Grant: CIHR Fellowship

Psychotic disorders remain one of the most severe and disabling conditions associated with morbidity, mortality and disability. Individuals with clinical high risk (CHR) for psychosis have low-grade symptoms of psychosis and other difficulties that increase the risk of developing a "full-blown" psychotic disorder such as schizophrenia (SCZ). Given that only a proportion of CHR individuals go on to develop a psychotic disorder, efforts to refine our ability to identify those at highest risk are critical in providing appropriate interventions to improve outcomes in individuals who are most vulnerable. Measures such as event-related potentials (ERPs) or "brainwaves" offer objective reliable tools for predicting psychosis in individuals with CHR. N-acetylcysteine (NAC) is a natural health product shown to improve symptoms including hallucinations and delusions, and certain brainwave deficits, in SCZ. The brainwave that reflects how the brain apprehends how different concepts are related, called the N400, has been found to be deficient in CHR individuals. The P3b brainwave and the gamma steady state response reflect task-related attention and auditory processing, respectively, and have been found to be abnormal in SCZ and CHR patients. We hypothesize that CHR individuals taking NAC over 8 weeks will have more improved N400 effects, P3b and gamma steady-state response than those taking a placebo. We will examine if NAC is beneficial in improving symptoms in individuals with CHR and if this improvement is related to changes in their brainwaves. The results may identify ERP patterns associated with the effectiveness of NAC as a treatment for reducing psychotic symptoms in high risk individuals. This study may identify potentially effective treatments for individuals with CHR and may also help identify biomarkers of illness.