Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Sep 19, 2022; 12(9): 1183-1193
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1183
Galectin-3 mediated risk of inflammation in stable schizophrenia, with only possible secondary consequences for cognition
Slavica Minic Janicijevic, Ivan P Jovanovic, Nevena M Gajovic, Milena M Jurisevic, Monojit Debnath, Nebojsa N Arsenijevic, Milica M Borovcanin
Slavica Minic Janicijevic, University of Kragujevac, Faculty of Medical Sciences, Kragujevac 34000, Serbia
Ivan P Jovanovic, Nevena M Gajovic, Nebojsa N Arsenijevic, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Milena M Jurisevic, Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Monojit Debnath, Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore 560029, India
Milica M Borovcanin, Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Author contributions: Minic Janicijevic S and Borovcanin MM presented the design of this project, recruited the participants, performed the psychological and somatic assessment, collected the samples for laboratory measurements, structured the manuscript and incorporated all parts of the manuscript; Jovanovic IP, Gajovic NM and Arsenijevic NN performed the cytokine measurements; Jurisevic MM and Borovcanin MM did the statistical analysis and prepared tables and figures; All authors, especially Debnath M, additionally searched the literature and provided new insights into specific areas of their expertise, made a final revision of the manuscript, and corrected the figures; All authors read, discussed, and approved the final version of the manuscript.
Supported by Ministry of Science and Technological Development of the Republic of Serbia, No. 175069; and Faculty of Medical Sciences, University of Kragujevac, No. JP15-05.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Kragujevac Clinical Centre.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Minic Janicijevic S, Jovanovic IP, Gajovic NM, Jurisevic MM, Arsenijevic NN and Borovcanin MM has received research funding from Ministry of Science and Technological Development of the Republic of Serbia, No. 175069 and Faculty of Medical Sciences, University of Kragujevac, No. JP15-05. Debnath M declared no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Milica M Borovcanin, MD, PhD, Associate Professor, Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia. milicaborovcanin@yahoo.com
Received: April 20, 2022
Peer-review started: April 20, 2022
First decision: May 30, 2022
Revised: June 14, 2022
Accepted: August 10, 2022
Article in press: August 10, 2022
Published online: September 19, 2022
Abstract
BACKGROUND

Evidence suggests that cytokines cause immune disturbances, shape immunological sequelae later in life, and modulate the risk of schizophrenia (SC). Galectin-3 (Gal-3), a multifaceted molecule of the glycan family, is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes, which are major producers of cytokines. We have previously reported elevated serum Gal-3 levels in stable SC patients. However, Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.

AIM

To investigate the relationship between serum Gal-3 levels and cognitive performance, serum cytokines, and white blood cell count in three-month stably treated SC patients.

METHODS

Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this case-control and correlational study. Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment. The results of previously measured serum levels of Gal-3, interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), tumor necrosis factor-alpha (TNF-α), IL-6 and IL-17 were used for further statistical analyses, and IL-4, IL-23, IL-1β and transforming growth factor-beta (TGF-β) were now additionally measured with a sensitive enzyme-linked immunosorbent assay. The number of leukocytes in the blood and the percentage of neutrophils, lymphocytes, and monocytes were determined with a standardized routine measurement procedure (Sysmex Technology). Statistical analyses were performed using SPSS 20.0 software.

RESULTS

We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients. A positive correlation was found between the levels of Gal-3 and TNF-α (r = 0.476; P = 0.012), Gal-3 and IL-23 (r = 0.417; P = 0.031), and Gal-3 and sST2 (r = 0.402; P = 0.038). The binary logistic model, which included all nine cytokines measured in this patient sample, indicated the particular role of Gal-3 and TGF-β in the duration of SC. In the stabilization phase of SC, we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes (r = -0.449; P < 0.019). Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose (F: 4.467; P < 0.045; r2 = 0.396).

CONCLUSION

The combined activity of Gal-3 and proinflammatory cytokines, TGF-β downregulation and lower counts of leukocytes influence the SC duration. Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.

Keywords: Schizophrenia, Galectin-3, Cytokines, Leukocytes, Antipsychotics

Core Tip: In clinical sampling, there is an urge to place the results of biological measurements in a much broader context. Elevated serum galectin-3 (Gal-3) levels in schizophrenia (SC) have not been studied in relation to other peripheral biomarkers and subsequent neuroinflammation. We found that Gal-3 contributes to ongoing peripheral systemic inflammation and disease duration in patients with SC. All of this may be an underlying indirect immunometabolic mechanism for cognitive performance in patients with SC.