Translating the Rosetta Stone of N-Acetylcysteine

Abstract

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 ( 1 Dean O. Giorlando F. Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011; 36: 78-86 PubMed Google Scholar ). Given the frequency of negative studies for established agents, the paucity of negative published studies is noteworthy. Glutamatergic Modulation of Auditory Information Processing in the Human BrainBiological PsychiatryVol. 71Issue 11PreviewAuditory 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 PDF A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with AutismBiological PsychiatryVol. 71Issue 11PreviewAn 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