AUTHOR=De Picker Livia , Fransen Erik , Coppens Violette , Timmers Maarten , de Boer Peter , Oberacher Herbert , Fuchs Dietmar , Verkerk Robert , Sabbe Bernard , Morrens Manuel 

TITLE=Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02971

DOI=10.3389/fimmu.2019.02971

ISSN=1664-3224

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Method:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>p</italic> &lt; 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7–21.0, all <italic>p</italic> &lt; 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, <italic>p</italic> &lt; 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (<italic>r</italic> ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers (<italic>r</italic> ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (<italic>r</italic> = 0.5, <italic>p</italic> &lt; 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (<italic>r</italic> = 0.5, <italic>p</italic> &lt; 0.010).</p><p><bold>Conclusion:</bold> 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.</p>