Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

Abstract

Objective The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ). Methods Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons. Results Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group ( p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores ( r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume ( r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)]. Conclusion Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.