Abstract
Schizophrenia (SCZ) is a complex psychiatric disorder characterized by altered brain neurotrophic factor signaling. This study aimed to investigate the plasma levels of brain-derived neurotrophic factor (BDNF), its precursor proBDNF, and matrix metalloproteinase-9 (MMP-9) in SCZ patients and their relationships with clinical symptoms and lipid metabolism. Plasma levels of BDNF, proBDNF, and MMP-9 were measured in 105 SCZ patients and 76 healthy controls (HCs), the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status (CRDPSS), and the Positive and Negative Syndrome Scale (PANSS). SCZ patients exhibited significantly lower BDNF levels and higher proBDNF and MMP-9 levels compared to HCs. A negative correlation was observed between MMP-9 levels and CRDPSS negative symptom scores, PANSS negative subscale scores, and PANSS total scores. BDNF levels were positively correlated with total cholesterol (TC), while MMP-9 levels were negatively correlated with TC. The MMP-9-based discriminant model had high accuracy in distinguishing between HCs and SCZ patients, with an area under the curve (AUC) of 0.944 in the training set and 0.961 in the test set. Our findings suggest that MMP-9 and BDNF may be involved in the pathophysiology of SCZ and could serve as potential diagnostic biomarkers. The disrupted balance of BDNF and proBDNF, along with altered MMP-9 levels, may contribute to the clinical manifestation of SCZ, particularly in relation to negative symptoms and lipid metabolism.