ◽  
Cpg Island ◽  
Depression Scale ◽  
Maternal Anxiety ◽  
Anxiety And Depression ◽  
Pregnancy Anxiety ◽  
Glucocorticoid Receptor Gene ◽  
Island Shore

Aim: To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor ( NR3C1). Materials & methods: Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. NR3C1 methylation was determined at four methylation sites. Results: DNA methylation of CpG 1 in the NR3C1 CpG island shore was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49–4.58) and trait anxiety (β 1.68, 95% CI: 0.14–3.22). No significant association was found between depressive symptoms and NR3C1 methylation. Conclusion: We found that maternal anxiety was associated with increased NR3C1 CpG island shore methylation.

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