Association of the rs53576 and rs2254298 polymorphisms of the oxytocin receptor gene with gestational and postpartum depression

Abstract

The birth of a child presents a series of challenges and difficulties on the mother, such as stress, reduced hours of sleep, adjustment of the marital relationship and social isolation. Since this is a time marked by biological, psychological and social changes, the gravid-puerperal period is considered to be one of the periods more vulnerable to the occurrence of psychiatric disorders. Among them, major depressive disorder is the one involving the greatest morbidity and is the most frequently occurring psychiatric condition among women of childbearing age. The etiology of depression can still be considered difficult to understand, but we currently recognize that it is multifactorial. Among the possible causes, hypotheses have been raised about biological markers (especially those related to the high levels of inflammatory cytokines), the environment factors (as the occurrence of traumas and of stressful events) and genetic vulnerability, associated mainly to specific genes. This approach assumes that genes, although they are not the single determinants, may play a fundamental role in the establishment of parental behaviors, determining and/or modulating how the environment acts on this attitude pattern. Among the genes more frequently associated to depressive symptoms are those related to the maternal oxytocin receptor gene (OXTR) with its rs 53576 and rs2254298 polymorphisms. In this context, the objective of this study is 1) to investigate the possible association of the maternal oxytocin receptor gene, specifically its rs53576 and rs2254298 polymorphisms, with depressive symptoms during pregnancy and the postpartum period in a sample of Ribeirão Preto (SP) and São Luís (MA) mothers and 2) to investigate the interactions between depressive symptoms and sociodemographic factors (age, socioeconomic status, marital status, schooling, occupation), maternal psychosocial conditions (anxiety, stress, social support, experiences of violence during pregnancy and mother-infant relationship) and biological markers, specifically inflammatory levels of cytokines. The present project has a longitudinal design, with information (mother and/or child) having been obtained at four different times: a) prenatal care, where information was collected about sociodemographic data, depression symptoms, anxiety, stress, social support, experience of violence, in addition to venous blood collection for genetic purposes and cytokine measurements. At this stage, 1377 mothers in Ribeirão Preto and 1445 mothers in São Luís were assessed; b) birth, where information about the birth conditions of the infant and of delivery was obtained for a total of 1348 mothers in Ribeirão Preto and 1380 in São Luís; c) postpartum, where the occurrence of depressive symptoms during this period was assessed for 1059 mothers in Ribeirão Preto and 801 in São Luís and d) second year of life of the babies, which were investigated stress, depression, psychiatric symptoms and the mother-infant relationship for 1077 mothers in Ribeirão Preto and 1138 in São Luís. Univariate and multivariable logistic regression analyses will be used to estimate the associations between the depressive symptoms and genetic, environmental factors and biological markers, including levels of cytokines inflammation, with a 95% confidence interval. The structural equations model will be also used for the analysis of genetic-environmental interactions. Finally, we consider that the recognition of a possible gestational and postpartum depression is important because these conditions may have long-term effects on the child and family. Although deficits are not universal in depressed mothers, depression can lead to reduced interaction and irritability wrongly directed at the children. Without proper treatment, there are high risks of child abuse and neglect, long-term impairment of the mother-child relationship, and psychiatric or learning disorders in the children.