NAC and Mitochondrial Abnormalities By Professor Michael Berk

Posted on: May 24, 2020
Last Updated: December 12, 2023

Professor Michael Berk is an NHMRC Senior Principal Research Fellow and Alfred Deakin Chair of Psychiatry at Deakin University and Barwon Health, where he heads the IMPACT Strategic Research Centre. He holds an Honorary position at both Melbourne and Monash University and is a highly cited researcher with over 800 published papers predominantly in mood disorders. His major interests are in the discovery and implementation of novel therapies, and risk factors and prevention of psychiatric disorders.

Author Quotes  

My argument is not that it [NAC] is not working in young people, it’s that the placebo response is so high in young people.

The whole idea that there are mitochondrial abnormalities in bipolar disorder is not a completely new thing, and if truth be told, it’s true across all psychiatric disorders.

Summary 

Prof Berk introduces this video excerpt with a look at a recent study on NAC and unipolar depression and discusses the primary finding of a very modest benefit.[Hoffer et al. 2013] 

He explains the problems behind data obtained in a designed study versus the true population of treated depressed individuals, and the challenge in determining how well a drug actually works. 

From study data, it appeared that age matters – middle-aged individuals were more likely to show a response to antidepressants compared with younger and older individuals, and Prof Berk explains his thoughts behind this. 

He moves onto the data from a small pilot study for NAC in tobacco use disorder which showed a robust result in the number of people who were able to stop smoking.[Prado et al. 2015] 

Continuing, he presents data on some other NAC studies, and evidence from a meta-analysis advocating efficacy of NAC in depression. 

Moving on, he discusses the relationship of mitochondria with brain activity in bipolar disorder, [Baxter Jr et al. 1985] and how VO2max varies with mania,[Caliyurt & Altiay. 2009] asking the question, “Is this a druggable target?” 

Moving on, he discusses the mitochondrial electron transport chain and presents some post-mortem data of the down-regulation of complex 1 in bipolar disorder.[Andreazza et al. 2010] 

Take-Home Points

  • Study results show an effect of NAC only in people with severe depression. 
  • NAC has no effect on idiopathic pulmonary fibrosis but does improve the quality of life for patients. 
  • Complex 1 of the mitochondrial electron transfer chain is dramatically down-regulated in bipolar disorder. 

Quiz


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References

  1. Hoffer ME, et al. Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo-controlled study. PLoS One. 2013;8(1):e54163.
  2. Prado E, et al. N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study. Redox Rep. 2015 Sep;20(5):215-22.
  3. Idiopathic Pulmonary Fibrosis Clinical Research Network, Martinez FJ, et al. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2093-101.  
  4. Baxter LR Jr, et al. Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18. Arch Gen Psychiatry. 1985;42(5):441-7.
  5. Caliyurt O, Altiay G. Resting energy expenditure in manic episode. Bipolar Disord. 2009 Feb;11(1):102-6.
  6. Andreazza AC, et al. Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch Gen Psychiatry. 2010 Apr;67(4):360-8. Erratum in: Arch Gen Psychiatry. 2010 Dec;67(12):1254. 
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