Monday, 15 September 2014

Zinc and copper and autism

The paper by Li and colleagues [1] looking at serum copper (Cu) and zinc (Zn) levels in a group of participants diagnosed with an autism spectrum disorder (ASD) is the source material for today's post. Highlighting how "mean serum Zn levels and Zn/Cu ratio were significantly lower in children with ASD compared with normal cases... whereas serum Cu levels were significantly higher" the continued focus on the metallome in autism carries on at a pace. I should at this point out that I'm not in favour of the use of the word 'normal' in this or any context (anyone who feels that they are normal, please make themselves known to the population at large).

"Bring me... the bore worms!"
Anyhow... I've talked zinc and autism / other conditions on this blog quite a few times (see here and see here). Alongside other more recent data [2] there is a growing realisation that zinc deficiency present in at least some diagnosed on the autism spectrum might have quite a few implications. With this thought in mind, I might also draw your attention to the recent paper by Chaves-Kirsten and colleagues [3] talking about how zinc might also show some connection to the protein kinase of the hour, mTOR (see here) and in particular reducing mTOR levels in a rodent model of autism. This follows other work in this area [4].

The Li paper alongside looking at individual levels of zinc and copper and how they seemed to correlate with presented symptoms according to the Childhood Autism Rating Scale (CARS) also talks about the zinc/copper ratio which is something that has been previously discussed in the peer-reviewed literature with reference to autism and various other conditions as per the excellent review by Osredkar & Sustar [5] (open-access). The paper by Faber and colleagues [6] for example, indicated that a low Zn/Cu ratio may "indicate decrement in metallothionein system functioning". They also talked about how issues with this ratio "may be a biomarker of heavy metal, particularly mercury, toxicity in children with ASDs" as per the various biological uses of metallothionein [7]. I know this moves discussions into some quite uncomfortable realms but science is science (see here) and one should not be afraid to have scientific discourse on any topic. Importantly too, the Faber results also seemed to show more than a passing similarity to those presented by Li et al. Same goes for the paper by Russo and colleagues [8].

The other interesting point recorded by Li and colleagues was their use of the good 'ole ROC curve as a means to indicate an "auxiliary diagnosis of autism". More frequently linked to a certain Egyptian-Saudi autism research group (see here), ROC curves - "a fundamental tool for diagnostic test evaluation" - basically plots the true positive rate against the false positive rate for a test. Li et al projected the cut-off value for the Zn/Cu ratio to be 0.665 for a diagnosis, with "a sensitivity of 90.0% and a specificity of 91.7%". Bearing in mind the relatively small participants included for analysis (n=60), those aren't bad figures for sensitivity and specificity remembering my recent discussions on the observation-based classifier (OBC) from Wall and colleagues [9] (see here) and what they got.

There's little more for me to say about the Li data that I haven't already said here and in other posts on this topic. If you want to read a little more about the possible role of zinc and copper in cases of autism, the report by Bjorklund [10] covers quite a bit of the literature on possible links. The next question is what might we be able to do about any issues in this area? [11]

So then, The Last of the Famous International Playboys? (not me of course..)

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[1] Li SO. et al. Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport. 2014 Aug 26.

[2] Grabrucker S. et al. Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain. 2014 Jan;137(Pt 1):137-52.

[3] Chaves-Kirsten GP. et al. Prenatal zinc prevents mTOR disturbance in a rat model of autism induced by prenatal lipopolysaccharide. Brain, Behavior & Immunity. 2014; 40: e11-e12.

[4] McClung JP. et al. Effect of supplemental dietary zinc on the mTOR signaling pathway in skeletal muscle from post-absorptive mice. FASEB J. 2006; 20 (Meeting Abstract Supplement) A627.

[5] Osredkar J. & Sustar N. Copper and Zinc, Biological Role and Significance of Copper/Zinc
Imbalance. Journal of Clinical Toxicology. 2011; S3.

[6] Faber S. et al. The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers. 2009 May;14(3):171-80.

[7] Coyle P. et al. Metallothionein: the multipurpose protein. Cell Mol Life Sci. 2002 Apr;59(4):627-47.

[8] Russo AJ. et al. Plasma copper and zinc concentration in individuals with autism correlate with selected symptom severity. Nutr Metab Insights. 2012 Feb 28;5:41-7.

[9] Duda M. et al. Testing the accuracy of an observation-based classifier for rapid detection of autism risk. Transl Psychiatry. 2014 Aug 12;4:e424.

[10] Bjorklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp (Wars). 2013;73(2):225-36.

[11] Russo AJ. & Devito R. Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger's Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism. Biomark Insights. 2011;6:127-33.

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ResearchBlogging.org Li SO, Wang JL, Bjørklund G, Zhao WN, & Yin CH (2014). Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport PMID: 25162784