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.
Highlights
The perinatal period spanning across pregnancy and postpartum is a vulnerable time for increased mental health issues, which presents several challenges for Children who are born to mothers with Postpartum depression (PPD) have poor health outcomes compared to the general population including shorter gestation periods, impaired cardiovascularMehta et al Translational Psychiatry (2021)11:155 functioning, increased gastrointestinal infections, reduced weight gain and lower respiratory tract infections[6,7,8]
We tested if gene expression profiles of women during the third trimester of pregnancy were significantly associated with depressive symptoms at 2 months postpartum
Through negative binomial regression models using the edgeR package in R30, the gene expression profiles were regressed against the quantitative Edinburgh Postnatal Depression Scale (EPDS) scores, with maternal age, ethnicity, gestational age in weeks, current and past medications and psychological treatments and BMI included as covariates
Summary
The perinatal period spanning across pregnancy and postpartum is a vulnerable time for increased mental health issues, which presents several challenges for Children who are born to mothers with PPD have poor health outcomes compared to the general population including shorter gestation periods, impaired cardiovascularMehta et al Translational Psychiatry (2021)11:155 functioning, increased gastrointestinal infections, reduced weight gain and lower respiratory tract infections[6,7,8]. PPD is associated with a range of cascading long-term negative health outcomes for the mother and infant including an increased risk of psychiatric disorders and neurodevelopmental deficits such as behavioural problems and learning difficulties in the offspring[9,10,11] and perturbed immune system in mothers and maternal suicide[12]. Several studies suggest that screening early on in pregnancy can reduce anxiety or depressive symptoms; there is very little research and intervention for primary prevention[14,15]. Potential causes for PPD include psychosocial factors such as a history of depression or a psychiatric disorder during pregnancy, inadequate social support, emotional isolation, financial strain, stressful life events and biological factors such as genetic risk and sensitivity to hormonal changes have been proposed[16,17,18]
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