Inflammatory modulation in pregnancy and postpartum period as a risk factor for perinatal depression

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The link between maternal inflammatory dysregulation and perinatal depression remains poorly understood. Mice models have identified estrogen loss as an activator of memory T cells leading to persistent secretion of proinflammatory cytokines. The objective of this study was to evaluate the relationship between the maternal inflammatory milieu in pregnancy and postpartum and risk of perinatal depression. We conducted a prospective observational study of pregnant and postpartum women who received their obstetric care at a tertiary academic medical center between November 2021 to May 2022. Serum specimens were collected from women with a singleton gestation in the 3rd trimester of pregnancy at 2 time points – at recruitment and 4-8 weeks postpartum. Risk for antepartum and postpartum depression were evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each time point. Serum cytokines including IFN-γ, IL1-β, IL-4, IL-6, IL-7, IL-10, IL-15, IL-17A and TNF-α were measured in prenatal and postnatal specimens using a Luminex multiplex assay and correlated with corresponding EPDS scores using Pearson’s correlation. Out of 39 women recruited – 27 completed their postpartum visit and provided a paired antenatal – postnatal serum specimen. Serum cytokine evaluations revealed elevations in cytokine concentrations for IL-17A and TNF-α in the pregnancy and postpartum period. IL-6 was elevated in the postpartum period alone. Significant positive correlations were noted between elevated antepartum EPDS scores and IL-6 (r=0.3639; P=0.034), IL-17A (r=0.8682; P< 0.0001), and TNF-α (r=0.7029; P< 0.0001). The same findings were also found between elevated postpartum EPDS scores and IL-6 (r=0.6716; P=0.0001), IL-17A (r=0.8846; P< 0.0001), and TNF-α (r=0.8676; P< 0.0001). Our data demonstrate increases in distinct serum cytokines among women with elevated EPDS scores in both the pregnant and postpartum state. Further studies are warranted to evaluate the influence of immunomodulatory regulators on the neurobehavioral axis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)