The interaction between estradiol change and the serotonin transporter gene (5-HTTLPR) polymorphism is associated with postpartum depressive symptoms.

Although estrogenic fluctuation is considered a major risk factor for postpartum depression (PPD), the effects of the interactions between the genetic background and estradiol (E2) change on PPD are not well understood. Here, a cohort study with 437 postpartum women was carried out to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and E2 change on the risk of PPD symptoms. The participants were assessed using the Edinburgh Postnatal Depression Scale and the Self-Rating Depression Scale at 1 and 6 weeks after delivery. The PCR-based restriction fragment length polymorphism method was utilized to examine the genotype distribution of the 5-HTTLPR polymorphism, and the serum levels of E2 were determined in individuals in the third trimester of pregnancy and at 1 week postpartum. A significant association was observed between E2 change and PPD susceptibility in the late postpartum period (6 weeks) [P = 0.002, odds ratio (OR) = 2.341, 95% confidence interval (CI) = 1.361-4.027], but it was not observed in the early postpartum period (1 week). There was no significant association between the 5-HTTLPR genotype and PPD risk at both the early and late postpartum periods (P > 0.05). However, the interaction between E2 change and the 5-HTTLPR polymorphism could reasonably influence PPD risk. The women who carried the SS genotype with large decreases in E2 showed a significantly higher risk for PPD at both the early (P = 0.002, OR = 2.525, 95% CI = 1.384-4.059) and late postpartum periods (P < 0.001, OR = 3.108, 95% CI = 1.562-4.436) compared with those who carried the SL/LL genotype. This study suggests that there is an association between E2 change in the perinatal period with the 5-HTTLPR genotype and the occurrence of PPD.