Association of nitric oxide and neurotrophin-3 with cognitive dysfunction in schizophrenia spectrum disorders (SSD): A cross-sectional comparative study

Background: Schizophrenia is a chronic psychiatric disorder affecting about 1% of the population, with cognitive decline as a debated feature. Dysregulation of synaptic plasticity plays a key role in its pathogenesis. Neurotrophin-3 (NT-3), a polypeptide growth factor, and nitric oxide (NO), an intra- and inter-cellular messenger, influence synaptic plasticity. Addenbrooke’s cognitive examination-III (ACE-III) and Montreal cognitive assessment (MoCA) are bedside, sensitive cognitive assessments used to evaluate cognitive function. Aim: This study aimed to explore the association of serum NO, NT-3, and cognitive performance in schizophrenia. Methods: A hospital-based cross-sectional comparative study was conducted in the Department of Biochemistry, in collaboration with the Department of Psychiatry, at our tertiary care hospital. The study included 43 drug-naïve/free schizophrenia patients, and 43 age-, gender-, and BMI-matched controls. Cognitive assessments (ACE-III, MoCA) and estimation of serum NT-3 and NO levels using enzyme-linked immunosorbent assay (ELISA) were performed at the time of recruitment. Results: Serum NT-3 and NO levels were significantly lower in schizophrenia patients, along with decreased ACE-III and MoCA scores compared with controls. A significant positive correlation was observed between serum NO and NT-3 concentrations, also between ACE-III and MoCA scores. Serum NO, NT-3 levels correlated positively with cognitive scores in cases. Serum NT-3 and NO levels were significantly associated with schizophrenia, though the associations were weaker than those observed for ACE-III and MoCA. Conclusion: ACE-III and MoCA scores were strongly associated with cognitive impairment in schizophrenia, whereas serum NT-3 and NO showed modest association. Larger, longitudinal studies are needed to validate as biomarkers of cognitive decline.