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Title
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Immune and neuroendocrine trait and state markers in psychotic illness : decreased kynurenines marking psychotic exacerbations
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Author
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Abstract
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| Objective: Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology. Method: Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1-2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers. Results: Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5-17.5, all p < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNF alpha, and CCL2 and decreased QA and 3-HK (F8.7-21.0, all p < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, p < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (r >= |0.5|), while negative scale scores correlated inversely with IDO pathway markers (r >= |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (r = 0.5, p < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (r = 0.5, p < 0.010). Conclusion: The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness. |
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Language
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English
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Source (journal)
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Frontiers in immunology. - Place of publication unknown
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Frontiers in immunology
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Publication
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Place of publication unknown
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2020
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ISSN
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1664-3224
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DOI
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10.3389/FIMMU.2019.02971
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Volume/pages
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10
(2020)
, p. 1-12
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Article Reference
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2971
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ISI
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000510701300001
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Pubmed ID
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32010121
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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