Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia
Abstract 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 st...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-86390-4 |
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| Summary: | Abstract 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. |
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| ISSN: | 2045-2322 |