Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling

D. Mehta, Donald J Newport, G. Frishman, L. Kraus, M. Rex-Haffner, J. C. Ritchie, A. Lori, B. T. Knight, E. Stagnaro, A. Ruepp, Z. N. Stowe, E. B. Binder

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. Method We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. Results We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. Conclusions These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

Original languageEnglish (US)
Pages (from-to)2309-2322
Number of pages14
JournalPsychological Medicine
Volume44
Issue number11
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Postpartum Depression
Estrogen Receptors
Biomarkers
Third Pregnancy Trimester
Gene Expression
Estrogens
Estriol
Genome-Wide Association Study
First Pregnancy Trimester
Psychopathology
Transcriptome
Postpartum Period
Estradiol
Steroids
Mothers
Genome
Hormones

Keywords

  • Biomarkers
  • Depression
  • Estrogen
  • Postpartum

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology

Cite this

Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling. / Mehta, D.; Newport, Donald J; Frishman, G.; Kraus, L.; Rex-Haffner, M.; Ritchie, J. C.; Lori, A.; Knight, B. T.; Stagnaro, E.; Ruepp, A.; Stowe, Z. N.; Binder, E. B.

In: Psychological Medicine, Vol. 44, No. 11, 2014, p. 2309-2322.

Research output: Contribution to journalArticle

Mehta, D, Newport, DJ, Frishman, G, Kraus, L, Rex-Haffner, M, Ritchie, JC, Lori, A, Knight, BT, Stagnaro, E, Ruepp, A, Stowe, ZN & Binder, EB 2014, 'Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling', Psychological Medicine, vol. 44, no. 11, pp. 2309-2322. https://doi.org/10.1017/S0033291713003231
Mehta, D. ; Newport, Donald J ; Frishman, G. ; Kraus, L. ; Rex-Haffner, M. ; Ritchie, J. C. ; Lori, A. ; Knight, B. T. ; Stagnaro, E. ; Ruepp, A. ; Stowe, Z. N. ; Binder, E. B. / Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling. In: Psychological Medicine. 2014 ; Vol. 44, No. 11. pp. 2309-2322.
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AU - Newport, Donald J

AU - Frishman, G.

AU - Kraus, L.

AU - Rex-Haffner, M.

AU - Ritchie, J. C.

AU - Lori, A.

AU - Knight, B. T.

AU - Stagnaro, E.

AU - Ruepp, A.

AU - Stowe, Z. N.

AU - Binder, E. B.

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N2 - Background Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. Method We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. Results We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. Conclusions These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

AB - Background Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. Method We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. Results We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. Conclusions These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

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