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Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression.

ABSTRACT: Depression during pregnancy or after childbirth is the most frequent perinatal illness affecting women of reproductive age. It could result in unfavourable outcomes for both women and their newborns. The incidence of perinatal depression is higher for those with family history of depression and other mental illness, suggesting the contribution of genetic factors. There is postulation that disruption or fluctuation of reproductive hormones could play a part in women who are sensitive to such changes.This is a case-control study comparing the frequencies of candidate gene variants in patients with perinatal depression with controls. Patients of Chinese descent (N?=?725) were recruited from the outpatient clinics of the hospital between 2010 and 2013. Controls were patients who came for postnatal consultations at the obstetrics clinics and scored???7 on the Edinburgh Postnatal Depression Scale (EPDS) at the postnatal screening programme of the hospital. Cases with confirmed diagnosis of clinical (major) depression related to pregnancy/postpartum were recruited from the hospital's outpatient clinic. Genomic DNA was extracted from saliva samples and genotyped for the polymorphisms of interest. Differences between groups were assessed by chi-square analysis.CRHR1 rs242939 and rs1876828 were not polymorphic in the study population. There was no statistically significant association of perinatal depression for CRHR1 rs242941 and GR rs41423247 (BclI). When all subjects were grouped based on family history of mental illness, there was a statistically significant association of CRHR1 rs242941 with family history regardless of depression status (P?=?0.043). There was also a statistically significant difference for GR rs41423247 and regularity of menstrual periods (P?

SUBMITTER: Tan EC

PROVIDER: S-EPMC4628323 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression.

Tan Ene-Choo EC Chua Tze-Ern TE Lee Theresa M Y TM Tan Hui-San HS Ting Joe L Y JL Chen Helen Y HY

BMC pregnancy and childbirth 20151030

<h4>Background</h4>Depression during pregnancy or after childbirth is the most frequent perinatal illness affecting women of reproductive age. It could result in unfavourable outcomes for both women and their newborns. The incidence of perinatal depression is higher for those with family history of depression and other mental illness, suggesting the contribution of genetic factors. There is postulation that disruption or fluctuation of reproductive hormones could play a part in women who are sen ...[more]

PMID: 26518448

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Project description:Corticotropin-releasing hormone (CRH) plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and regulates the stress response through two CRH receptors (R1 and R2). Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436) and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs) of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220) were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017) and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS), and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710) and two SNPs (rs2284217 and rs2284220) in strong linkage disequilibrium (D' > 0.90). We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH system are warranted.

Project description:ContextGenetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression.ObjectiveTo examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene.DesignAssociation study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.SettingGeneral medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.ParticipantsThe primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished).Main outcome measuresBeck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders.ResultsFifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199).ConclusionsThese data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

Dataset Information

Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression.

Publications

Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression.

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