Effects of NAC on Symptoms of CHR Patients

The primary aim is to examine the effect of NAC on psychosis-like symptoms in CHR patients. Secondary aims are to examine the effect of NAC, in these patients, on the amplitude of the mismatch negativity (MMN), an electroencephalographic event-related potential (ERP) response to rare sounds among frequent ones; and the amplitude of the N400 semantic priming effect, an ERP response to unexpected compared to expected meaningful stimuli (e.g., words, pictures); both of which have been found to be reduced in both schizophrenia and the CHR state.

This will be a randomized, double-blind, placebo-controlled trial. Ninety CHR patients will take either NAC 2000 mg orally or placebo, daily for 8 weeks. Psychosis-like symptoms will be assessed at baseline, week 4 and week 8 using the Positive symptom score of the Scale of Psychosis-Risk Symptoms in the Structured Interview for Psychosis-Risk Syndromes. MMN amplitude and the N400 semantic priming effect will be measured at baseline and week 8. We hypothesize that patients will have more improvement in psychosis-like symptoms, and greater increases in MMN amplitudes and N400 semantic priming effects, after taking NAC vs. placebo. If we find that NAC improves psychosis-like symptoms and/or these neurophysiological biomarkers of the CHR state, this would support further research on NAC as a preventive treatment against psychosis.

Inclusion criteria

• meeting Criteria of Psychosis-Risk Syndromes (COPS) criteria on the Structured Interview for Psychosis-Risk Syndromes (SIPS)
• capacity to provide informed consent
• if female, participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure or have been post-menopausal for at least 1 year prior to screening OR participant is of child-bearing potential and agrees to use a medically approved method of birth control for the duration of the study

Exclusion criteria

• meeting criteria for any other DSM-5 diagnosis at the time of the study (except -personality disorder, nicotine use disorder, or other substance use disorder in full remission)
• concomitant or past neurological condition
• visual impairment which is not corrected to normal by prescription glasses history of reading disability
• past antipsychotic treatment at a therapeutic dose
• current treatment with a psychotropic medication except antidepressants on which the participants has been on a stable dose for at least 30 days.
• pregnancy (as identified on self-report and/or rapid urine pregnancy test) or intent to become pregnant according to self-report
• breastfeeding or plan to do so
• history of kidney stones
• current treatment with an antibiotic
• current treatment with nitroglycerin
• allergy to any ingredients in either the investigational product or placebo product