Oxidative stress markers in at-risk individuals for psychosis: A systematic review and meta-analysis

Schizophrenia is a highly heritable psychiatric disorder that is often accompanied by various somatic illnesses. Oxidative stress is a key factor in its pathophysiology, with evidence suggesting that even individuals at risk for psychosis may exhibit impaired oxidative balance, although findings remain inconsistent. In this study, we aimed to investigate oxidative stress markers in individuals at risk for psychosis to evaluate their potential role in disease predisposition. Additionally, we conducted meta-analyses on studies examining GPx and SOD levels and enzyme activities.

A literature search was performed in PubMed, Scopus, and Web of Science using relative keywords. Studies were included if they evaluated oxidative stress markers in first or second-degree relatives of individuals with psychosis, included healthy controls (HCs) for comparison and were written in English. Studies comparing the levels and enzyme activity of GPx and SOD were evaluated using meta-analyses with the random-effects method.

Seven studies met the inclusion criteria for systematic review, with meta-analyses conducted on five studies assessing GPx levels and four studies assessing SOD levels. No significant differences were observed in GPx activity and levels between relatives of individuals with psychosis and HCs (Hedges' g = 0.18, 95 % CI = -0.50 - 0.85, p = 0.61), with high heterogeneity (I² = 87 %). Similarly, no significant differences in SOD activity and levels (Hedges' g = -0.71, 95 % CI = -1.65 - 0.23, p = 0.14), with high heterogeneity (I² = 90 %).

Our review highlights evident differences in oxidative stress processes in individuals at risk for psychosis, despite no single marker serving as a definitive indicator. Future longitudinal studies with large, homogeneous samples are needed to confirm these findings.