Tuesday 17 April 2012

Functional connectivity, NAC & schizophrenia

I promise that I am not getting obsessed with N-acetyl-cysteine (NAC) nor am I moving my focus from autism research to schizophrenia research despite recent posts. It just so happened that I stumbled upon this paper by Carmeli and colleagues* (full-text) recently and the needle on my interest-o-meter started to register something potentially important.

Indeed, there were several things about this paper which just made it seem right to comment on it: the use of that dark art, EEGs, the small participant group with schizophrenia, the NAC thing and the tie-up with glutathione. My previous posts on the potential for overlap between schizophrenia and autism and the significantly over-represented paper discussion serve as reminders that although discrete conditions, the words 'cut from the same cloth' in a biochemical sense might not necessarily be an inappropriate saying.

The paper is available to all but a summary:

  • N-acetyl-cysteine (NAC) was given to participants diagnosed with DSM-IV schizophrenia (N=11) in a randomised, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). Yes, you saw right, the trial only included 11 participants which dropped to 8 participants when all was said and done. Having said that, this group (I think) were involved in a larger trial of NAC and schizophrenia undertaken by some of the authors.
  • Resting EEGs were carried out at baseline, 2 months (treatment cross-over point) and 4 months (study end). I am not an EEG Jedi Master so an easy description I cannot give [said in best Yoda voice] of what was done aside from pasting from the article: "..whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs". I think this means that neural synchrony was a big part of the analysis but don't quote me on that.
  • After some statistical wizardry, the results suggested that NAC supplementation seemed to affect EEG synchronisation in a couple of brain areas and despite the small participant numbers, the results seemed to be fairly similar across individual participants at least in relation to a few of those brain areas. From a behavioural perspective, the results also seemed to tie into other findings of issues with executive functions and attention noted in people with schizophrenia.

Despite the small sample size, these are interesting findings. Interesting because of the implications for schizophrenia and brain function which kinda follows on from the recently discussed study on schizophrenia and dietary intervention from a few years back. I know synchronisation is not the same as cerebral blood flow, but the link is the suggestion that at least some of the brain findings in schizophrenia might, just might, be functional rather than just structural and hence partially reversible in the same way that pharmacotherapy such as neuroleptics are used. A similar thing also to what Dr Michael Merzenich discussed in this recent piece in Nature on neuroplasticity and brain training. I would hasten to add that I am reserving judgement on the schizophrenia - brain training link until more substantial evidence is forthcoming.

As to the involvement of NAC and glutathione in schizophrenia, well this paper by Olivia Dean and colleagues** (full-text) seems to sum it up quite well. That and a post by Dr Deans with a rather appropriate title (I have a NAC for that). I also think back to the study looking at possible biomarkers for schizophrenia and their finding of issues with cystine (the dimer of cysteine) and can't help but think that there might be something crucial there which really should be looked at with greater assiduity.

* Carmeli C. et al. Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial. PLoS ONE. February 2012.
DOI: 10.1371/journal.pone.0029341

** Dean O. et al. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. Journal of Psychiatry & Neuroscience. 2011; 36: 78-86.
DOI: 10.1503/jpn.100057

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