Psychological Medicine

Original Articles

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

D. Mehtaa1 c1, D. J. Newporta2, G. Frishmana3, L. Krausa1, M. Rex-Haffnera1, J. C. Ritchiea4, A. Loria5, B. T. Knighta6, E. Stagnaroa2, A. Rueppa3, Z. N. Stowea6 and E. B. Bindera1a2 c1

a1 Max Planck Institute of Psychiatry, Munich, Germany

a2 Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA

a3 Institute for Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

a4 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

a5 Department of Human Genetics, Emory University, Atlanta, GA, USA

a6 Psychiatry Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA


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.

(Received June 12 2013)

(Revised December 10 2013)

(Accepted December 11 2013)

(Online publication January 31 2014)

Key words

  • Biomarkers;
  • depression;
  • estrogen;
  • postpartum


c1 Address for correspondence: E. B. Binder, M.D., Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich 80804, Germany. (Email: [E. B. Binder] (Email: [D. Mehta]