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


METHODS
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.
Max Planck Institute of Psychiatry, Munich,Germany.
D
D
Mehta
Emory University School of Medicine,Department of Psychiatry and Behavioral Sciences, Atlanta, GA,USA.
D J
DJ
Newport
Institute for Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg,Germany.
G
G
Frishman
Max Planck Institute of Psychiatry, Munich,Germany.
L
L
Kraus
Max Planck Institute of Psychiatry, Munich,Germany.
M
M
Rex-Haffner
Department of Pathology and Laboratory Medicine,Emory University,Atlanta, GA,USA.
J C
JC
Ritchie
Department of Human Genetics,Emory University,Atlanta, GA,USA.
A
A
Lori
Psychiatry Research Institute,University of Arkansas for Medical Sciences,Little Rock, AR,USA.
B T
BT
Knight
Emory University School of Medicine,Department of Psychiatry and Behavioral Sciences, Atlanta, GA,USA.
E
E
Stagnaro
Institute for Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg,Germany.
A
A
Ruepp
Psychiatry Research Institute,University of Arkansas for Medical Sciences,Little Rock, AR,USA.
Z N
ZN
Stowe
Max Planck Institute of Psychiatry, Munich,Germany.
E B
EB
Binder
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019052:Depression, Postpartum / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology*
D015415:Biomarkers