The role of kynurenine pathway and kynurenic aminotransferase alleles in postpartum depression following cesarean section in Chinese women

Chengxuan Quan,Na Hu,Kaiming Duan,Guang Zeng,Jiahui Ma,Ge Long,Mi Yang,Saiying Wang,Zhendong Huang,Heya Yu

doi:10.1002/brb3.1566

Abstract

ObjectivesA growing body of data indicates that the kynurenine pathway may play a role in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenic aminotransferase (KAT) is an important kynurenine pathway enzyme, catalyzing kynurenine (KYN) into kynurenic acid (KYNA). This study investigated as to whether genetic variations in KAT are associated with PDS.MethodsA cohort of 360 Chinese women scheduled to undergo cesarean delivery was enrolled into this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13. A total of eight KAT single nucleotide polymorphisms (SNPs) were genotyped and their association with PDS investigated. Serum concentrations of KYN, KYNA, and quinolinic acid (QUIN) in women with or without PDS were also measured. This allowed the determination of the KYNA/KYN ratio, which is reflective of KAT activity.ResultsPostpartum depressive symptoms incidence was 7.2%. Advanced maternal age, lower education, antenatal depression, and postpartum blues were risk factors for PDS (p < .05). Women with PDS, versus non‐PDS, had heightened KYN levels one day prior to surgery (ante‐d1) (p < .05), as well as having significantly lower KYNA and higher QUIN levels at postnatal day three (post‐d3) (p < .05). Women with, versus without, PDS also had a significantly higher QUIN/KYNA ratio at post‐d3 (p < .05). KAT activity was significantly lower in women with, versus without, PDS at ante‐d3 (p < .05). No significant association was evident between the KAT SNPs and PDS.ConclusionOur data support a role for alterations in the kynurenine pathway in the pathogenesis of PDS, although no significant association was found for the eight tested KAT SNPs with PDS.

Highlights

Postpartum depressive symptomatology (PDS) is a depressive syndrome that affects 6.5%–19% of women following childbirth and is the most common mental health disorder following delivery (O'Hara & McCabe, 2013; Stewart & Vigod, 2016)
KYN may be converted to kynurenic acid (KYNA) by kynurenine aminotransferase (KAT) and to 3-hydroxykynurenine (3-HK) by kynurenine-3-monooxygenase (KMO). 3-HK can be converted to further kynurenine pathway products, eventually leading to quinolinic acid (QUIN), which can be excitotoxic via the N-methyl-d-aspartate (NMDA) receptor
The results of the current study showed: (a) Advanced maternal age, lower education, antenatal depression, postpartum blues (PB), and inflammation were PDS risk factors; (b) antenatal depression and PB were the main PDS predictors; (c) the metabolites of kynurenine pathway changed over the perinatal period, and these changes were closely related to the emergence of PDS; (d) KAT activity in women with PDS was lower than that in women without PDS; (e) there was no significant relationship between KAT genetic variations and PDS

Summary

Introduction

Postpartum depressive symptomatology (PDS) is a depressive syndrome that affects 6.5%–19% of women following childbirth and is the most common mental health disorder following delivery (O'Hara & McCabe, 2013; Stewart & Vigod, 2016). Kynurenine pathway was involved in many psychological diseases. TRP is converted to kynurenine (KYN) by indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO). KYN may be converted to kynurenic acid (KYNA) by kynurenine aminotransferase (KAT) and to 3-hydroxykynurenine (3-HK) by kynurenine-3-monooxygenase (KMO). 3-HK can be converted to further kynurenine pathway products, eventually leading to quinolinic acid (QUIN), which can be excitotoxic via the N-methyl-d-aspartate (NMDA) receptor. Heightened QUIN production and NMDA receptor overactivation may be involved in the pathogenesis of depression. KYNA is an endogenous NMDA receptor antagonist, thereby acting to antagonize the excitotoxic effects of QUIN (Duan et al, 2018; Lau & Zukin, 2007; Schwarcz, Bruno, Muchowski, & Wu, 2012)

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