Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders

Alan Breier, Emily Liffick, Tom A. Hummer, Jenifer L. Vohs, Ziyi Yang, Nicole F. Mehdiyoun, Andrew C. Visco, Emmalee Metzler, Ying Zhang, Michael M. Francis

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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. Conclusions: These results replicate some but not all previous findings of NAC efficacy. Preliminary results suggest that NAC's symptom effects may be related to structural integrity, but NAC failed to demonstrate treatment effects on longitudinal measures of brain morphology. ClinicalTrials.gov Identifier: NCT01339858

Original languageEnglish (US)
Pages (from-to)395-402
Number of pages8
JournalSchizophrenia Research
StatePublished - Sep 2018
Externally publishedYes


  • Cognitive impairment
  • Early phase schizophrenia spectrum disorders
  • N-acetyl cysteine
  • Negative symptoms
  • Positive symptoms
  • Progressive brain mass loss

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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