Department of Physiology and Pharmacology, Nanna Svartz väg 2, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Schizophr Bull. 2012 May;38(3):426-32. doi: 10.1093/schbul/sbq086. Epub 2010 Aug 20.
The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients. KYNA is an endogenous metabolite of tryptophan (TRP) produced in astrocytes and antagonizes N-methyl-D-aspartate and α7* nicotinic receptors.
The formation of KYNA is determined by the availability of substrate, and hence, we analyzed KYNA and its precursors, kynurenine (KYN) and TRP, in the cerebrospinal fluid (CSF) of patients with schizophrenia. CSF from male patients with schizophrenia on olanzapine treatment (n = 16) was compared with healthy male volunteers (n = 29).
KYN and KYNA concentrations were higher in patients with schizophrenia (60.7 ± 4.37 nM and 2.03 ± 0.23 nM, respectively) compared with healthy volunteers (28.6 ± 1.44 nM and 1.36 ± 0.08 nM, respectively), whereas TRP did not differ between the groups. In all subjects, KYN positively correlated to KYNA.
Our results demonstrate increased levels of CSF KYN and KYNA in patients with schizophrenia and further support the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.
精神分裂症的犬尿酸（KYNA）假说部分基于研究表明患者大脑中的 KYNA 水平升高。KYNA 是色氨酸（TRP）的内源性代谢物，在星形胶质细胞中产生，并拮抗 N-甲基-D-天冬氨酸和 α7*烟碱型受体。
KYNA 的形成取决于底物的可用性，因此，我们分析了精神分裂症患者脑脊液（CSF）中的 KYNA 及其前体犬尿氨酸（KYN）和 TRP。我们比较了接受奥氮平治疗的男性精神分裂症患者（n = 16）和健康男性志愿者（n = 29）的 CSF。
与健康志愿者（分别为 28.6 ± 1.44 nM 和 1.36 ± 0.08 nM）相比，精神分裂症患者的 KYN 和 KYNA 浓度更高（分别为 60.7 ± 4.37 nM 和 2.03 ± 0.23 nM），而 TRP 两组之间无差异。在所有受试者中，KYN 与 KYNA 呈正相关。
我们的研究结果表明，精神分裂症患者的 CSF KYN 和 KYNA 水平升高，进一步支持 KYNA 参与精神分裂症病理生理学的假说。
