Glutathione, Oxidative Stress and N-Acetylcysteine (NAC) in Psychiatric Disorders – Prof Michael Berk

Posted on: October 30, 2016
Last Updated: November 10, 2023

Professor Michael Berk is currently an NHMRC Senior Principal Research Fellow and is Alfred Deakin Chair of Psychiatry at Deakin University and Barwon Health, where he heads the IMPACT Strategic Research Centre. He also is an Honorary Professorial Research Fellow in the Department of Psychiatry, the Florey Institute for Neuroscience and Mental Health and Orygen Youth Health at Melbourne University, as well as in the School of Public Health and Preventive Medicine at Monash University. His major interests are in the discovery and implementation of novel therapies, and risk factors and prevention of psychiatric disorders.

Author Quotes 

Glutathione is the brain’s primary antioxidant. 

About 100 years ago we knew this and it’s taken us 100 years to do something about it. Oxidative stress which can occur in childhood can alter your epigenetic signature and alter the way your proteins that your body produces are expressed. 

Summary and slides

There is reduced prefrontal cortex glutathione in Schizophrenia, Depression, and Bipolar disorder.

A paper published in 1934 by Looney and Childs called ‘The lactic acid and glutathione content of the blood of schizophrenic patients’ first raised the hypothesis of oxidative stress and mitochondrial dysfunction in schizophrenia.

Oxidative stress alters your epigenetic signalling so can alter DNA methylation, change how genes are transcribed, and ultimately protein expression. 

N-Acetylcysteine (NAC) has robust effects on neurogenesis and apoptosis, directly reverses mitochondrial dysfunction, has potent anti-inflammatory effects and indirect effects on dopamine and glutamate.

Presenting preclinical data, Professor Berk concludes this presentation with a discussion of the role of NAC in mitochondrial toxicity, methamphetamine-induced apoptosis, and the effects on cognition by mitochondrial dysfunction. 

Take-home Points  

  • Glutathione, the brain’s primary antioxidant, is decreased in schizophrenia and increased by NAC 
  • Altered epigenetic signalling through oxidative stress may explain the relationship between childhood stress and vulnerability to developing adult illnesses 
  • C-reactive protein, interleukin-6, and TNF-[Symbol] are important immune markers 


Learn more

  1. Applications of N-Acetylcysteine (NAC) – From Addiction to Autism By Prof Berk
  2. N-Acetylcysteine (NAC) in Schizophrenia and Bipolar Disorder- Prof Michael Berk
  3. Oxidative and Inflammatory Biomarkers as Targets for Novel Therapies – Prof Michael Berk
  4. Effect of the Mediterranean Diet On Depression By Prof Michael Berk
  5. Early Life Nutrition and Neurodevelopment by Prof Michael Berk
  6. The Role of the Microbiome and Diet in Depression by Prof Michael Berk
  7. Healthy Diet vs Nutraceuticals in Depression by Prof Michael Berk
  8. Effect of Diet and Lifestyle Changes in Depression by Prof Michael Berk


  1. Gawryluk, J. W., Wang, J. F., Andreazza, A. C., Shao, L., & Young, L. T. (2011). Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. International Journal of Neuropsychopharmacology, 14(1), 123-130.
  2. Looney, J. M., & Childs, H. M. (1934). The lactic acid and glutathione content of the blood of schizophrenic patients. Journal of Clinical Investigation, 13(6), 963.