Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia

The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This study included 38 drug-naive patients with FES and 43 healthy controls (HCs). Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Levels of TRP-KYN metabolites in serum and urine were quantified. Patients with FES showed significantly higher serum quinolinic acid/kynurenic acid (QUIN/KYNA) ratio and urine KYN/TRP ratio compared to HCs, while neuroprotective metabolites, including serum KYNA, xanthurenic acid (XA), and urine picolinic acid (PIC) levels, were significantly reduced, along with a decreased urine PIC/QUIN ratio (p < 0.05). The urine KYNA/KYN ratio was negatively correlated with PANSS general psychopathology scores (r = -0.35, p = 0.04) and with PANSS total scores (r = -0.35, p = 0.046). Patients with FES exhibited dysregulation of the peripheral TRP-KYN pathway, characterized by an increased neurotoxic-to-neuroprotective QUIN/KYNA ratio and reduced levels of neuroprotective metabolites. This shift towards increased neurotoxic product generation suggests that the dysregulation of the TRP-KYN pathway could play a role in the pathophysiology of schizophrenia.