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

Abstract

BackgroundDepression 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.MethodsThis 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.ResultsCRHR1 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 < 0.000). Although not statistically significant, women with perinatal depression showed a trend towards higher frequency of self-reported menstrual irregularity.ConclusionsNo evidence was found for the association of any of the genetic markers with perinatal depression in this study cohort. Instead, the possible genetic links were found in women with positive family history of mental illness and menstrual irregularity, suggesting these could be identifying risk markers for women.

Don’t stress about CRF: assessing the translational failures of CRF1antagonists

“…Recently it was reported that a TATGA haplotype combination that includes the above 3 polymorphic loci (rs17689966, rs173365, rs7209436, rs110402, and rs242924) increased the risk for major depression by 68% in a community-based study in South Spain (Ching-Lopez et al 2015). Furthermore, the T allele at CRHR1 rs242941, which forms part of a haplotype that previously had been linked to major depression and antidepressant response (Liu et al 2006; Licinio et al 2004; Liu et al 2007) was linked to family history of mental illness (Tan et al 2015). Smoller recently reviewed genome-wide association studies that implicate CRHR1 genotype X early childhood maltreatment environmental interactions for major depression risk (Smoller 2016).…”

A systematic review investigating if genetic or epigenetic markers are associated with postnatal depression

“…However, a fully powered replication study (N=8340) did not confirm these findings (Stergiakouli 2014) and reported only a weak association, between the SNPs in the CRHR1 gene and both antenatal depression and PND. Further to this, no associations with PND were reported by either Schneider et al (2014) or Tan et al (2015) between haplotypes or SNPs occurring in the FKBP5, NR3C1 and CRHR1 genes. Both of these case-control studies had good sample sizes (N=431 and N=725 respectively).…”

Implications of Polymorphisms in the CRHR1 Gene on the Hypothalamic-Pituitary-Adrenal Axis Functioning in Postpartum Depression

“…While two investigations failed to find associations between peripartum depression and CRHR1 polymorphisms [25,26], a third one found a positive association between the G allele of the CRHR1 SNP rs242939 and depression during both pregnancy and postpartum, but the presence of the T allele of SNP rs242941 was associated only with postpartum depression [27]. In addition, few studies have investigated the associations between CRHR1 polymorphisms and the functioning of the HPA axis.…”