Genetic variants of the kynurenine-3-monooxygenase and postpartum depressive symptoms after cesarean section in Chinese women

Abstract

Background: New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section.

Methods: A total of 710 Chinese women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥13. Subsequently, 24 women with PDS and 48 matched women without PDS were randomly selected for investigation of perinatal serum concentrations of KYN, 3-HK and the 3-HK/KYN ratio. The 3-HK/KYN ratio indicates the activity of KMO. In addition, 6 single nucleotide polymorphisms of the KMO gene were examined. Following this genotyping, 36 puerperant women carrying the KMO rs1053230 AG genotype and 72 matched puerperant women carrying the KMO rs1053230 GG genotype were selected for comparisons of KYN, 3-HK and 3-HK/KYN ratio levels.

Results: The results show the incidence of PDS in the Chinese population to be 7.3%, with PDS characterized by increased serum 3-HK concentration and 3-HK/KYN ratio, versus matched postpartum women without PDS (P<0.05). Furthermore, polymorphisms of KMO rs1053230 are significantly associated with the incidence of PDS (P<0.05). The serum concentrations of 3-HK and the 3-HK/KYN ratio in postpartum women carrying the KMO rs1053230 AG genotype are significantly higher than those in matched postpartum women carrying the KMO rs1053230 GG genotype.

Conclusions: The presented data highlight the contribution of alterations in the KP to the pathogenesis of postpartum depression. Heightened KMO activity, including as arising from KMO rs1053230 G/A genetic variations, are indicated as one possible mechanism driving the biological underpinnings of PDS.

Keywords: Kynurenine pathway; Kynurenine-3-monooxygenase; Postpartum depressive symptoms; Single nucleotide polymorphism.