To our best knowledge, no previous study assessed the relationship between plasma concentrations of arginine vasopressin (AVP) and postpartum depression (PPD). Based on our findings, the prevalence of PPD was 9.57% at 6–8 weeks postpartum (the depression confirmed by a psychiatrist). Among the study population, 53.3% were primiparous and 46.7% were multiparous, while among the depressed people, 37.5% were primiparous and 62.5% were multiparous. In the logistic regression, primiparous status was a significant negative predictor of depression. Some studies show that primiparas are more anxious during pregnancy rather than in the postpartum period. Our study also confirms that primiparas are mostly happy with the birth of a newborn and having a new family member, which reduced the EPDS score. In a study by Righetti-Veltema et al (1997) in Geneva on the risk factors and predictive signs of postpartum depression at three months after delivery, multiparas reported more difficult pregnancies and higher anxiety and were less involved in the perinatal preparation program (27). Figueiredo and Conde (2011) reported that parity has a significant impact on postpartum anxiety and depression. According to their study, second-time parents showed more anxiety and depression symptoms than first-time parents in the second and third trimesters and also 3 months after childbirth, but not at birth (28). The results of these two studies were in line with our results. O'Hara et al (1982) reported that pregnant women and primiparous women experienced more depressive symptoms, marital distress, and psychological problems than non-pregnant women (29). In Kaij et al study (1996), symptoms of depression decreased (using the Edinburg postnatal depression scale) with an increasing number of children (30). Gotlib et al (1989) showed that multiparity was a risk factor for depression during pregnancy, but not in the postpartum period (31). Wenzel et al (2005) claimed that there was typically no relationship between parity and depression during pregnancy and postpartum (32), which is consistent with the study of Lashkaripour et al (2012) (33). Four above studies showed that there is no clear and well-established conclusion regarding the relationship between primiparous status and postpartum depression. These conflicting results among studies can be due to different tools used for postpartum depression assessment or different times of evaluation. There are also unclear results about the role of other factors affecting the relationship between parity and postpartum depression, such as parents’ education level, socioeconomic factors, and maternal age. We excluded people who were economically disadvantaged to control this variable.
Sixty women (66.6% of all women) had a sex preference. Of these women, 40% had a baby of the non-desired sex that only 20% of them developed PPD. In general, only 16.6% of all women who developed PPD, had a baby the non-desired sex. The majority of depressed women had not gender preference. According to our finding, depression in two group of whom whether their baby had the same gender as they desired before birth (or not), was less than the group of women who did not have preference about the sex of the baby. Preference for the sex of the baby boy is still common in countries such as India, China and have harmful effects on pregnant women. This gender preference of the baby boy is deeply rooted in cultural issues. In these societies, the girl is considered an economic consumer of the family, because most girls get married and because of paying dowry to them, economically to the family (34, 35). In one study, having a baby of the nondesired sex increased the risk of developing postnatal depression (36). The result of these studies contradict our result (Table 2). However, Dhillon and MacArthur in the opposite direction of these studies, identified maternal gender preference in Asian women in the UK was no association with PPD (37).
Within the total sample at 6–8 weeks postpartum, 82 women breastfed exclusively (91.1%), 8 women did not initiate or ceased exclusive breastfeeding. In our study, exclusive breastfeeding included Labbock and Krasovec’s level 1 and 2 (38). A number of studies have revealed no relationship between breastfeeding and postpartum depression (39). In contrast, a number of researches have showed that breastfeeding may protect against postpartum depression (40, 41). These results are consistent with those from the present study suggesting exclusive breastfeeding may help to reduce mother’s postpartum depression. In our study, women who breastfed at 6–8 weeks postpartum had lower scores when compared to women did not initiate or ceased exclusive breastfeeding.
In this study, the mean plasma concentration of AVP was significantly higher in the depressed group than in the non-depressed group; there was a significant positive correlation between mean plasma concentration of AVP and EPDS score. Worldwide epidemiological studies show that depression occurs in women twice as much as men and peaks during the first years postpartum. They also show that the incidence of all mental illnesses increases in the postpartum period (42). One theory argues that the genes involved in postnatal changes in the brain, if not altered normally, increase the risk of postpartum depression. These genes include a subset of maternal genes that mediate signaling pathways of the vasopressin (42) such as hypocretin receptors. Neuromedin S (Nms) also affects this signaling, acting as a mediator in the activity of enkephalin and dynorphin, and plays a key role in the action balance of different neuropeptides (43). No studies have yet examined the relationship between vasopressin serum level and postpartum depression.
Previous studies on non-pregnant populations are as follows. In a 2006 review article, Keck concluded that a dysfunction in the vasopressin (AVP) and corticotropin-releasing factor (CRF) systems is involved in the pathogenesis and etiology of depression and anxiety (44). In chronic stress, vasopressin is steadily elevated in CRH neurons, so that even a slight irritation may lead to a severe AVP/CRH secretion. This can contribute to the development of dysphoric symptoms and may even be a factor responsible for the onset of major or temperament depression (45). The number of CRH neurons, expressing the vasopressin level, increases in depressed human PVN (46). Elevated AVP mRNA level in the SON in depressed individuals (47) also leads to an increase in plasma vasopressin (24), which is related to suicide risk (48), and altered attention and arousal in memory processes in depressed patients (49). In contrast, Wang et al (2008) found no difference in vasopressin mRNA expression in the SON or PVN of depressed individuals compared to the control group, which may be due to the mere presence of melancholic depressed individuals in this study (50). Brunner et al (2002) found no association between vasopressin concentration in plasma and cerebrospinal fluid (CSF) among depressed and non-depressed individuals. The two were also not different in those who attempted suicide compared to other people. This study is not in line with the results of our study. It might be due to a low sample size and diagnostic heterogeneity in the patient and control groups, which did not allow them to investigate the pathogenetic role of vasopressin (51).
Griebel et al (2003) stated that although CRF has been recognized as a key regulator of the stress system, there is evidence that the vasopressinergic system may play an equal role in regulating stress responses, so vasopressin V (1b) receptor antagonists may be potential treatments for depression. Their results confirmed the efficacy of using SSR149415, which was the first selective, orally active vasopressin V (1b) receptor antagonist in the treatment of depression and anxiety disorders caused by traumatic events (52). Vasopressin V (1b) receptor is required for normal response of the cerebellum and adrenal during chronic stress (53). Muller et al (2000) study on mice showed a selective compensatory activation of the hypothalamic vasopressinergic for maintaining basal ACTH secretion and HPA system activity in heterozygous and homozygous Crhr1 mutants (Crhr1−/−) in basal and stress conditions. Deficiency of CRH receptor 1 (CRHR1) severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system and reduces stress-related behavior in mice (54)
In this study, all subjects were controlled as much as possible for the involvement of other factors affecting plasma vasopressin concentration. The results of this study support the role of vasopressin in the pathogenesis of postpartum depression. Since postpartum depression is classified as a sub-type of major depressive disorder, we also support the possible role of vasopressin in major depression. For the first time in the world, we examined the relationship between plasma concentrations of arginine vasopressin (AVP) and the EPDS Score at 6 to 8 weeks postpartum, revealing a significant positive relationship between plasma concentrations of AVP and the EPDS Score.
Study Limitations
This study provides useful data of the relationship between plasma vasopressin and postpartum depression. However, the present study has some limitations. First, we know that it would be better to evaluate levels of plasma concentrations of vasopressin by Radioimmunoassay (RIA) because no study had not used the enzyme-linked immunosorbent assay (ELISA kit) to measure vasopressin. Therefore, more studies are suggested in order to support our results. However, we could not do it because of lack of access to Human Vasopressin Radioimmunoassay (RIA) kits in Iran, which is a limitation of our study.