首发精神病患者血清犬尿酸升高且对抗抑郁药反应不足。

IF 3 Q2 PSYCHIATRY
Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis
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引用次数: 0

摘要

色氨酸代谢犬尿氨酸途径(KP)可被增强的炎症反应激活,并被认为与精神分裂症的病理生理学有关。然而,几乎没有证据表明 KP 在精神疾病的早期病程中失调。我们旨在研究 KP 在首发精神病患者(FEP)中潜在的免疫介导的高活性以及与症状严重程度和治疗反应结果的关系。研究人员对104名抗精神病药物无效的FEP患者和80名健康对照组(HC)进行了血清免疫测定,以测量外周炎症细胞因子(IL-1β、IL-10、TNF-a)、KP限速酶(IDO/TDO)和犬尿酸(KYNA)代谢物的水平。在入院时和接受抗精神病药物治疗 4 周后,采用阳性和阴性综合征量表 (PANSS) 和全球功能评估量表 (GAF) 评估精神病理学和功能状况。与HC相比,FEP患者在抗精神病药物治疗前后的细胞因子和KP成分水平均大幅升高。在FEP患者中观察到促炎性IL-1β和KYNA水平之间存在明显的正相关,而在HC患者中则没有发现。重要的是,患者内部分析表明,基线 KYNA 水平较高的患者会出现更严重的阴性症状,随访时的临床改善程度也较差。这些研究结果表明,KP在早期精神病中上调,可能是通过诱导IL-1β依赖性途径,而外周KYNA升高可能是FEP患者对抗精神病药物无反应的一个有希望的指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics.

Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics.

The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.

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