Grant: Project Grant

Schizophrenia is a chronic debilitating psychotic disorder. Identifying persons with "clinical high-risk" (CHR) symptoms which are like those of schizophrenia but less severe, and providing psychiatric care to these individuals has been shown to help prevent psychosis. Existing medications, however, have not been shown to reduce CHR patients' rates of developing psychosis and are associated with substantial side effect burden. Therefore, practice guidelines do not recommend current medications as routine treatment for the CHR state, and there is a need to identify new treatments for this condition. Research suggests that abnormal brain oxidative stress may contribute to schizophrenia, offering a potential novel treatment target in the CHR state. Oxidative stress is an excess of free radicals, which are generated from normal metabolism and environmental exposures, and can damage cells. Antioxidants in the body normally neutralize free radicals. Antioxidant deficiency could result in excess oxidative stress that damages brain cells, leading to schizophrenia. Recent studies suggest that N-acetylcysteine (NAC), a precursor of the most abundant brain antioxidant, glutathione, may be a safe, well-tolerated treatment for schizophrenia. In light of this, NAC may also reduce symptoms and brain abnormalities in CHR patients. We aim to examine whether, in CHR patients, NAC improves both psychosis-like symptoms and the mismatch negativity (MMN), a brain marker of schizophrenia and the CHR state. MMN is an EEG ("brainwave") response to rare sounds among frequent ones, which is reduced in both schizophrenia and the CHR state. Patients will take either NAC or placebo for 8 weeks in a randomized double-blind manner. We hypothesize that they will have symptom reductions and MMN increases after taking NAC vs. placebo. The ability of NAC to reverse symptoms and a biomarker of the CHR state would support further research on NAC as a preventive treatment against psychosis.