: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities. The activities of plasma superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls. Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities and MDA levels were measured at baseline and during follow-up. Compared with healthy controls, the patients showed higher activities of SOD and CAT, but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with bodyweight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparison between WG group and non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up. These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.

Objective Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD), and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. Methods We examined this hypothesis in 183 drug-naïve first episode (DNFE) SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD) and SOD activities and BDNF levels in these patients and compared their levels to 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. Results After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline, but not correlated after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the RBANS only in high BDNF subgroup. Conclusions Our longitudinal study suggests that risperidone can enhance SOD activity and that in combination with higher baseline BDNF levels acting in a permissive role can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients getting risperidone treatment.

Brain-derived neurotrophic factor (BDNF) is reported to be involved in cognitive decline in patients with schizophrenia (SZ). Previous studies have found that cognitive deficits remain stable during the chronic disease phase in SZ, but the findings were inconsistent. The role of BDNF in cognitive deficits at different stage of illness remains unclear. This study aimed to examine the effect of BDNF polymorphisms on cognitive deficits in drug-naïve first-episode (DNFE) patients and chronic patients with SZ. 262 DNFE patients, 844 chronic patients, and 1043 healthy controls were recruited to compare 4 polymorphisms in BDNF gene and cognitive function. We found that there was no significant difference in genotype and allele frequencies between SZ patients and controls. However, they were closely related to cognitive functioning. BDNF rs2030324 polymorphism played a strong role in language performance only in DNFE patients with SZ. The language index of DNFE patients with rs2030324 TT and TC genotypes was worse than that of chronic patients, but there was no significant difference in CC genotypes between DNFE and chronic patients. Rs6265 had no significant effect on cognitive functioning in patients and controls. Our result suggests BDNF gene polymorphisms were related to different domains of cognitive function at the different stage of SZ, especially language in DNFE patients.