N-Acetylcysteine effects on glutathione and glutamate in schizophrenia: A preliminary MRS study

Yvonne S. Yang, Richard J. Maddock, Huailin Zhang, Junghee Lee, Gerhard Hellemann, Stephen R. Marder, Michael F. Green

Research output: Contribution to journalArticlepeer-review


N-acetylcysteine (NAC) is a commonly used antioxidant that may have beneficial effects for schizophrenia. In this double-blind, randomized, placebo-controlled preliminary study, 40 patients with schizophrenia or schizoaffective disorder were randomized to receive 2400 mg NAC daily or placebo over eight weeks to examine the effects of NAC on prefrontal magnetic resonance spectroscopy levels of glutathione and glutamate. Secondary outcomes included negative symptoms, cognition, and plasma glutathione levels. We found that NAC treatment was associated with increased glutathione (statistically significant) and decreased glutamate (trend-level) compared with placebo in medial prefrontal cortex but not dorsolateral prefrontal cortex. We also observed a baseline association between medial prefrontal cortex levels of glutathione and plasma reduced / oxidized glutathione ratios. No treatment effects on symptoms or cognition were observed. Taken together, these findings indicate that treatment with N-acetylcysteine may increase medial prefrontal cortical levels of glutathione after eight weeks of treatment. These changes in cortical levels of glutathione may serve as an early biomarker of later clinical change and may underlie the cognitive and symptomatic improvements reported in longer-term treatment studies.

Original languageEnglish
Article number111515
JournalPsychiatry Research - Neuroimaging
StatePublished - Sep 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by an institutional grant to YSY from the UCLA Friends of the Semel Institute for Neuroscience and Human Behavior. NAC Sustain and matching placebo tablets were supplied by Jarrows, Inc. Neither the UCLA Friends of the Semel Institue nor Jarrows, Inc. had input into study design, data collection, analysis, interpretation, writing of this report, decision to publish, or any other aspect of the study.

Publisher Copyright:
© 2022


  • Glutamate
  • Glutathione
  • Magnetic resonance spectroscopy
  • N-acetylcysteine
  • Oxidative stress
  • Schizophrenia


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