1. The association between inflammation and kynurenine pathway metabolites in electroconvulsive therapy for schizophrenia: Implications for clinical efficacy.
- Author
-
Wang, Yu, Fang, Xinyu, Wang, Guangfa, Tang, Wei, Liu, Shasha, Yang, Yujing, Chen, Jin, Ling, Yuru, Zhou, Chao, Zhang, Xiangrong, Zhang, Caiyi, and Su, Kuan-Pin
- Subjects
- *
ELECTROCONVULSIVE therapy , *KYNURENINE , *QUINOLINIC acid , *MONTREAL Cognitive Assessment , *SCHIZOPHRENIA - Abstract
[Display omitted] • Cytokine gene expression and its interaction with kynurenine pathway play important roles in the pathophysiology and treatment of schizophrenia. • Schizophrenia with high inflammation showed higher cytokine gene expression and KYN/TRP compared to those with low inflammation. • Abnormal cytokine gene expression and plasma KP metabolites were partially normalized after repeated ECT. • Cytokine gene expression significantly correlated with KP during ECT, and was related to clinical efficacy. 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, η2 = 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF