Association between markers of oxidative stress and cognitive functioning in schizophrenia

High levels of oxidative stress have been implicated in the pathogenesis of schizophrenia. Our objectives were to review the association between oxidative stress markers and neurocognitive functioning in schizophrenia. Electronic search of MEDLINE, ProQuest, Scopus, and Google Scholar databases was carried out in September 2022 to identify relevant English language articles. Articles identified were grouped under the following themes: comparison of oxidative stress or antioxidant biomarkers between patients with schizophrenia and general population, association between biomarkers of oxidative stress and cognitive dysfunction in schizophrenia, and clinical trials evaluating the effect of antioxidant compounds on cognitive functioning in schizophrenia. We reviewed 36 eligible papers: 30 observational studies and 6 intervention trials. Marked heterogeneity was noted in patient population, oxidative stress markers examined, and cognitive measures. Majority (83.3%) of the observational studies were cross-sectional in design; half of them (50%) were conducted on chronic, stable, medicated patients. Most of the observational studies showed increased levels of oxidative stress biomarkers and decreased antioxidant activity in schizophrenia compared to controls. A significant positive association was noted between markers of antioxidant activity and cognitive performance in this group. Treatment trials of antioxidant agents showed positive but inconsistent evidence for benefits on cognitive measures and clinical symptomatology in schizophrenia. Our findings are broadly consistent with the redox imbalance hypothesis in schizophrenia. The significant associations noted between antioxidant markers and cognitive functioning may have key neurobiological and therapeutic implications.