Associations Between the Kynurenine Pathway, Proinflammatory Cytokines, and Brain-Derived Neurotrophic Factor in Hospitalized Patients With Chronic Schizophrenia: A Preliminary Study

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.

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

“…We found a positive correlation between TNF-α and three metabolites: 3-HK, KYN, and QUIN. TNF-α affects the kynurenine pathway in patients with schizophrenia, as a positive correlation between the levels of TNF-α and KYN has been reported (35). TNF-α may accelerate the formation of KYN from the catabolism of TRP (35).…”

“…TNF-α affects the kynurenine pathway in patients with schizophrenia, as a positive correlation between the levels of TNF-α and KYN has been reported (35). TNF-α may accelerate the formation of KYN from the catabolism of TRP (35). We did not observe differences in TNF-α levels between negative and positive SARS-CoV-2 patients, however, we did find a correlation between TNF-α and KYN levels, similar to what has been reported for schizophrenia (35).…”

“…TNF-α may accelerate the formation of KYN from the catabolism of TRP (35). We did not observe differences in TNF-α levels between negative and positive SARS-CoV-2 patients, however, we did find a correlation between TNF-α and KYN levels, similar to what has been reported for schizophrenia (35). In this study, QUIN, 3-HK and KYN were significantly increased in patients with mild COVID-19.…”

Molecular pathways of major depressive disorder converge on the synapse

“…Kynurenic acid is a potent antagonist of peripheral and central nicotinic acetylcholine α-7 receptors, which are linked to cytokine production, inflammation, and the immune reaction [ 197 , 198 ], and are considered a potential drug target for depression treatment [ 197 – 199 ]. The kynurenine pathway is intertwined with numerous depression pathways, for example inflammation and immune cell activity, acute, chronic mild, and early-life stress [ 200 – 202 ], oxidative stress and mitochondrial function [ 203 , 204 ], and BDNF signaling [ 205 , 206 ] (Fig. 5 ).…”

Kynurenine pathway metabolites are associated with gray matter volume in subjects with schizophrenia

“…Kynurenine pathway (KP) is the major metabolic pathway for tryptophan (TRP) ( 10 , 11 ). Within central nervous system, TRP is degraded to KYN via indoleamine-2, 3-dioxygenase and tryptophan-2, 3-dioxygenase ( 11 – 14 ). The decrease in KYN may contribute to the development of chronic mild inflammation ( 8 , 15 ).…”