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Abstract：
BACKGROUND: Perinatal depression (including antenatal-, postnatal-, and depression that spans both timepoints) is a prevalent disorder with high morbidity that affects both mother and child. Even though the full biological blueprints of perinatal depression remain incomplete, multiple studies indicate that, at least for antenatal depression, the disorder has an inflammatory component likely linked to a dysregulation of the enzymatic kynurenine pathway. The production of neuroactive metabolites in this pathway, including quinolinic acid (QUIN), is upregulated in the placenta due to the multiple immunological roles of the metabolites during pregnancy. Since neuroactive metabolites produced by the pathway also may affect mood by directly affecting glutamate neurotransmission, we sought to investigate whether the placental expression of kynurenine pathway enzymes controlling QUIN production was associated with both peripheral inflammation and depressive symptoms during pregnancy.
METHODS: 68 placentas obtained at birth were analyzed using qPCR to determine the expression of kynurenine pathway enzymes. Cytokines and metabolites were quantified in plasma using high-sensitivity electroluminescence and ultra-performance liquid chromatography, respectively. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) throughout pregnancy and the post-partum. Associations between these factors were assessed using robust linear regression with ranked enzymes.
RESULTS: Low placental quinolinate phosphoribosyl transferase (QPRT), the enzyme responsible for degrading QUIN, was associated with higher IL-6 and higher QUIN/kynurenic acid ratios at the 3rd trimester. Moreover, women with severe depressive symptoms in the 3rd trimester had significantly lower placental expression of both QPRT and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD); impaired activity of these two enzymes leads to QUIN accumulation.
CONCLUSIONS: Overall, our data support that a compromised placental environment, featuring low expression of critical kynurenine pathway enzymes is associated with increased levels of plasma cytokines and the dysregulated kynurenine metabolite pattern observed in depressed women during pregnancy.
METHODS: 68 placentas obtained at birth were analyzed using qPCR to determine the expression of kynurenine pathway enzymes. Cytokines and metabolites were quantified in plasma using high-sensitivity electroluminescence and ultra-performance liquid chromatography, respectively. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) throughout pregnancy and the post-partum. Associations between these factors were assessed using robust linear regression with ranked enzymes.
RESULTS: Low placental quinolinate phosphoribosyl transferase (QPRT), the enzyme responsible for degrading QUIN, was associated with higher IL-6 and higher QUIN/kynurenic acid ratios at the 3rd trimester. Moreover, women with severe depressive symptoms in the 3rd trimester had significantly lower placental expression of both QPRT and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD); impaired activity of these two enzymes leads to QUIN accumulation.
CONCLUSIONS: Overall, our data support that a compromised placental environment, featuring low expression of critical kynurenine pathway enzymes is associated with increased levels of plasma cytokines and the dysregulated kynurenine metabolite pattern observed in depressed women during pregnancy.
摘要：
背景：围产期抑郁症（包括产前-，Postnatal-,和跨越两个时间点的抑郁症）是一种流行的疾病，发病率高，影响母亲和孩子。即使围产期抑郁症的完整生物学蓝图仍然不完整，多项研究表明，至少对于产前抑郁症,该疾病具有炎症成分，可能与酶促犬尿氨酸途径的失调有关。在这个通路中产生神经活性代谢物，包括喹啉酸（QUIN），由于怀孕期间代谢物的多种免疫学作用，在胎盘中上调。由于该途径产生的神经活性代谢物也可能通过直接影响谷氨酸神经传递来影响情绪，我们试图调查控制QUIN产生的犬尿氨酸途径酶的胎盘表达是否与妊娠期间的外周炎症和抑郁症状相关.
方法：使用qPCR分析出生时获得的68个胎盘，以确定犬尿氨酸途径酶的表达。使用高灵敏度电致发光和超高效液相色谱法定量血浆中的细胞因子和代谢物，分别。在整个怀孕和产后期间，使用爱丁堡产后抑郁量表（EPDS）评估产妇的抑郁症状。使用具有排序酶的稳健线性回归评估这些因素之间的关联。
结果：胎盘喹啉酸磷酸核糖转移酶（QPRT）低，负责降解QUIN的酶，在妊娠晚期与更高的IL-6和更高的QUIN/犬尿烯酸比率相关。此外，妊娠晚期有严重抑郁症状的女性,QPRT和2-氨基-3-羧基羧酸-6-半醛脱羧酶(ACMSD)的胎盘表达均显著降低;这两种酶活性受损导致QUIN积累.
结论：总体而言，我们的数据支持胎盘环境受损，关键犬尿氨酸途径酶的低表达与妊娠期间抑郁妇女中观察到的血浆细胞因子水平升高和犬尿氨酸代谢异常模式相关。
方法：使用qPCR分析出生时获得的68个胎盘，以确定犬尿氨酸途径酶的表达。使用高灵敏度电致发光和超高效液相色谱法定量血浆中的细胞因子和代谢物，分别。在整个怀孕和产后期间，使用爱丁堡产后抑郁量表（EPDS）评估产妇的抑郁症状。使用具有排序酶的稳健线性回归评估这些因素之间的关联。
结果：胎盘喹啉酸磷酸核糖转移酶（QPRT）低，负责降解QUIN的酶，在妊娠晚期与更高的IL-6和更高的QUIN/犬尿烯酸比率相关。此外，妊娠晚期有严重抑郁症状的女性,QPRT和2-氨基-3-羧基羧酸-6-半醛脱羧酶(ACMSD)的胎盘表达均显著降低;这两种酶活性受损导致QUIN积累.
结论：总体而言，我们的数据支持胎盘环境受损，关键犬尿氨酸途径酶的低表达与妊娠期间抑郁妇女中观察到的血浆细胞因子水平升高和犬尿氨酸代谢异常模式相关。
