Kuuskmäe Carolin, Philips Mari-Anne, Kilk Kalle, Haring Liina, Kangro Raul, Seppo Indrek, Zilmer Mihkel, Vasar Eero
Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Estonia.
Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Estonia.
Psychiatry Res. 2023 Oct;328:115423. doi: 10.1016/j.psychres.2023.115423. Epub 2023 Aug 19.
The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients.
本研究的目的是评估精神分裂症谱系障碍（SSD）及长期（5.1年）应用抗精神病药物（AP）治疗如何影响色氨酸（Trp）代谢产物的血清水平。共有112名成年人（54例首发精神病[FEP]患者和58名对照受试者[CSs]）参与了该研究。所研究的代谢产物水平变化出现在患者BMI和腰围持续增加的背景下。关于犬尿氨酸（KYN）途径，在未使用过AP的FEP患者中观察到最强的变化。疾病早期患者血样中的Trp、KYN、犬尿酸（KYNA）和邻氨基苯甲酸（ANT）水平显著降低。此外，这些患者的3-羟基犬尿氨酸（3-HK）和喹啉酸（QUIN）水平略低。KYN途径中的大多数这些变化在AP治疗后变弱。血清素及其代谢产物5-羟吲哚乙酸（5-HIAA）水平在5.1年时，在血清素周转率升高与BMI和腰围增加相关的患者中往往较高。与BMI升高密切相关的黄尿酸（XA）与KYNA的比值也有类似趋势。总之，本研究支持Trp代谢产物在SSD患者肥胖和代谢综合征发生中的作用。
