Thursday, 17 April 2014

Mitochondrial dysfunction as a neurobiological subtype of autism

The paper by Suzanne Goh and colleagues [1] reporting on "a possible neurobiological subtype of mitochondrial dysfunction in ASD [autism spectrum disorder]" is a worthy addition to the research roll call which has graced this blog down the years. Based on the analysis of brain lactate levels - a potential marker of mitochondrial dysfunction - via the analysis of lactate doublets on brain magnetic resonance spectroscopic imaging (MRSI), authors picked up a significantly higher rate of lactate in cases of autism spectrum disorder (ASD) when compared to age and sex-matched asymptomatic controls. I've talked lactate and autism before on this blog (see here) so very much welcomed this research looking specifically at brain levels of this stuff.

I'm writing this post having already scheduled a blog entry on the recent paper by Rose and colleagues [2] (open-access here) on the increasing complexity of mitochondrial dysfunction being seemingly present in some cases of autism. Given the findings from Goh et al I've decided to publish this entry first (just to confuse everyone even further) as yet again, my confusion on the topic of all-things mitochondrial has an opportunity to shine through.

So then, a few details from the Goh paper:

  • Based on imaging and other data derived from 75 participants diagnosed with an ASD (aged 5-60 years) contrasted with 96 typically-developing controls, the authors set about "assessing in-vivo evidence of mitochondrial dysfunction directly in the brains of a large sample of children and adults with ASD".
  • Whilst not an imaging man, I can tell you that they used proton multiplanar spectroscopic imaging (MPSI) to quantify endogenous brain chemistry and "regional cellular metabolism and function" specifically towards the detection of lactate. Actually, the talk of [lactate] doublets is not a million miles away from the results one gets as a consequence of a related chemical analytical technique, NMR, which brings back memories of some work from days gone by.
  • After laying down quite a few ground rules for what was and wasn't a readable result, the authors concluded that: "Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than in typically developing controls (1%) (P = .001), providing in vivo evidence for the presence of mitochondrial dysfunction in the brains of individuals with ASD". In-vivo by the way, means in the living and contrasts with science done in a test-tube (in-vitro).
  • Age was a factor when it came to lactate levels, with elevations reported more often in adults than in children. This phenomenon has been talked about before in the research literature [3].
  • The authors go on to discuss the implications of their results. Bearing in mind the various situations where elevated brain lactate levels have been noted outside of just ageing, including as a result of issues like anxiety or panic disorder [4], they reiterate how their "strict exclusion critera and careful scanning procedures made such explanations less likely". Further they highlight how: "individuals with ASD should undergo evaluation for mitochondrial dysfunction, as novel and promising treatments are under development for mitochondrial disorders".

As per my link above, this is not the first time that lactate has appeared in the autism research literature. I'll for example, draw your attention to the paper by Al-Mosalem and colleagues [4] and their reporting that: "Lactate as an important energy metabolite for the brain was significantly higher in autistic patients compared to control showing about 40% increase". Bear in mind however that this and other results [5] have tended to look in plasma rather than directly what's going on in the brain as Goh et al did.

There's little more for me to say on this area of research aside from the need for further replicative investigations and perhaps a little more inquiry into the subgroup of people with autism who fall into this mitochondrial dysfunction category bearing in mind the continued focus on the plurality of autism (the autisms). That there may be interventions available for mitochondrial disorder when present [6] is another important point. As per related research in other conditions with a potential mitochondrial aspect to them (see here), at least one of the interventions - Coenzyme Q10 (ubiquinol) - is being looked at with some autism in mind [7] (open-access here) bearing in mind no medical or clinical advice is given or intended.

Music then to close. I'm thinkin' of something with a candy orientation given the time of year, so again, ladies and gentlemen, Mr Sammy Davis Jnr and The Candy Man.. (he can you know).


[1] Goh S. et al. Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder. Evidence From Brain Imaging. JAMA Psychiatry. 2014. April 9.

[2] Rose S. et al. Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines. Transl Psychiatry. 2014 Apr 1;4:e377.

[3] Ross JM. et al. High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio. PNAS. 2010; 10.1073/pnas.1008189107

[4] Al-Mosalem OA. et al. Metabolic biomarkers related to energy metabolism in Saudi autistic children. Clin Biochem. 2009 Jul;42(10-11):949-57.

[5] Oliveira G. et al. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol. 2005 Mar;47(3):185-9.

[6] Parikh S. et al. A Modern Approach to the Treatment of Mitochondrial Disease. Curr Treat Options Neurol. Nov 2009; 11(6): 414–430.

[7] Gvozdjáková A. et al. Ubiquinol improves symptoms in children with autism. Oxid Med Cell Longev. 2014;2014:798957.

---------- Goh, S., Dong, Z., Zhang, Y., DiMauro, S., & Peterson, B. (2014). Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2014.179