Abstract
The aim of the study was the analysis of (1) the level of BAX,BCL2,BIRC6,CASP3, CASP9 apoptosis genes expression in schizophrenic patients and in the control group, and (2) the relationships between the genes expression level and the morphological and biochemical parameters, as well as the severity of psychopathological symptoms. The study included 21 patients diagnosed with schizophrenia according to ICD-10 and 26 healthy subjects. The following parameters were assessed: genes expression in peripheral blood lymphocytes, laboratory parameters and severity of psychopathological symptoms (using the PANSS). The expression of the BCL2 gene and the CASP3 gene was significantly higher in schizophrenic patients compared to the controls. A significant positive correlation was found between the BAX gene expression level and neutrophil, lymphocyte and monocyte counts as well as the severity of negative symptoms (PANSS-N), between BCL2 and CASP9 genes expression and the monocyte count, and between the CASP3 gene expression and the lymphocyte count. (1) Significantly higher expression of BCL2 and CASP3 genes in schizophrenic patients compared to the controls proves the intensification of the apoptosis process, fitting in the theory of increased apoptosis in the pathophysiology of schizophrenia. (2) Significant correlations between the BAX gene expression and differential blood count parameters (leucocyte, neutrophil, lymphocyte, monocyte count) in the group of schizophrenic patients suggest a relationship with immune dysregulation and confirm the presence of apoptosis in peripheral blood lymphocytes. (3) The BAX gene expression may be indicative of the severity of negative symptoms in schizophrenia. (4) The analysis of the intercorrelation of studied genes expression indicates that BAX and CASP3 genes were the most active in the apoptosis process in the study group.
Highlights
Schizophrenia is a severe, chronic mental disorder that primarily affects people in adolescence and early adulthood, the etiology and pathogenesis of which remains unclear [1]
The expression of the BCL2 gene and the CASP3 gene was significantly higher in schizophrenic patients compared to the controls
A significant positive correlation was found between the BAX gene expression level and neutrophil, lymphocyte and monocyte counts as well as the severity of negative symptoms (PANSS-N), between BCL2 and CASP9 genes expression and the monocyte count, and between the CASP3 gene expression and the lymphocyte count
Summary
Schizophrenia is a severe, chronic mental disorder that primarily affects people in adolescence and early adulthood, the etiology and pathogenesis of which remains unclear [1]. Among many theories concerning the etiopathogenesis of this disorder, there is a neurodevelopmental hypothesis of schizophrenia, formulated in the 1980s [2,3,4], with subsequent modifications and updates [5, 6] It assumes that already in the period of fetal and early childhood development, some abnormal changes occur in the central nervous system of people affected by this disorder [7]. In the process of the central nervous system maturation, there is a critical moment of synaptic pruning, which may proceed excessively and lead to a reduction in brain plasticity [8] It is accompanied by the elimination of some neurons in the apoptosis process, which is a genetically programmed sequence of biochemical processes induced by extrinsic or intrinsic initiator factors [9]. Increased apoptosis seems to be a key process in the neurodegenerative theory and is a link between this theory and the above-described neurodevelopmental hypothesis [19]
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