Wang Sai-Ying, Duan Kai-Ming, Tan Xiao-Fang, Yin Ji-Ye, Mao Xiao-Yuan, Zheng Wei, Wang Chun-Yan, Yang Mi, Peng Cheng, Zhou Hong-Hao, Liu Zhao-Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China; Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
J Affect Disord. 2017 Jun;215:94-101. doi: 10.1016/j.jad.2017.03.023. Epub 2017 Mar 10.
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.
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.
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.
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.
抑郁症的新概念强调了犬尿氨酸途径（KP）在产后抑郁症状（PDS）发病机制中的作用。犬尿氨酸3-单加氧酶（KMO）是KP的限速酶，它催化犬尿氨酸（KYN）转化为3-羟基犬尿氨酸（3-HK）。先前的研究表明，KMO与抑郁症的病理生理学密切相关。本研究的目的是调查KMO基因的变异是否会影响剖宫产术后PDS的发生。
本研究共纳入710名接受剖宫产的中国女性。通过爱丁堡产后抑郁量表（EPDS）评分≥13来确定PDS。随后，随机选择24名患有PDS的女性和48名匹配的未患PDS的女性，调查围产期血清中KYN、3-HK的浓度以及3-HK/KYN比值。3-HK/KYN比值表示KMO的活性。此外，检测了KMO基因的6个单核苷酸多态性。在进行基因分型后，选择36名携带KMO rs1053230 AG基因型的产妇和72名匹配的携带KMO rs1053230 GG基因型的产妇，比较KYN、3-HK和3-HK/KYN比值水平。
结果显示，中国人群中PDS的发生率为7.3%，与匹配的未患PDS的产后女性相比，PDS的特征是血清3-HK浓度和3-HK/KYN比值升高（P<0.05）。此外，KMO rs1053230的多态性与PDS的发生率显著相关（P<0.05）。携带KMO rs1053230 AG基因型的产后女性血清中3-HK浓度和3-HK/KYN比值显著高于匹配的携带KMO rs1053230 GG基因型的产后女性。
所呈现的数据突出了KP改变对产后抑郁症发病机制的影响。KMO活性增强，包括由KMO rs1053230 G/A基因变异引起的活性增强，被认为是驱动PDS生物学基础的一种可能机制。
