Tryptophan-Kynurenine Pathway Metabolism in the Pathophysiology of Cognitive Impairment in Schizophrenia.

This single-center, prospective study will recruit 100 treatment-naïve, first-episode schizophrenia (SZ) patients at Tianjin Anding Hospital for an 8-week follow-up. All patients will receive monotherapy with risperidone and undergo baseline and week 8 assessments including clinical rating scales and the MATRICS Consensus Cognitive Battery (MCCB), along with peripheral blood sample collection. Concurrently, 100 age-, sex-, and education-matched healthy controls (HCs) will be recruited. Prior data from 300 medication-naïve SZ patients and 100 HCs will be selectively included in the final analysis (totaling 300 SZ patients and 200 HCs). We hypothesize that dysregulation of the tryptophan-kynurenine (TRP-KYN) pathway in SZ patients, leading to an imbalanced ratio of neuroprotective kynurenic acid (KYNA) to neurotoxic quinolinic acid (QUIN), affects inflammatory markers and NMDA receptor (NMDAR) levels, ultimately causing cognitive impairment. Specifically, we will analyze the association between cognitive function and plasma TRP-KYN pathway metabolites in medication-naïve FES patients; relationship between cognitive function and TRP-KYN pathway gene polymorphisms and mRNA expression in medication-naïve FES patients; and changes in cognitive function post-8-week treatment with plasma TRP-KYN pathway mRNA expression and metabolite levels.