Maternal mood disorders are associated with increased proportion of placental immune cell types driving gene expression differences

Maternal mood disorders during pregnancy increase the risk of neurodevelopmental adversities in children. Alterations in placental function may play a role but remain largely unexplored. In the InTraUterine Sampling in Early Pregnancy study, we investigated differential gene expression in first-trimester chorionic villi (n = 267) and birth placentas (n = 493) in relation to maternal history of mood disorder diagnoses, antidepressant and anxiolytic medication purchases derived from medical registers, and depressive and anxiety symptoms reported using the Center for Epidemiologic Studies Depression Scale and Spielberger State Anxiety Inventory during pregnancy. We also estimated differences in relative abundancies of placental cell types and whether these explained potential gene expression differences. Maternal history of mood disorders and depressive and anxiety symptoms above clinical cutoffs, but not medication purchases, were associated (pFDR < 0.1) with overall 285 differentially expressed genes (DEGs) in the placenta. These gene expression changes were moderately correlated with those in chorionic villi, where no significant DEGs were detected. 247 up-regulated DEGs were enriched in immune response and inflammation pathways, and expression in placental immune cells. Moreover, placentas from mothers with a history of mood disorders and symptoms during pregnancy showed higher relative abundances of maternal and fetal immune cell types, which largely explained the observed gene expression differences. Further, expression of up-regulated DEGs correlated positively with inflammatory marker GlycA levels in both maternal mid-pregnancy and fetal cord blood plasma. Our study identifies a placental molecular signature of maternal depression and anxiety during pregnancy offering insights into potential mechanisms linking them with neurodevelopmental adversities in children.