Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory

Carolin Kuuskmäe; Mari-Anne Philips; Kalle Kilk; Liina Haring; Raul Kangro; Indrek Seppo; Mihkel Zilmer; Eero Vasar

doi:10.1016/j.psychres.2023.115423

Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory

Psychiatry Res. 2023 Oct:328:115423. doi: 10.1016/j.psychres.2023.115423. Epub 2023 Aug 19.

Authors

Carolin Kuuskmäe¹, Mari-Anne Philips², Kalle Kilk², Liina Haring³, Raul Kangro⁴, Indrek Seppo⁵, Mihkel Zilmer², Eero Vasar²

Affiliations

¹ Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Estonia. Electronic address: carolin.kuuskmae@ut.ee.
² Institute of Biomedicine and Translational Medicine, Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Estonia.
³ Institute of Clinical Medicine, University of Tartu, Estonia; Psychiatry Clinic of Tartu University Hospital, Estonia.
⁴ Institute of Mathematics and Statistics, University of Tartu, Estonia.
⁵ School of Economics and Business Administration, University of Tartu, Estonia.

PMID: 37639988
DOI: 10.1016/j.psychres.2023.115423

Abstract

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.

Keywords: Body mass index; KAT-II; KMO; KYN; Metabolic syndrome; Trp.