Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Brain Behav Immun. 2023 Oct;113:1-11. doi: 10.1016/j.bbi.2023.06.016. Epub 2023 Jun 21.
The kynurenine pathway (KP) of tryptophan has been implicated in the pathogenesis of schizophrenia and its interaction with the immune system has been suggested to play a role. In this study, 28 schizophrenia patients and 25 healthy controls were recruited and divided into different inflammatory subgroups using a two-step recursive clustering analysis. Cytokine gene expression and plasma KP metabolites were measured before, during and after treatment. Our findings indicated that schizophrenia patients had lower levels of Tryptophan (TRP), N-formylkynurenine (NFK), xanthinic acid (XA), quinolinic acid (QA), kynurenic acid (KYNA), KYNA/KYN and QA/KYNA, but higher levels of IL-18 mRNA, KYN/TRP compared to healthy controls (all p < 0.05). After electroconvulsive therapy (ECT), patients with low inflammation achieved better clinical improvement (PANSS scores) compared to those with high inflammation (F = 5.672, P = 0.025), especially in negative symptoms (F = 6.382, P = 0.018, η = 0.197). While IL-18 mRNA (F = 32.910, P < 0.0001) was significantly decreased following ECT, the KYN/TRP (F = 3.455, p = 0.047) and KYNA/TRP (F = 4.264, P = 0.026) only significantly decreased in patients with low inflammation. Correlation analyses revealed that baseline IL-18 gene expression significantly correlated with pre- (r = 0.537, p = 0.008) and post-KYNA/TRP (r = 0.443, p = 0.034), post-KYN/TRP (r = 0.510, p = 0.013), and post-negative symptoms (r = 0.525, p = 0.010). Moreover, baseline TRP (r = -0.438, p = 0.037) and XA (r = -0.516, p = 0.012) were negatively correlated with baseline PANSS, while post-KYN (r = -0.475, p = 0.022), 2-AA (r = -0.447, p = 0.032) and KYN/TRP (r = -0.566, p = 0.005) were negatively correlated with Montreal Cognitive Assessment (MoCA) following ECT. Overall, these findings suggested that the association between inflammation and kynurenine pathway plays an essential role in mechanism of ECT for schizophrenia and that the regulation of ECT on KP is influenced by inflammatory characteristics, which may relate to clinical efficacy in schizophrenia.
色氨酸的犬尿酸途径（KP）与精神分裂症的发病机制有关，其与免疫系统的相互作用被认为发挥了作用。在这项研究中，招募了 28 名精神分裂症患者和 25 名健康对照者，并使用两步递归聚类分析将其分为不同的炎症亚组。在治疗前后测量了细胞因子基因表达和血浆 KP 代谢物。我们的研究结果表明，与健康对照组相比，精神分裂症患者的色氨酸（TRP）、N-甲酰犬尿氨酸（NFK）、黄嘌呤酸（XA）、喹啉酸（QA）、犬尿氨酸（KYNA）、KYNA/KYN 和 QA/KYNA 水平较低，但白细胞介素-18 mRNA、KYN/TRP 水平较高（均 P < 0.05）。电抽搐治疗（ECT）后，炎症程度较低的患者与炎症程度较高的患者相比，临床改善（PANSS 评分）更好（F = 5.672，P = 0.025），尤其是在阴性症状方面（F = 6.382，P = 0.018，η = 0.197）。虽然白细胞介素-18 mRNA（F = 32.910，P < 0.0001）在 ECT 后显著降低，但 KYN/TRP（F = 3.455，p = 0.047）和 KYNA/TRP（F = 4.264，P = 0.026）仅在炎症程度较低的患者中显著降低。相关性分析显示，基线白细胞介素-18 基因表达与基线前（r = 0.537，p = 0.008）和基线后 KYNA/TRP（r = 0.443，p = 0.034）、KYN/TRP（r = 0.510，p = 0.013）和基线后阴性症状（r = 0.525，p = 0.010）显著相关。此外，基线 TRP（r = -0.438，p = 0.037）和 XA（r = -0.516，p = 0.012）与基线 PANSS 呈负相关，而基线后 KYN（r = -0.475，p = 0.022）、2-AA（r = -0.447，p = 0.032）和 KYN/TRP（r = -0.566，p = 0.005）与 ECT 后蒙特利尔认知评估（MoCA）呈负相关。总的来说，这些发现表明炎症与犬尿酸途径之间的关联在精神分裂症 ECT 的机制中起着重要作用，ECT 对 KP 的调节受炎症特征的影响，这可能与精神分裂症的临床疗效有关。
