Serum matrix metalloproteinase 9 (MMP9), tissue polypeptide antigen (TPA), pro-brain derived neurotrophic factor (probdnf), brain derived neurotrophic factor (BNDF), aquaporin 4 (AQP-4) levels in schizophrenia patients

Objective: It is known that schizophrenia's etiology includes synaptic connection dysfunction. Studies in the literature have emphasized the role of the neurovascular unit (NVU) and astrocytes in synaptic transmission, raising doubts about their function in the pathogenesis of schizophrenia. MMP-9, tPA, proBDNF, BDNF and AQP-4; proteins involved in NVU and astrocyte functions. In the current study, it was aimed to investigate the differences in serum levels of MMP-9, tPA, proBDNF, BDNF and AQP-4 in schizophrenia patients and healthy controls and to examine the variation of their levels with parameters such as disease severity and disease duration. Materials and Methods: This cross-sectional study consisted of 70 patients, 40 males and 30 females, who applied to the Afyonkarahisar Health Sciences University Faculty of Medicine psychiatry outpatient clinic between 30 May and 30 November 2022 and met the diagnostic criteria of schizophrenia according to DSM 5 criteria. 70 healthy volunteers without any psychiatric disease matched for age, sex, smoking and BMI were included. A sociodemographic and clinical data form was filled in after all participants were informed about the study and an informed consent form was obtained. In addition, the Positive and Negative Syndrome Scale (PANSS) was administered to the patients. After 12 hours of fasting, blood samples were taken from all participants to check serum MMP-9, tPA, proBDNF, BDNF and AQP-4 levels between 08:00 and 09:00 in the morning. Until biochemical analysis, blood samples were stored at -20 degrees. The data were analyzed using the SPSS 25 package program, and p 0.05 was regarded as significant. Results: As a result of the biochemical analysis, CRP (p=0.001), proBDNF/BDNF (p=0.015) levels were higher in schizophrenia patients compared to the control group; proBDNF (p<0.001), BDNF (p<0.001), tPA (p<0.001), AQP-4 (p<0.001) and MMP-9 (p=0.004) values were observed to be significantly lower than healthy controls. In the time-adjusted statistical analysis, it was observed that MMP-9 levels were actually significantly higher in schizophrenic patients (p=0.038), but there was a decrease in MMP-9 levels in pending blood samples since schizophrenia patients were included in the study earlier. ProBDNF and BDNF were positively correlated with AQP-4 (r= ,720; p<0,01) (r= ,557; p<0,01) and tPA (r= ,735; p<0,01) (r= ,689; p<0,01). In addition, the correlation between AQP-4 and tPA was positive and statistically significant (r= ,701; p<0,01). Conclusion: AQP-4 and tPA were found to be low in patients with schizophrenia. AQP-4 and tPA were positively correlated with proBDNF and BDNF. The underlying mechanism of low ProBDNF and BDNF in patients with schizophrenia may be astrocyte dysfunction and Neurovascular Coupling. Astrocyte dysfunction and Neurovascular Coupling may play an important role in the pathology of schizophrenia.