Archives of Women's Mental Health

, Volume 16, Issue 6, pp 499–509 | Cite as

Association study of the estrogen receptor gene ESR1 with postpartum depression—a pilot study

  • Julia K. Pinsonneault
  • Danielle Sullivan
  • Wolfgang Sadee
  • Claudio N. Soares
  • Elizabeth Hampson
  • Meir Steiner
Original Article


Perinatal mood disorders, such as postpartum depression (PPD), are costly for society, with potentially serious consequences for mother and child. While multiple genes appear to play a role in PPD susceptibility, the contributions of specific genetic variations remain unclear. Previously implicated as a candidate gene, the estrogen receptor alpha gene (ESR1) is a key player in mediating hormonal differences during pregnancy and the postpartum period. This study addresses genetic factors in perinatal mood disorders, testing nine polymorphisms in ESR1. Two hundred fifty-seven postpartum women were screened for mood disorders, including 52 women with PPD and 32 without any symptoms of mood disorders. We detected a significant association for the upstream TA microsatellite repeat with Edinburgh Postnatal Depression Scale scores (p = 0.007). The same variant was also associated with the occurrence of PPD. Separately, 11 candidate functional polymorphisms in 7 additional genes were genotyped to investigate gene–gene interaction with the ESR1 TA repeat, identifying a potential interaction with the serotonin transporter. Our results support a role for ESR1 in the etiology of PPD, possibly through the modulation of serotonin signaling. Our findings for ESR1 could have broad implications for other disorders and therapies that involve estrogens.


Postpartum depression Edinburgh postnatal depression scale ESR1 estrogen receptor Genetic variation SNP 

List of abbreviations


postpartum depression


single nucleotide polymorphism


linkage disequilibrium


minor allele frequency


Montgomery–Asberg Depression Rating Scale


Edinburgh Postnatal Depression Scale


Stuctured Clinical Interview for DSM Disorders


Mini International Neuropsychiatric Interview


Major depressive disorder


Generalized anxiety disorder



The authors are grateful to Audrey Papp, Gloria Smith, and Marg Coote for preparation of DNA specimens. This study was supported by a pilot award from the Society for Women’s Health Research Isis Fund Network (WS, MS, EH and JP), and the National Institutes of Health U01 GM092655 (WS). EH holds a Senior Career Research Chair in Women’s Health from the Canadian Institutes of Health Research.

Conflict of interests

The authors declare that they have no competing interests.

Supplementary material

737_2013_373_MOESM1_ESM.pdf (140 kb)
Figure S1 A): A histogram of EPDS score distribution.): The Q-Q plot of linear regression with ‘EPDS’ as the outcome. All residuals appeared fine (plots C and D), and any log-transform of the outcome made the residuals significantly worse. C): A Q-Q plot for the residuals from the interaction model showing that normality is not violated. D): Residuals vs. fitted values demonstrating that the assumption of constant variance is not violated, and they also appear, for the most part, centered at zero. All model assumptions appear satisfied. (PDF 139 kb)
737_2013_373_MOESM2_ESM.pdf (27 kb)
Table S1 Genes represented by SNP genotyping in our analysis. (PDF 26 kb)
737_2013_373_MOESM3_ESM.pdf (23 kb)
Table S2 Genotyping primers for non-ESR1 variants except COMT rs4680, which was genotyped with a commercially available TaqMan assay (Life Technologies). (PDF 24 kb) (PDF 23 kb)
737_2013_373_MOESM4_ESM.pdf (23 kb)
Table S3 Additional SNP information (PDF 22 kb)
737_2013_373_MOESM5_ESM.pdf (24 kb)
Table S4 Genetic association summary of functional polymorphisms in the additional seven candidate genes with EPDS score. (PDF 24 kb)


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Julia K. Pinsonneault
    • 1
  • Danielle Sullivan
    • 1
    • 2
  • Wolfgang Sadee
    • 1
  • Claudio N. Soares
    • 3
  • Elizabeth Hampson
    • 4
  • Meir Steiner
    • 3
  1. 1.Department of Pharmacology and Program in PharmacogenomicsThe Ohio State University College of MedicineColumbusUSA
  2. 2.The Department of Biostatistics, College of Public HealthThe Ohio State UniversityColumbusUSA
  3. 3.Women’s Health Concerns Clinic, St. Joseph’s Healthcare, Department of Psychiatry & Behavioral Neurosciences and Obstetrics & GynecologyMcMaster UniversityHamiltonCanada
  4. 4.Department of Psychology and Graduate Program in NeuroscienceUniversity of Western OntarioLondonCanada

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