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Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia

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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.

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Acknowledgements

This study was supported by grants from Medical University in Lublin, DS 450/14, DS 450/15, DS 450/16, DS 192/14, and DS 192/15.

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Authors and Affiliations

  1. Department of Psychiatry, Psychotherapy and Early Intervention, Medical University, Lublin, Poland

    Kinga Szymona, Hanna Karakuła-Juchnowicz & Marta Flis

  2. Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland

    Barbara Zdzisińska & Martyna Kandefer-Szerszeń

  3. Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland

    Tomasz Kocki

  4. Department of Applied Mathematics, Lublin University of Technology, Lublin, Poland

    Wojciech Rosa

  5. Laboratory of Cellular and Molecular Pharmacology, Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland

    Ewa M. Urbańska

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  1. Kinga Szymona
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  2. Barbara Zdzisińska
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Correspondence to Ewa M. Urbańska.

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Szymona, K., Zdzisińska, B., Karakuła-Juchnowicz, H. et al. Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia. Neurotox Res 32, 17–26 (2017). https://doi.org/10.1007/s12640-017-9714-0

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