Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• The tryptophan (TRP)-kynurenine (KYN) pathway is implicated in schizophrenia pathogenesis.
• Investigating TRP-KYN metabolite levels in first-episode schizophrenia (FES) is crucial for understanding disease mechanisms.

Purpose of the Study:

• To examine TRP-KYN metabolite levels in serum and urine of drug-naive FES patients.
• To correlate these metabolite levels with clinical symptoms assessed by the Positive and Negative Syndrome Scale (PANSS).

Main Methods:

• Included 38 drug-naive FES patients and 43 healthy controls (HCs).
• Quantified TRP-KYN metabolites in serum and urine.
• Assessed clinical symptoms using PANSS.

Main Results:

• FES patients had higher serum quinolinic acid/kynurenic acid (QUIN/KYNA) ratio and urine KYN/TRP ratio compared to HCs.
• Reduced serum kynurenic acid (KYNA), xanthurenic acid (XA), and urine picolinic acid (PIC) were observed in FES patients.
• A decreased urine PIC/QUIN ratio and a negative correlation between urine KYNA/KYN ratio and PANSS scores were found.

Conclusions:

• FES patients exhibit peripheral TRP-KYN pathway dysregulation.
• Increased neurotoxic metabolites (e.g., QUIN/KYNA ratio) and reduced neuroprotective metabolites suggest a role in schizophrenia pathophysiology.
• This pathway dysregulation, favoring neurotoxic product generation, may contribute to schizophrenia development.