Association between serum non-enzymatic antioxidants and cognitive impairment in drug-naïve patients with schizophrenia

Cognitive impairment (CI) is a core feature of schizophrenia (SZ) and is strongly associated with poor functional outcomes. Oxidative stress and impaired antioxidant defense are implicated in the pathogenesis of CI across psychiatric disorders. But evidence in drug-naïve SZ remains limited. Serum levels of non-enzymatic antioxidants, including high-density lipoprotein cholesterol (HDL-C), albumin (ALB), total bilirubin (TBIL), and uric acid (UA), were measured in drug-naïve patients with SZ and healthy controls (HCs). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB), and psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS). Multivariable logistic regression models were used to evaluate associations between antioxidants and CI, with interaction and stratified analyses based on demographic and clinical variables. Linear regression analyses were used to evaluate the relationships between antioxidants and specific cognitive domains. A total of 219 drug-naïve patients with SZ and 101 HCs were included. CI was identified in 115 SZ patients (52.5%). Serum levels of HDL-C ( p = 0.004) and ALB ( p = 0.001) were significantly lower in patients with SZ than in HCs, whereas UA ( p = 0.001) was higher. Within the SZ group, patients with CI showed lower levels of HDL-C ( p = 0.019) and ALB ( p = 0.033) compared with those without CI. Logistic regression analyses showed that higher HDL-C (OR:0.30, 95% CI: 0.11–0.82) and ALB (OR:0.91, 95% CI: 0.84–0.99) levels were independently associated with lower odds of CI. In addition, linear regression analyses revealed that HDL-C ( p = 0.025) and ALB ( p = 0.008) were positively associated with overall cognitive performance, and ALB was also associated with verbal learning ( q = 0.007). This study suggests that higher serum HDL-C and ALB levels are associated with lower odds of CI and better overall cognitive performance in drug-naïve patients with SZ.