Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape
| Autor: | Anjali K. Henders, Divya Mehta, Samantha Meltzer-Brody, Vibe G. Frokjaer, Alison M. Stuebe, Elisabeth B. Binder, Brenda Pearson, Karen M. Grewen, Naomi R. Wray, Shivangi Wani, Leanne Wallace |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Postpartum depression
Pregnancy Trimester Third Gene Expression Physiology MMP8 Article lcsh:RC321-571 Depression Postpartum Cellular and Molecular Neuroscience Pregnancy Risk Factors medicine Humans Child lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Gene Biological Psychiatry Depression (differential diagnoses) Depression business.industry Comparative genomics Postpartum Period medicine.disease Phenotype Psychiatry and Mental health Edinburgh Postnatal Depression Scale Cohort Female business Genome-Wide Association Study |
| Zdroj: | Mehta, D, Grewen, K, Pearson, B, Wani, S, Wallace, L, Henders, A K, Binder, E B, Frokjaer, V G, Meltzer-Brody, S, Wray, N R & Stuebe, A M 2021, ' Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape ', Translational Psychiatry, vol. 11, no. 1, 155 . https://doi.org/10.1038/s41398-021-01270-5 Translational Psychiatry, Vol 11, Iss 1, Pp 1-16 (2021) Translational Psychiatry |
| DOI: | 10.1038/s41398-021-01270-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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