Monday 3 March 2014

Vitamin D and autism: a continuing saga

The "sunshine vitamin" that is vitamin D has cropped up quite a few times on this blog for all manner of reasons. The suggestion of a link (whatever that means) between vitamin D and the autism spectrum conditions has received the lion's share of coverage, be that in relation to measured levels of vitamin D (see here and see here) or more speculatively, the possible impact of something like deficiency of vitamin D to symptoms or physiology (see here and see here). I've also not been adverse to talking about the 'D' in relation to other conditions or states either (see here and see here).
Monet at dusk @ Wikipedia

Without trying to do a Linus Pauling on vitamin D [bearing in mind the pendulum potentially swinging partially his way], I am genuinely interested in how this stuff might show some connection to a condition like autism. Further, whether the reports of deficiency (as they invariably tend to show) reflect something important for core symptoms, or are tied into specific comorbidity [1] or are just purely epiphenomenal and reflective of a more widespread population deficiency [2]. A few papers add to my interest in this area, specifically from Dr John Cannell who heads the non-profit Vitamin D Council based in the US. For those of you who have started to use PubMed Commons, Dr Cannell is certainly putting this post-publication review option to very good use.

So, first up is the paper from Grant & Cannell [3] (open-access here) which looked at US autism prevalence estimates for 2010 "with respect to indices of solar UV-B (UVB) doses" according to state. Based on an analysis of prevalence estimates for autism coupled to variables such as ethnicity and geographical latitude, time of year and solar UVB doses, the authors concluded that "autism prevalence among those aged 6–17 y in 2010 was significantly inversely correlated with solar UVB doses". Further, they speculate about the effects of maternal vitamin D deficiency as a potentially important issue when it comes to offspring autism risk. There was some other media interest in these results at the time of publication in 2012.

Obviously I don't need to point out that this was a number-crunching paper which relies on a statistical association so one has to be quite careful of making too much of the findings. Yes, the authors looked at "other possible risk-modifying factors" such as air pollution (see here) and obesity (see here) but one needs always to be cautious when it comes to correlation (as in, not necessarily equalling causation). That also other researchers have downplayed the maternal vitamin D - offspring autism, sorry autistic traits, link (see here) is also important. Me being me though, I'm still interested in the Grant/Cannell findings, particularly when one considers that not-so-long-ago paper which looked at ADHD prevalence and solar intensity and the growing realisation that autism is probably not a stand-alone condition in terms of comorbidity.

Next up, another paper from Cannell & Grant [4] (open-access here) which is a rather more review type paper on the various biological processes which vitamin D is reported to be involved with and how these might link into autism. I'm not going to rehash the paper in its entirety because it is open-access. That being said, there are some familiar themes contained in the review - autoimmunity, mitochondrial issues, etc - which are all potentially important issues to at least some of the autisms. Picking out one detail however, which fell under the heading 'Comorbid Conditions' I was struck by the discussion about adiponectin levels with autism and vitamin D levels in mind. It may be a slightly off-the-wall thought but given mention of this adipokine and my recent interest in elevated leptin levels being reported in a fair few cases of autism I couldn't help but wonder whether there may be further investigations to be had on an effect of vitamin D in relation to leptin elevations [5] with an autism slant.

What I think is worth taking from these papers and the growing scientific interest in vitamin D and autism including that related to the issue of ethnicity and autism (see here) recently illustrated in the Somali-autism initiative, is that there is still much to do in this area of autism research. That vitamin D deficiency does seem to be an issue for some people with autism [6] should already imply that deficiency should be corrected, save any of the more classical problems coming about as a result [7].

Whether the effects of vitamin D extend further into autism and in particular, the presentation of autism or its suggested biological profile (see here for example), is something I'd like to see more on, with the promise of some potential answers already on the research horizon (see here and see here). Oh, and I should also mention the recent papers by Zhang and colleagues [8] and Patrick & Ames [9] too...

Smartphone vitamin D analysis anyone?

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[1] Anglin RE. et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100-7.

[2] Davies JH. et al. Epidemiology of vitamin D deficiency in children presenting to a pediatric orthopaedic service in the UK. J Pediatr Orthop. 2011 Oct-Nov;31(7):798-802.

[3] Grant WB. & Cannell JJ. Autism prevalence in the United States with respect to solar UV-B doses: An ecological study. Dermatoendocrinol. 2013 Jan 1;5(1):159-64.

[4] Cannell JJ. & Grant WB. What is the role of vitamin D in autism? Dermatoendocrinol. 2013 Jan 1;5(1):199-204.

[5] Long J. et al. 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. J Endocrinol. 2013 Jan 18;216(2):265-71.

[6] Duan XY. et al. Relationship between vitamin D and autism spectrum disorder. Zhongguo Dang Dai Er Ke Za Zhi. 2013 Aug;15(8):698-702.

[7] Stewart C. & Latif A. Symptomatic nutritional rickets in a teenager with autistic spectrum disorder. Child Care Health Dev. 2008 Mar;34(2):276-8.

[8] Zhang M. et al. Do children with mental disorders have higher prevalence of hypovitaminosis D? F1000Res. 2013 Jul 17;2:159.

[9] Patrick RP. & Ames BN. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014 Feb 20

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ResearchBlogging.org Grant WB, & Cannell JJ (2013). Autism prevalence in the United States with respect to solar UV-B doses: An ecological study. Dermato-endocrinology, 5 (1), 159-64 PMID: 24494049

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