BACKGROUND: Schizophrenia, a severe mental disorder with complex pathophysiology, involves neurotrophic factors, which play crucial roles in neurodevelopment and neuroplasticity. This study investigated NGF-β and BDNF levels in chronic schizophrenia and their association with clinical symptoms, cognitive function, and 1,25(OH)₂D levels. METHODS: In this cross-sectional study, 72 male patients with chronic schizophrenia and 70 matched healthy controls were enrolled. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The serum levels of NGF-β, BDNF, and 1,25(OH)₂D were measured. RESULTS: Serum levels of NGF-β (F = 35.239, P <
0.001) and BDNF (F = 12.669, P <
0.001) were significantly decreased in patients with chronic schizophrenia compared to healthy controls. NGF-β levels were negatively correlated with PANSS negative symptoms (beta = -0.205, t = -2.098, P = 0.040) and positively correlated with 1,25(OH)₂D levels (r = 0.324, P = 0.006). Decreased serum BDNF concentrations were negatively correlated with language deficits (beta = -0.301, t = -2.762, P = 0.007). Significant associations were observed between chronic schizophrenia and reduced levels of NGF-β (B = 1.040, P <
0.001, RR = 2.829, 95% CI: 2.101-3.811) and BDNF (B = 0.526, P = 0.001, RR = 1.692, 95% CI: 1.241-2.306). CONCLUSIONS: Our findings indicated that NGF-β and BDNF levels were altered in chronic schizophrenia and were associated with clinical symptoms and vitamin D metabolism. These results provided new insight into the etiology of schizophrenia.