Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review

Abstract

Background: In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory. Methods: A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites. Results: Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients. Of these articles: Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway). Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway. Only one study discovered correlations between IL-8 and the kynurenine pathway. Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway. Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia.

The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

“…However, is there a proinflammatory phenotype in SCZ? Post-mortem and clinical studies show an increase in pro-inflammatory markers in people with SCZ compared to controls (Fillman et al, 2016;Sekar et al, 2016;Boerrigter et al, 2017;Lesh et al, 2018;Goldsmith and Rapaport, 2020;Pedraz-Petrozzi et al, 2020). Moreover, there is evidence for elevated levels of cytokines in blood samples from people with SCZ, whether they are medication-naive or receiving antipsychotic treatment, during episodes of psychosis (McKernan et al, 2011;De Picker et al, 2019;Mondelli et al, 2020;Steiner et al, 2020).…”

Efficacy and safety of Jie-du-qing-nao granules for first-episode schizophrenics: study protocol for a randomized controlled trial

“…At present, there were numerous studies suggesting that the in ammatory activation was associated with schizophrenia. The main in ammatory factors involve TNF-α, IL-6, IL-1β [14]. A meta-analysis showed that TNFα, IL-6 and IL-1β were elevated in patients with schizophrenia [14].…”

“…The main in ammatory factors involve TNF-α, IL-6, IL-1β [14]. A meta-analysis showed that TNFα, IL-6 and IL-1β were elevated in patients with schizophrenia [14]. BDNF is a neurotrophic factor that plays an important role in neuronal transport, modulation, and plasticity [15].…”

Negative and positive disorders of schizophrenia (issues of co-dependence, psychopathology and pathogenesis)

“…Вместе с тем развитие этих патологических дименсий (позитивные/негативные расстройства) ассоциировано с двумя различными, хотя и взаимосвязанными молекулярными механизмами. В основе первого из них, определяющего развитие обратимых позитивных симптомокомплексов, лежит дисбаланс в нейротрансмиссии, формирующийся вследствие влияния провоспалительных цитокинов, синтезируемых активированной микроглией, на катаболизм триптофана и смещения его в сторону кинуренового пути [37,38]. В основе второго механизма, определяющего развитие прогрессирующих и относительно необратимых негативных изменений, лежит процесс нейродегенации, связанный с синтезом активированной микроглией большого количества нейротоксических метаболитов: активных форм кислорода, азота, глутамата, аспартата и др., что ведет к повреждению нейронов и глии, потере функционирующих синапсов и нарушению функционирования нейронных сетей [39,40].…”