Galectin-3 mediated risk of inflammation in stable schizophrenia,with only possible secondary consequences for cognition

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 casecontrol 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-1βand 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-3and 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-βin 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;r^(2)=0.396).CONCLUSION The combined activity of Gal-3 and proinflammatory cytokines,TGF-βdownregulation and lower counts of leukocytes influence the SC duration.Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.