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Abstract
Objectives
Depressive symptoms are common during pregnancy and after childbirth. Estrogen levels fluctuate greatly during the course of pregnancy and may contribute to mood instability. The first aim of this case–control study was to investigate whether variants in the two estrogen receptor genes might contribute to the genetic susceptibility to pregnancy-related depression using controls that were screened for postnatal depression. The second aim was to uncover new variants in the two estrogen receptor genes.
Patients and methods
Our study sample comprised 554 control subjects who had Edinburgh Postnatal Depression Scale (EPDS) scores below 7 at postnatal screening, and 159 patients with clinically diagnosed pregnancy-related depression. They were genotyped for four single-nucleotide polymorphisms (SNPs) and a dinucleotide repeat in the two genes: estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Fifty-six cases with personal and/or family history of depression of psychiatric disorders were selected for resequencing of the two genes.
Results
There was no statistically significant association with perinatal depression for all five variants. However, there was a trend toward higher frequencies of the genotypes associated with higher risk of depression for rs2077647 and rs4986938 in the case group. From resequencing, two novel ESR1 variants were identified from two different patients.
Conclusion
Our study that used screened controls with low EPDS scores and cases with clinically diagnosed pregnancy-related depression could not replicate the association with depression for any of the SNPs for both genotype and allele frequencies. Two novel SNPs were identified and could be further investigated in a larger sample set.
Acknowledgments
This work was supported by project grants NMRCEDG1006, NMRC/CG/006/2013, and NMRC/CG/M003/2017 administered by the Singapore Ministry of Health’s National Medical Research Council. The authors thank all the study participants, and the staff from Department of Psychological Medicine who assisted with the EPDS screening and the collection of saliva samples.
Disclosure
The authors report no conflicts of interest in this work.