Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

Divya Mehta; Karen Grewen; Brenda Pearson; Shivangi Wani; Leanne Wallace; Anjali K Henders; Elisabeth B Binder; Vibe G Frokjaer; Samantha Meltzer-Brody; Naomi R Wray; Alison M Stuebe

doi:10.1038/s41398-021-01270-5

Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

Transl Psychiatry. 2021 Mar 4;11(1):155. doi: 10.1038/s41398-021-01270-5.

Authors

Divya Mehta¹, Karen Grewen², Brenda Pearson², Shivangi Wani³, Leanne Wallace³, Anjali K Henders³, Elisabeth B Binder^{4

5}, Vibe G Frokjaer^{6

7

8}, Samantha Meltzer-Brody², Naomi R Wray³, Alison M Stuebe^{9

10

11}

Affiliations

¹ Queensland University of Technology (QUT), Centre for Genomics and Personalised Health, Faculty of Health, Institute of Health and Biomedical Innovation, Kelvin Grove, QLD, 4059, Australia. divya.mehta@qut.edu.au.
² Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, 27514, USA.
³ Center for Neurostatistics and Statistical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
⁴ Max Planck Institute of Psychiatry, Munich, 80804, Germany.
⁵ Emory University, Atlanta, GA, 30322, USA.
⁶ Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark.
⁷ Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark.
⁸ Mental Health Services Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark.
⁹ Division of Maternal-Fetal Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 27514, USA.
¹⁰ Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
¹¹ Department of Maternal and Child Health, Carolina Global Breastfeeding Institute, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.

Abstract

Maternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29-53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4-2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Depression, Postpartum* / genetics
Female
Gene Expression
Genome-Wide Association Study
Humans
Postpartum Period
Pregnancy
Pregnancy Trimester, Third
Risk Factors