title: Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia.
abstract: Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission. KYNA levels were significantly lower in comparison with controls (N=45) throughout the study, whereas 3-HK did not differ from controls at admission and during therapy, but increased at remission. The KYNA/3-HK ratio and IL-4 levels, but not sIL-2R and IFN-α levels, were consistently decreased in schizophrenia patients at all analyzed time points. KYNA level and KYNA/3-HK ratio measured at admission correlated negatively with the duration of illness, whereas 3-HK level correlated negatively with the improvement of SANS score at discharge. sIL-2R level before treatment was positively linked with number of relapses. In the subgroup of patients with poor response to pharmacotherapy, treated with clozapine later on, initial KYNA level and the ratio KYNA/3-HK correlated negatively with number of relapses. Positive association of sIL-2R level with number of relapses was also evident in this subgroup. Furthermore, among these patients, starting IFN-α level was negatively linked with the improvement of total PANSS score at discharge. Presented here data support the concept of disturbed kynurenine pathway function in schizophrenia and suggest that assessment of KYNA and 3-HK levels during acute relapse might be useful in prediction of response to antipsychotic therapy. Deficit of peripheral KYNA and higher 3-HK levels could be associated with more severe symptoms of schizophrenia. Further studies with larger samples size are needed to validate our results.
authors.affiliation: Department of Psychiatry, Psychotherapy and Early Intervention, Medical University, Lublin, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Szymona
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zdzisińska
authors.affiliation: Department of Psychiatry, Psychotherapy and Early Intervention, Medical University, Lublin, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Karakuła-Juchnowicz
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kocki
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Martyna
authors.initials: M
authors.lastname: Kandefer-Szerszeń
authors.affiliation: Department of Psychiatry, Psychotherapy and Early Intervention, Medical University, Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Flis
authors.affiliation: Department of Applied Mathematics, Lublin University of Technology, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rosa
authors.affiliation: Laboratory of Cellular and Molecular Pharmacology, Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. emurbanska@poczta.onet.pl.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Urbańska
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D007736:Kynurenic Acid / Q000097:blood*; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D011569:Psychiatric Status Rating Scales; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012008:Recurrence; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D016898:Interferon-alpha; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; C005045:3-hydroxykynurenine; D007737:Kynurenine; D007736:Kynurenic Acid; D003024:Clozapine
keywords: Cytokines; Immune response; Kynurenines; Positive and negative symptoms; Psychoses