Oxidative stress markers during the psychotic transition

Ultra-high-risk state (UHR) concept was initially applied to promote the early detection of young help-seeking patients with higher risk of psychotic transition. However, most UHR individuals do not evolve to psychosis, stressing the need for biomarkers allowing the prediction of the transition. Substantial evidence suggest that redox dysregulation plays a major role in the pathophysiology of psychotic disorders. The aim of this study is to explore the relationship between the evolution of blood oxidative stress markers in UHR individuals. Blood samples were collected from 48 UHR individuals at their first visit and 12 months later for those who did not convert to psychosis (UHR-NC), or at the time of the transition for the converters (UHR-C). Markers for redox dysregulation, including the glutathione antioxidant system, superoxide dismutase, thioredoxin, TBARS, macrophage migration inhibitory factor, peroxiredoxin-4, MMP9 and sRAGE, were assessed in erythrocytes, serum and plasma. Statistical analyses revealed a combination of peripheral redox markers associated with the risk of transition to psychosis. These markers were able to discriminate between UHR-C and UHR-NC subjects at baseline. A decrease in blood levels of peroxiredoxin-4, an antioxidant enzyme, was associated with a lower risk of transition. GPx activity and TBARS levels were associated with the later severity of symptoms during the course of psychosis. These findings suggest the interest of peripheral biomarkers of oxidative stress to monitor the risk of psychosis. Overall, these findings hold promises for early detection and argue for the development of treatments targeting redox pathways in psychosis.