Abstract

Background Currently approved medications for schizophrenia are relatively ineffective for negative symptoms and cognitive impairment. N-Acetyl Cysteine (NAC) is a neuroprotective agent that improved general symptoms, cognitive impairment and negative symptoms in some but not all studies, but failed to improve positive symptoms in patients with schizophrenia. Progressive brain mass loss (PBML) has been consistently observed in early phase schizophrenia. NAC mitigates the deleterious effects oxidative stress, inflammation and glutamatergic excitotoxicity and these three pathological processes are hypothesized to contribute to PBML.

Methods In this study, we assessed the effects NAC (3600 mg/day) in a 52-week, double-blind, placebo controlled trial on symptoms, and cognition in early phase schizophrenia spectrum disorders (N = 60). In the context of the clinical trial, we explored the effects of NAC on brain morphology.

Results NAC significantly improved (time × group) PANSS total (F = 14.7, p < 0.001), negative (F = 5.1, p = 0.024) and disorganized thought (F = 13.7, p < 0.001) symptom scores. NAC failed to improve PANSS positive symptoms and BACS cognitive scores. In preliminary analyses, baseline right (r = −0.48, p = 0.041) and left (r = −0.45, p = 0.018) total cortical thickness, and thickness in other cortical regions, were associated with NAC related improvement in PANSS total scores, but NAC, as compared to placebo, did not significantly impact brain morphology over the study treatment period.