Manuel Morrens1, Livia De Picker2, Jarl K Kampen3, Violette Coppens2. 1. Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Centre Duffel, Duffel, Belgium. Electronic address: manuel.morrens@uantwerpen.be. 2. Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Centre Duffel, Duffel, Belgium. 3. Faculty of Medicine and Health Sciences, Epidemiology and Medical Statistics, University of Antwerp, Antwerp, Belgium.
Abstract
INTRODUCTION: The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD). Empirical evidence for such immune-related KP shifts in SSD has however resulted in divergent findings. METHODS: We conducted a systematic literature search in PubMed. Thirty papers (total number of patients n = 1506; controls: n = 1432) reported on peripheral concentrations of KP metabolites in SSD patients versus controls. Six KP metabolites were included in a meta-analysis, with secondary analysis of covariate and subgroup effects of patients' symptomatic state, age and duration of illness. RESULTS: Tryptophan (SMD: -0.30; p = .003) and Xanthurenic Acid (SMD: -0.80; p < .001) were significantly decreased in SSD compared to controls, while Quinolinic Acid (SMD: -0.40; p = .08) and Kynurenic Acid (SMD: -0.39; p = .04) were only significantly decreased in patients with acute or highly symptomatic illness. Finally, in relatively older patient cohorts Kynurenine (SMD: -0.31; p = .02) and Kynurenic Acid (SMD: -0.40; p = .002) were found to be decreased. CONCLUSION: A partial downregulation of the KP is observed in SSD patients, in particular during acute symptomatic states and in older age, effects that were independent from each other. In contrast, younger and stable or remitted patients display limited to no KP metabolite abnormalities. The current meta-analysis illustrates the dynamic nature of KP abnormalities. It should be noted that all included studies investigated peripheral KP metabolites, which do not necessarily reflect central KP metabolite abnormalities in schizophrenic patients.
INTRODUCTION: The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD). Empirical evidence for such immune-related KP shifts in SSD has however resulted in divergent findings. METHODS: We conducted a systematic literature search in PubMed. Thirty papers (total number of patients n = 1506; controls: n = 1432) reported on peripheral concentrations of KP metabolites in SSDpatients versus controls. Six KP metabolites were included in a meta-analysis, with secondary analysis of covariate and subgroup effects of patients' symptomatic state, age and duration of illness. RESULTS:Tryptophan (SMD: -0.30; p = .003) and Xanthurenic Acid (SMD: -0.80; p < .001) were significantly decreased in SSD compared to controls, while Quinolinic Acid (SMD: -0.40; p = .08) and Kynurenic Acid (SMD: -0.39; p = .04) were only significantly decreased in patients with acute or highly symptomatic illness. Finally, in relatively older patient cohorts Kynurenine (SMD: -0.31; p = .02) and Kynurenic Acid (SMD: -0.40; p = .002) were found to be decreased. CONCLUSION: A partial downregulation of the KP is observed in SSDpatients, in particular during acute symptomatic states and in older age, effects that were independent from each other. In contrast, younger and stable or remitted patients display limited to no KP metabolite abnormalities. The current meta-analysis illustrates the dynamic nature of KP abnormalities. It should be noted that all included studies investigated peripheral KP metabolites, which do not necessarily reflect central KP metabolite abnormalities in schizophrenicpatients.
Authors: M Morrens; C Overloop; V Coppens; E Loots; M Van Den Noortgate; S Vandenameele; M Leboyer; L De Picker Journal: Mol Psychiatry Date: 2022-04-28 Impact factor: 15.992
Authors: Abbas F Almulla; Asara Vasupanrajit; Chavit Tunvirachaisakul; Hussein K Al-Hakeim; Marco Solmi; Robert Verkerk; Michael Maes Journal: Mol Psychiatry Date: 2022-04-14 Impact factor: 15.992
Authors: Katrien Skorobogatov; Livia De Picker; Robert Verkerk; Violette Coppens; Marion Leboyer; Norbert Müller; Manuel Morrens Journal: Front Immunol Date: 2021-09-23 Impact factor: 7.561
Authors: Korrapati V Sathyasaikumar; Francesca M Notarangelo; Deanna L Kelly; Laura M Rowland; Stephanie M Hare; Shuo Chen; Chen Mo; Robert W Buchanan; Robert Schwarcz Journal: Pharmaceuticals (Basel) Date: 2022-08-15