Abstract
Purpose: The kynurenine (Kyn) pathway may play a role in the pathophysiology of schizophrenia. This pathway shows crosstalk with proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and/or brain-derived neurotrophic factor (BDNF). Moreover, Kyn metabolites affect neurotransmission and cause neurotoxicity. To date, the influence of the Kyn pathway on proinflammatory cytokines and BDNF remains to be fully elucidated. The aim of this study was to investigate the relationships of the Kyn pathway with proinflammatory cytokines, BDNF, and psychiatric symptoms in patients with schizophrenia.Methods: Thirty patients with schizophrenia and ten healthy control participants were recruited for this study. All patients were diagnosed with schizophrenia using the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5). The healthy controls were those who did not fulfill any of the diagnostic criteria in the DSM-5. The serum levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF were measured in patients with schizophrenia and healthy controls. Patients with schizophrenia were also assessed for psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS).Results: Patients with schizophrenia and healthy controls showed no significant differences in the levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF. A significant positive correlation was found between the serum levels of TNF-α and Kyn (r = 0.53, p = 0.0026) and the Kyn/tryptophan (Trp) value (r = 0.67, p = 0.000046) in the schizophrenia group, but not in the healthy control group.Conclusion: TNF-α affects the Kyn pathway in patients with chronic schizophrenia, but not in the healthy individuals, although serum TNF-α levels showed no difference between the two groups. Associations between the Kyn pathway and the levels of proinflammatory cytokines and BDNF or psychotic symptoms might be complicated in hospitalized patients with chronic schizophrenia.
Highlights
The pathophysiology of schizophrenia is currently unclear, inflammation has been suggested to play an important role in the pathophysiology [1, 2]
The aim of the present study was to investigate the associations of proinflammatory cytokines, including IL-1β, IL6, tumor necrosis factor-α (TNF-α), and IL-10, a suppressive cytokine, and brain-derived neurotrophic factor (BDNF) with the Kyn pathway, which might be related to the symptomatology of schizophrenia patients
We evaluated the serum levels of metabolites of the Kyn pathway (Trp, Kyn, 3-HK, quinolinic acid (QA), 5-HT, Kyn/Trp, 5-HT/Kyn, 3HK/Kyn, QA/Kyn) in patients with schizophrenia and healthy controls
Summary
The pathophysiology of schizophrenia is currently unclear, inflammation has been suggested to play an important role in the pathophysiology [1, 2]. There is growing evidence of an interaction between inflammation and the kynurenine (Kyn) pathway in schizophrenia [3]. The Kyn pathway is regulated by the immune system, and the decomposition of tryptophan via the Kyn pathway is activated by proinflammatory cytokines. The Kyn pathway is considered to crosstalk with the immune system, proinflammatory cytokines, and neurotrophic factors [4, 5]. Tryptophan (Trp) is degraded to Kyn, which is catabolized to either kynurenic acid (KynA) via kynurenine aminotransferases or to 3hydroxykynurenine (3-HK) via kynurenine 3-monooxygenase and to quinolinic acid (QA). Proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), are thought to contribute to the pathogenesis of psychiatric symptoms in schizophrenia by Kyn pathway activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
