C-Reactive protein and the kynurenic acid to quinolinic acid ratio are independently associated with white matter integrity in major depressive disorder.
C-Reactive protein and the kynurenic acid to quinolinic acid ratio are independently associated with white matter integrity in major depressive disorder.
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C反应蛋白和犬尿酸与喹啉酸的比例与重度抑郁症的白质完整性独立相关。
DOI：
10.1016/j.bbi.2022.07.011
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发表时间：
2022-10
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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犬尿酸（KynA）和喹啉酸（QA）是具有神经活性的犬尿氨酸途径（KP）代谢物，分别具有神经保护和神经毒性。至少部分由于免疫激活，重度抑郁症（MDD）患者血液中KynA与QA的比例降低，并且据报道与抑郁症患者的灰质体积呈正相关。本研究考察了炎症介质c -反应蛋白（CRP）和假定的神经保护指数KynA/QA是否与MDD的白质完整性相关，其次，这些关联是否相互独立，或者CRP的作用是否由KynA/QA介导。在Tulsa 1000研究中，有166名诊断为DSM-V的MDD参与者完成了弥散张量成像，并提供了用于定量CRP、KynA和QA的血清样本。使用DSI Studio进行相关神经束造影，绘制与CRP和KynA/QA相关的特定白质通路。在控制了年龄、性别、体重指数（BMI）、用药状况、终生酒精使用、抑郁严重程度、焦虑严重程度、病程、吸烟状况等9个可能的混杂因素后，CRP与KynA/QA呈负相关（标准化β系数，SBC= - 0.35，标准误差，Std.E=0.13, p < 0.01）。在控制了9个潜在的混杂因素（SBC= - 0.43, Std.E=0.13, p = 0.002）后，较高的CRP浓度与双侧扣带和穹窿白质完整性（分数各向异性，FA）降低相关。在控制了相同可能的混杂因素后，较高的血清KynA/QA与双侧穹窿、双侧丘脑上辐射、胼胝体和双侧扣带束白质完整性的增加有关（SBC= 0.26，标准差=0.09,p = 0.005）。CRP与FA之间的关系不是由KynA/QA介导的。探索性分析还显示，KynA/QA与PANASX测量的自我报告的积极情绪、注意力和疲劳相关，而CRP无关（sbc = 0.17-0.23）。综上所述，这些结果与假设一致，即在MDD患者亚组中，较高水平的全身性炎症改变了KP代谢的平衡，但也提高了CRP和神经活性KP代谢物代表MDD白质改变的独立分子机制的可能性。
Kynurenic acid (KynA) and quinolinic acid (QA) are neuroactive kynurenine pathway (KP) metabolites that have neuroprotective and neurotoxic properties, respectively. At least partly as a result of immune activation, the ratio of KynA to QA in the blood is reduced in major depressive disorder (MDD) and has been reported to be positively correlated with gray matter volume in depression. This study examined whether the inflammatory mediator, C-reactive protein (CRP) and the putative neuroprotective index, KynA/QA, were associated with white matter integrity in MDD, and secondly, whether any such associations were independent of each other or whether the effect of CRP was mediated by KynA/QA. One hundred and sixty-six participants in the Tulsa 1000 study with a DSM-V diagnosis of MDD completed diffusion tensor imaging and provided a serum sample for the quantification of CRP, KynA, and QA. Correlational tractography was performed using DSI Studio to map the specific white matter pathways that correlated with CRP and KynA/QA. CRP was negatively related to KynA/QA (standardized beta coefficient, SBC=−0.35 with standard error, Std.E=0.13, p < 0.01) after controlling for nine possible confounders, i.e., age, sex, body mass index (BMI), medication status, lifetime alcohol use, severity of depression, severity of anxiety, length of illness, and smoking status . Higher concentrations of CRP were associated with decreased white matter integrity (fractional anisotropy, FA) of the bilateral cingulum and fornix after controlling for the nine potential confounders (SBC= −0.43, Std.E=0.13, p = 0.002). Greater serum KynA/QA was associated with increased white matter integrity of the bilateral fornix, bilateral superior thalamic radiations, corpus callosum, and bilateral cingulum bundles after controlling for the same possible confounders (SBC= 0.26, Std.E=0.09, p = 0.005). The relationship between CRP and FA was not mediated by KynA/QA. Exploratory analyses also showed that KynA/QA but not CRP was associated with self-reported positive affect, attentiveness, and fatigue measured with the PANASX (SBCs = 0.17-0.23). Taken together, these results are consistent with the hypothesis that within a subgroup of MDD patients, a higher level of systemic inflammation alters the balance of KP metabolism but also raise the possibility that CRP and neuroactive KP metabolites represent independent molecular mechanisms underlying white matter alterations in MDD.
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影响因子：
11
作者：
Felger JC;Haroon E;Patel TA;Goldsmith DR;Wommack EC;Woolwine BJ;Le NA;Feinberg R;Tansey MG;Miller AH
通讯作者：
Miller AH
影响因子：
5.7
作者：
Bastiani M;Cottaar M;Fitzgibbon SP;Suri S;Alfaro-Almagro F;Sotiropoulos SN;Jbabdi S;Andersson JLR
通讯作者：
Andersson JLR
影响因子：
11
作者：
Georgin-Lavialle, S.;Moura, D. S.;Gaillard, R.
通讯作者：
Gaillard, R.
影响因子：
6.6
作者：
DeWitt, Samuel J.;Bradley, Kailyn A.;Gabbay, Vilma
通讯作者：
Gabbay, Vilma
影响因子：
2.5
作者：
FOSTER, AC;VEZZANI, A;SCHWARCZ, R
通讯作者：
SCHWARCZ, R