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Prepartum depression is associated with early adversity, pregnancy complications, preterm delivery, postpartum depression, and long-term effects on child neurodevelopment. The oxytocin (OXT) system is affected by early adverse experiences and has been associated with depression. In the current study, we investigated risk factors for prenatal depressive symptoms, mainly the effects of early childhood and adolescence trauma, in combination with the presence of certain variants of polymorphisms of OXT and OXT receptor (OXTR) genes. We hypothesized that early childhood and adolescence trauma has higher negative effects in carriers of genetic variants of the OXT/OXTR system, increasing their risk for depression. Early in pregnancy (8-14 weeks), 141 pregnant women from a Uruguayan population were asked to provide DNA samples and complete questionnaires that assessed their experience of child abuse, depression symptoms, and other variables that included demographic information. Our results showed that 23.5% of pregnant women had depressive symptoms. Several OXT and OXTR genetic variants were associated with higher risk of prepartum depression only in those pregnant women who suffered emotional abuse during infancy or adolescence. Logistic regression (Nagelkerke's R 2  = .33) revealed that women who suffered early abuse and were carriers of the variants CC of rs2740210 (OXT) or AA of rs237887 (OXTR) had significantly higher risk of experiencing depressive symptoms. Antecedents of psychiatric disorders also contributed to the risk of depression. We conclude that emotional abuse contributes to the risk of depression in different ways in women carrying different OXT and OXTR genetic variants. Early detection and closer follow-up of women with child abuse and certain OXT genetic variants, among other risk factors, could reduce the long-term impact of prepartum depression., (© 2023 Wiley Periodicals LLC.)