NAC for autism: a case study

NAC or N-acetlycysteine has appeared a couple of times on this blog in relation to both autism (see here) and schizophrenia (see here). Not bad for a compound which more readily finds a home in modern medicine following paracetamol (acetaminophen) overdose or as a consequence of its mucolytic properties.

As one might imagine, the autism link is of particular interest to this blog, focused specifically on the findings of Hardan and colleagues* when it came to putting NAC to the [albeit preliminary] experimental test. The results by the way were encouraging for at least some parts of the presentation of childhood autism with the promise of more to come.

As a sort of follow-up to the Hardan paper, I'm talking today about a case report offered by Ghanizadeh & Derakhshan** (open-access) highlighting a little more individual detail following the use of NAC with an 8-year old boy diagnosed with autism. I know the word 'case report' sends a shudder down many a scientific shoulder, but as I've said quite a few times before, we ignore the N=1 in autism at our peril given the wide, wide heterogeneity present and all that associated comorbidity to contend with. Real personalised medicine you might say.

If I have managed to persuade you to listen to the rest of my ramblings on this paper and topic, there are a few important points to make about/from the Ghanizadeh paper:

• From the description provided, the child in question seemed quite floridly autistic with the important add-ons of hyperactivity and inattention present from an early age. Although we aren't told what exactly it means, the authors note: "His laboratory examination was unremarkable".
• Oral NAC (800mg per day) was begun as part of another trial by the authors to counteract nail-biting***. As unusual as it might sound, mail-biting has been a focus of some NAC research coincident to the presence of anxiety.
• Indeed, the boy's nail-biting behaviours did seem to subside alongside the installation of NAC but perhaps of greater interest were the reports that "there was a marked reduction in his autism symptoms 30 days after the onset of NAC administration". OK so this report did come from the boy's parents, and without causing any offence, the issue of objectivity might come into play.
• The types of 'changes' reported however were in core areas such as his verbal skills, social interaction and a quite unusual preoccupation with having his hair cut (I say unusual because a visit to the barber or hairdresser described by many parents about their child with autism, is often characterised by entirely the opposite reaction).
• Aside from "a mild abdominal pain" the authors importantly say that "nothing worsened after the administration of NAC" which I take to indicate that side effects were minimal over the course of the intervention.

I should have perhaps mentioned at the beginning that there is some sound logic why NAC might have some effect on cases of autism. The amino acid cysteine as well as containing sulfur, so potentially tied into to that most forgotten areas of autism research sulfur chemistry (see here), is also the precursor to another important compound, glutathione. I know my regular readers are probably getting a little bored of me going on about this 'elephant in the room' and in particular that glutathione overview paper by Main and colleagues (see here) but a possible link is a possible link.

I was also interested to read the authors' discussions on how NAC might also have the ability to decrease "high glutamate levels". As any good biochemist will tell you, glutathione, which is dependent on cysteine, is a tripeptide which also incorporates the amino acids glycine and glutamate into its triadic manufacture. From that point of view, circumstances where any of the three amino acids were low or not optimally biologically available might affect the production of glutathione. If that happens to mean you have low cysteine levels, glutathione would be low but also this might mean levels of glutamate or glycine could be higher as a result of not being used up to make glutathione. Glutamate is another compound finding some significant interest with regards to autism and conditions presenting with autistic symptoms.

Reiterating that the Ghanizadeh paper is a case report, I do find there to be some interesting observations reported. With my speculating hat on, I do wonder whether that link with nail-biting and onwards anxiety suggested for NAC might also be part and parcel of the effect observed in this case given the quite considerable link suggested between autism and anxiety (see here)?

And by the looks of things NAC is in the research ascendancy perhaps even with a prophylactic effect****...

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* Hardan AY. et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014.

** Ghanizadeh A & Derakhshan N. N-acetylcysteine for treatment of autism, a case report. J Res Med Sci. 2012 Oct;17(10):985-7.

*** Ghanizadeh A. et al. N-acetylcysteine Versus Placebo for Treating Nail Biting, A Double Blind Randomized Placebo Controlled Clinical Trial. Antiinflamm Antiallergy Agents Med Chem. 2013 May 6. [Epub ahead of print]

**** Beloosesky R. et al. Prophylactic maternal N-acetylcysteine in rats prevents maternal inflammation-induced offspring cerebral injury shown on magnetic resonance imaging. Am J Obstet Gynecol. 2013 Mar;208(3):213.e1-6. doi: 10.1016/j.ajog.2013.01.023.

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Ghanizadeh A, & Derakhshan N (2012). N-acetylcysteine for treatment of autism, a case report. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 17 (10), 985-7 PMID: 23826003