Investigation of the Effects of Kynurenine Pathway on Cognitive Functions in Patients with Schizophrenia

OBJECTIVE: The aim of this study is to investigate the effects of the kynurenine pathway on cognitive impairments and clinical symptoms by comparing schizophrenia patients and healthy controls. By doing so, a deeper understanding of the neurobiological foundations of schizophrenia will be gained, and potential therapeutic targets that could improve treatment strategies will be identified. METHODS: The study included 46 schizophrenia patients in remission and 42 healthy controls matched for age, gender, and education level. Participants underwent the Positive and Negative Syndrome Scale (SAPS and SANS). Additionally, a neuropsychological test battery, including the Wisconsin Card Sorting Test (WCST), Stroop Test, Trail Making Test (TMT), and Rey Auditory Verbal Learning Test (R-AVLT), was administered to both groups. Serum levels of serotonin, kynurenic acid (KYNA), indoleamine 2,3-dioxygenase (IDO), high-sensitivity C-reactive protein (hs-CRP), and neopterin were measured in both groups using ELISA kits. RESULTS: The serum levels of KYNA, serotonin, IDO, and neopterin were found to be significantly lower in schizophrenia patients compared to healthy controls. A negative correlation was observed between KYNA levels and interference time in the Stroop Test. A positive correlation was found between serotonin levels and the correct responses in the Rey Auditory Verbal Learning Test (R-AVLT) B1. Additionally, neopterin levels showed a positive correlation with the number of categories completed in the WCST and a negative correlation with the number of trials required to complete the first category. CONCLUSION: The kynurenine pathway and serotonin levels have significant effects on the cognitive functions of schizophrenia patients. Low KYNA levels were strongly associated with cognitive impairments, while higher serotonin levels were found to improve cognitive performance. The relationship between neopterin levels and cognitive flexibility suggests that this biomarker may play an important role in the neuropsychological profile of schizophrenia. These findings indicate that the tryptophan metabolism pathway could be a potential therapeutic target in schizophrenia treatment, suggesting that treatment strategies could be more targeted at the biochemical level.