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Commentary| Volume 71, ISSUE 11, P935-936, June 01, 2012

Translating the Rosetta Stone of N-Acetylcysteine

  • Olivia M. Dean
    Affiliations
    School of Medicine, Deakin University, Victoria, Australia

    Department of Psychiatry, The University of Melbourne, Geelong, Victoria, Australia

    Mental Health Research Institute, The University of Melbourne, Victoria, Australia
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  • Ashley I. Bush
    Affiliations
    Mental Health Research Institute, The University of Melbourne, Victoria, Australia
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  • Michael Berk
    Correspondence
    Address correspondence to Michael Berk, M.D., Ph.D., Deakin University, Geelong, Victoria, Australia
    Affiliations
    School of Medicine, Deakin University, Victoria, Australia

    Department of Psychiatry, The University of Melbourne, Geelong, Victoria, Australia

    Mental Health Research Institute, The University of Melbourne, Victoria, Australia

    Orygen Youth Health Research Centre, Parkville, Victoria, Australia
    Search for articles by this author
      The history of the field of biological psychiatry can be cynically encapsulated by the quest to reverse engineer serendipitous clinical findings. The role of monoamines in depression, dopamine in schizophrenia, and second messengers in bipolar disorder have all been reversed engineered from understanding the effects of tricyclics, antipsychotics, and lithium, respectively. In this context, the emergence of N-acetylcysteine (NAC) as a potential therapeutic modality provides a dual opportunity: a novel therapy and a key to unlocking the pathophysiology of the targeted disorders. One of the perplexing and curious things about NAC is that it appears to be of potential value for a multitude of phenomena in a diversity of seemingly disparate disorders. Mirroring what we have seen with atypical antipsychotics and even antidepressants, efficacy patterns of NAC show little respect for the chapter structure of the DSM-IV system. Positive trials are reported for negative and extrapyramidal symptoms in schizophrenia, depression in bipolar disorder, cocaine craving, smoking cessation, trichotillomania, and gambling (
      • Dean O.
      • Giorlando F.
      • Berk M.
      N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action.
      ). Given the frequency of negative studies for established agents, the paucity of negative published studies is noteworthy.
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      Linked Article

      • Glutamatergic Modulation of Auditory Information Processing in the Human Brain
        Biological PsychiatryVol. 71Issue 11
        • Preview
          Auditory mismatch negativity (MMN) and P300 event-related potentials (ERPs) are reduced in schizophrenia patients and healthy volunteers administered the N-methyl-D-aspartate glutamate receptor antagonist, ketamine. In rodents, N-acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of N-methyl-D-aspartate receptor antagonists. On the basis of these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans.
        • Full-Text
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      • A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism
        Biological PsychiatryVol. 71Issue 11
        • Preview
          An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant, in the treatment of behavioral disturbance in children with autism.
        • Full-Text
        • PDF