Nilsson-Todd Linda K, Nordin Conny, Jönsson Erik G, Skogh Elisabeth, Erhardt Sophie
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
2Department of Neuroscience and Locomotion, Psychiatry Section, Linköpings Universitet, Linköping, Sweden.
Acta Neuropsychiatr. 2007 Feb;19(1):45-52. doi: 10.1111/j.1601-5215.2006.00170.x.
The tryptophan metabolite kynurenic acid (KYNA) is an endogenous glutamate/nicotinic receptor antagonist. Previous studies have shown that the concentration of the compound is increased in cerebrospinal fluid (CSF) of patients with schizophrenia. Furthermore, it has been found that the CSF concentration of KYNA is positively correlated to CSF concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) in healthy control subjects.
To study the correlations between KYNA and the monoamine metabolites HVA, 5-HIAA and 4-hydroxy-3-methoxyphenylglycol (HMPG) in CSF of male patients (n= 53, ranging from 20 to 48 years of age) with verified schizophrenia.
CSF was obtained by lumbar puncture, and KYNA analysis was performed with an isocratic reversed-phase high-performance liquid chromatography system connected to a fluorescence detector. HVA, 5-HIAA and HMPG concentrations were measured by mass fragmentography with deuterium-labelled internal standards.
Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA, while CSF content of HMPG did not correlate to KYNA or any of the monoamine metabolites in CSF.
The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia.
色氨酸代谢产物犬尿喹啉酸(KYNA)是一种内源性谷氨酸/烟碱受体拮抗剂。先前的研究表明,精神分裂症患者脑脊液(CSF)中该化合物的浓度会升高。此外,还发现健康对照者中,CSF中KYNA的浓度与单胺代谢产物高香草酸(HVA)和5-羟吲哚乙酸(5-HIAA)的CSF浓度呈正相关。
研究确诊为精神分裂症的男性患者(n = 53,年龄20至48岁)CSF中KYNA与单胺代谢产物HVA、5-HIAA和4-羟基-3-甲氧基苯乙二醇(HMPG)之间的相关性。
通过腰椎穿刺获取CSF,使用连接荧光检测器的等度反相高效液相色谱系统进行KYNA分析。采用带有氘标记内标的质谱碎片分析法测量HVA、5-HIAA和HMPG的浓度。
CSF中KYNA、HVA和5-HIAA之间存在正相关,而CSF中HMPG的含量与KYNA或CSF中的任何单胺代谢产物均无相关性。
本研究结果表明,KYNA生成增加与男性精神分裂症患者多巴胺和5-羟色胺周转率增加有关。