Oral vitamin D and the inflammatory effects of sunburn

In something of a departure from the typical content of this blog, I want to briefly introduce the paper by Jeffrey Scott and colleagues [1] and specifically the findings that: "Compared to placebo, participants receiving vitamin D3 (200,000 IU) demonstrated reduced expression of pro-inflammatory mediators TNF-α... and iNOS... in skin biopsy specimens 48 hours after experimental sunburn."

Based on a small number of participants who either received a high dose of vitamin D - "vitamin D3 (cholecalciferol)" - or a placebo one hour after experimental sunburn, authors describe how there seemed to be some merit in supplementing with vitamin D (oral dosage form) to help mitigate some of the more damaging, inflammatory effects of sunburn based on their observations. They further noted: "increased skin expression of the anti-inflammatory mediator arginase-1, and a sustained reduction in skin redness, correlating with significant expression of genes related to skin barrier repair" in their supplemented group.

It is perhaps timely that this research is discussed today given the current heatwave that has settled over most of Blighty. If like me, you are sometimes prone to the odd bout of sunburn (8 hours at Flamingo Land has quite a lot to answer for!) such findings could eventually prove to be quite useful. Obviously there is the strong advice not to get sunburn in the first place but added to the various creams and lotions to soothe the skin after sunburn, the possibility that vitamin D supplementation might also come in handy is worthwhile experimentally investigating further. The fact that vitamin D is produced in the skin (albeit in a quite complicated series of biological processes) suggests that Mother Nature knew what she was doing when it came to skin exposure to (excess) sunlight.

On one last point - that related to "the immunotherapeutic properties of vitamin D" - I'd also like to think that other areas of science and medicine could benefit from further research in this area. I've discussed research before on this blog talking about how vitamin D supplementation might be important to certain labels under certain conditions with an immune system/inflammatory component attached to them (see here). Assuming that what goes on in the skin under inflammatory conditions following sunburn is not necessarily a hundred million miles away from what happens to other parts of the body under similar inflammatory conditions, there is perhaps quite a bit we can learn from the sunshine vitamin/hormone and it's multi-faceted effects...

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[1] Scott JF. et al. Oral vitamin D rapidly attenuates inflammation from sunburn: an interventional study. J Invest Dermatol. 2017 May 30. pii: S0022-202X(17)31558-0.

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Vitamin D and depression / depressive symptoms

I promise you that I'm not getting too obsessed with the sunshine vitamin/hormone that is vitamin D despite chatter about it appearing with growing frequency on this blog. It's just that nearly every day now one or more of my research alerts seems to turn up some new study suggesting that we really should be looking at vitamin D with greater assiduity with regards to a whole range of issues. By saying that I would also reiterate the timeless classic: correlation does not equal causation just in case you think I'm overstating any connection.

Journeys @ Wikipedia  

With my autism research blogging hat on, my recent discussions on vitamin D talked about how autism is by no means protective against vitamin D deficiency and indeed, how it might tie into quite a few other areas of research interest around the spectrum. In that post I also talked about how some of the comorbidity which can, and does, seem to appear with greater frequency in autism might also complicate matters when it comes the sunshine vitamin, and in particular the presence of conditions like ADHD (attention-deficit hyperactivity disorder) (see here) and even something like depression [1] which may have some connection to vitamin D levels.

Today I'd like to talk about some more of that cumulative work on vitamin D and depression or depressive symptoms building on the very thorough review and meta-analysis by Anglin and colleagues [1] who concluded: "Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal".

OK, before we start it's probably worthwhile my providing you with some explanation about depression, what is and what it isn't. The Royal College of Psychiatrists has probably one of the best explanations (see here) and how depression goes far beyond just feeling a little bit low for a few days. Most people probably understand that there are various different types of depression which come about for all manner of reasons bridging social, biological and genetic domains. So we're probably talking about a tapestry of different presentations also potentially with some 'common ground' in relation to other behaviourally-defined conditions. With the increasing discussions about how the contents of our second brain might also impact on things like mood [2] I'd also bring you back to some interesting work on various bacteria also being potentially implicated in something like depression too (see here).

So let the cherry-picking commence:

• The paper by Shaffer and colleagues [3] represents yet another review and meta-analysis on depression and vitamin D. They concluded that: "Vitamin D supplementation may be effective for reducing depressive symptoms in patients with clinically significant depression; however, further high-quality research is needed". I should emphasize that term 'clinically significant depression' as being an important part of their findings given that the evidence does not yet seem to indicate that vitamin D is any sort of general purpose mood enhancer. There are far better ways to do this apparently [4].
• Just before however you get too carried away with some effect from vitamin D I should perhaps introduce the paper by Li and colleagues [5] (their protocol is available here) who looking at adult depression concluded: "There is insufficient evidence to support the efficacy of Vit D supplementation in depression symptoms, and more RCTs using depressed patients are warranted".
• Another paper, another systematic review and meta-analysis as per the results from Ju and colleagues [6]. Their conclusions: "an inverse association between serum 25(OH)D levels and the risk of depression. Further studies are warranted to establish whether this association is causal".
• The paper by Black and colleagues [7] offers an interesting perspective on one reason why vitamin D does not seem to offer any unanimous effect on depression across the board. Their analysis based on the Raine cohort (see here) reported: "an association between serum 25(OH)D [vitamin D] concentrations and symptoms of depression, but not anxiety and stress, in males". Gender or sex, is increasingly being seen as an important variable for all manner of health related effects outside of just concepts like the fragile male (see here) as per other findings in the vitamin D-depression research arena [8]. That also age might be an important issue too [9] is worth mentioning.
• Finally, and with the Raine study again in mind, I'd like to bring to your attention the paper by Robinson and colleagues [10] who, after looking at maternal serum vitamin D levels and the instance of post-natal depressive symptoms suggested: "Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms".

I've certainly not been able to do justice to all the peer-reviewed literature out there looking at depression and vitamin D in this post, so please don't take my word as Gospel. I note also that various other relevant areas have been examined in this debate including the issue of sun exposure (outside of vitamin D production) and those all-important vitamin D receptors as a consequence of the disparity between having low levels of vitamin D being linked to depression but supplementation seemingly not necessarily producing a consistent anti-depressant effect [11].

Whilst the evidence is fairly strong for some sort of connection between vitamin D levels and depression, I think most people would be prepared for the fact that the link is likely to be quite complicated. Thinking back to a post I wrote about vitamin D and intestinal permeability (bear with me on this one...) I stumbled across the paper by Vassallo & Camargo [12] talking about a "multiple-hit model" where vitamin D deficiency is involved in a whole cascade of processes linked to the gastrointestinal tract and those trillions of passengers we all carry there. Granted, there's still a lot more science to be done in this area, but as per the review paper by Uwe Gröber and colleagues [13] one should be moving away from vitamin D deficiency just acting and impacting on bone health...

And just as I publish this post, yet another meta-analysis to throw into the melting pot from Spedding [14]... Thick and fast people, thick and fast people...

Music to close. A bit of a classic from the 80s: Belinda Carlisle and Heaven is a Place on Earth.

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

[2] Farmer AD. et al. It's a Gut Feeling - how the gut microbiota affects the state of mind. J Physiol. 2014 Mar 24. [Epub ahead of print]

[3] Shaffer JA. et al. Vitamin D Supplementation for Depressive Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Psychosom Med. 2014 Mar 14. [Epub ahead of print]

[4] Guszkowska M. Effects of exercise on anxiety, depression and mood. Psychiatr Pol. 2004 Jul-Aug;38(4):611-20.

[5] Li G. et al. Efficacy of vitamin D supplementation in depression in adults: a systematic review. J Clin Endocrinol Metab. 2013 Dec 10:jc20133450.

[6] Ju SY. et al. Serum 25-hydroxyvitamin D levels and the risk of depression: a systematic review and meta-analysis. J Nutr Health Aging. 2013;17(5):447-55.

[7] Black LJ. et al. Low vitamin D levels are associated with symptoms of depression in young adult males. Aust N Z J Psychiatry. 2013 Nov 13. [Epub ahead of print]

[8] Kwasky AN. & Groh CJ. Vitamin D and depression: is there a relationship in young women? J Am Psychiatr Nurses Assoc. 2012 Jul-Aug;18(4):236-43.

[9] Lapid MI. et al. Vitamin D and depression in geriatric primary care patients. Clin Interv Aging. 2013;8:509-14.

[10] Robinson M. et al. Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms. Arch Womens Ment Health. 2014 Mar 25. [Epub ahead of print]

[11] Kjærgaard M. et al. Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry. 2012 Nov;201(5):360-8.

[12] Vassallo MF. Camargo CA Jr. Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children. J Allergy Clin Immunol. 2010 Aug;126(2):217-22.

[13] Gröber U. et al. Vitamin D: Update 2013. From rickets prophylaxis to general preventive healthcare. Dermato-endocrinology 2013; 5:3, e2.

[14] Spedding S. Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws. Nutrients. 2014 Apr 11;6(4):1501-18.

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Anglin RE, Samaan Z, Walter SD, & McDonald SD (2013). Vitamin D deficiency and depression in adults: systematic review and meta-analysis. The British journal of psychiatry : the journal of mental science, 202, 100-7 PMID: 23377209

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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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

Waiting patent-ly: Gc globulin, vitamin D and autism?

As summer inevitably turns to Autumn and the prospect of those colder, darker winter days and nights further encroaches, I find myself again talking about the growing body of research and speculation suggestive of a link between autism (or at least some of the autisms) and the sunshine vitamin - vitamin D - and its related biochemistry.

Autumn @ Wikipedia 

I was brought to this post by an interesting patent application by The Trustees Of Columbia University In The City Of New York regarding an invention by two very well known and renowned scientists: Ian Lipkin and Mady Hornig titled: "Autism-associated biomarkers and uses thereof" (see here*).

Filed earlier this year (2013) the application discusses quite a few things with a focus on vitamin D and autism and in particular: "detecting whether or not there is an alteration in the express of a Gc globulin protein in the subject as compared to a non-autistic subject".

OK, some background just in case you need it. Vitamin D is something of a rock star in health research circles of late. Traditionally thought to be just the stuff needed to help the absorption of calcium, a more varied role has been reported for the sunshine vitamin in recent years covering lots and lots of ailments and conditions. With autism in mind, vitamin D has been the source of quite a bit of speculation** and research (see my previous posts here and here and here). Although requiring further investigation, it would be a brave/foolish (delete as appropriate) person to say that it shows absolutely no link to autism or at least certain facets or cases of autism on the basis of the existing evidence.

Researchers, Ian Lipkin and Mady Hornig, are also highly respected on this blog. Regular readers might remember their names in relation to quite a few topics I've talked about including the old XMRV-CFS/ME de-discovery story (see here) and the fascinating work on autism and Sutterella (see here). Prof Lipkin was also credited in bringing 'science to Hollywood' in his role as an adviser for the film Contagion (see here) and they both share credit for the 'three strikes hypothesis'. Indeed, this is not the first time that their autism work has entered the patent arena (see here).

The recent patent application, I have to admit, was hard going for me in terms of all the details it contained. My trawl for some background information on Gc globulin protein - also I think called vitamin D binding protein (DBP) - revealed that this protein is principally involved in getting vitamin D and its relations around the body among other things***. Specifically the patent is built on: "the finding that increased levels in the Gc globulin GcFl (which is a vitamin D binding protein) can serve as a biomarker for human Autism Spectrum Disorders". This I interpret to mean that too much Gc globulin being present means that too much vitamin D gets bound up with the stuff and levels of free, available vitamin D (and metabolites) might therefore be lower than that required. The patent goes on: "elevated levels of Gc globulin in the umbilical cord plasma of ASD patients were observed relative to control cases".

These are potentially big words. At the time of writing (September 2013) I was unable to find anything in the peer-reviewed research literature looking at Gc globulin in relation to autism, let alone anything suggesting that increased levels of the protein might be the stuff of biomarkers. That's not to say that there may not be something waiting in the pre-publication arena about this, as per the patent talking about proteomic analysis of "umbilical cord blood plasma samples from children diagnosed with autism (n=l 1 cases) and children without evidence of developmental disorder (n=12 controls)". Proteomics you say?

Further down the patent I noted other points. So: "administering to the subject a therapeutic amount of GcMAF, thereby treating or preventing autism or an ASD". Without getting into any debates about treatment and prevention (which seems to be a common theme as per the MAR autism letter recently), Gc-MAF is another interesting part of this application. Regular readers might have seen my post on Gc-MAF and nagalase in relation to autism (see here) and the early-day connections being made there (see here also).

A quick non-expert look at the connection between Gc globulin and Gc-MAF reveals that Gc globulin is the precursor to Gc-MAF****. I think (and it is just that) the patent is suggesting that because greater than usual quantities of vitamin D might be bound up with Gc globulin, there are knock-on immune effects resulting from this vitamin D deficiency, ergo: "administering to the subject a therapeutic amount of GcMAF, thereby treating or preventing the vitamin D deficiency-related immune deficit." Onwards, the assumption is that this might have an effect on the presentation of autism too. Again, with my non-expert hat on, administration of Gc-MAF does seem to affect Gc globulin activity (at least in the lab and using cells from patients with systemic lupus erythematosus*****). Don't quote me on that by the way.

There is quite a bit more information included in this patent which I can't cover here in one post. As if you needed more evidence that vitamin D deficiency might be quite prevalent in autism (and across different geographies) I would also refer you to the recent papers by Duan and colleagues****** & Gong and colleagues******* based in China. That being said, if the Lipkin/Hornig patent turns out to be correct at least for some on the autism spectrum, simply adding more vitamin D into the diet or supplementing or increasing sunshine exposure when a deficiency is present alongside high levels of Gc globulin, might not necessarily be the most desirable course of action.

Finally, I should point out that this is a patent application and not peer-reviewed science so whilst being as enthused as I am about the potential for this line of inquiry, one has to take a step back. As with all patent applications, the aim is protection; protection for the your work, the intellectual property of your work and indeed, the commercialisation of your work from being copied by others presumably for profit. Autism has seen its fair share of patents down the years, over 98,000 at the time I looked, and whilst many would love to see these patents actually produce some real-life benefits for people with autism and their families, the question is: how many actually do?

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* Autism-associated biomarkers and uses thereof. The Trustees Of Columbia University In The City Of New York. WO2013130953 A2. Application number PCT/US2013/028589. Filed: March 1 2013. Published: September 6 2013.

** Cannell JJ. Autism, will vitamin D treat core symptoms? Med Hypotheses. 2013 Aug;81(2):195-8. doi: 10.1016/j.mehy.2013.05.004.

*** Haddad JG. Plasma vitamin D-binding protein (Gc-globulin): Multiple tasks. J Steroid Biochem Mol Biol. 1995; 53: 579-582.

**** Nagasawa H. et al. Gc Protein (Vitamin D-binding Protein): Gc Genotyping and GcMAF Precursor Activity. Anticancer Res. 2005; 25: 3689-3696.

***** Yamamoto N. et al. Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1997 Mar;82(3):290-8.

****** 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.

******* Gong ZL. et al. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport. 2013 Oct 1. [Epub ahead of print]

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Cannell JJ (2013). Autism, will vitamin D treat core symptoms? Medical hypotheses, 81 (2), 195-8 PMID: 23725905

ADHD and a sunny disposition

'Light it up blue' is probably a familiar phrase to many of those involved with autism as being the message championed by Autism Speaks on World Autism Awareness Day (2 April). The intention is noble enough: to bring autism to the attention of the world at large and importantly, keep their attention and resources focused on autism. I might add that awareness is one thing; actually 'doing something about autism' - whether that means improving prospects or modifying the course of autism or just levelling the playing field - is quite another thing.

Light it up @ Wikipedia  

By a funny twist of Internet fate, I stumbled upon a review of the study published by Arns and colleagues* looking at the possibility of a link between solar intensity (SI) and the prevalence of attention-deficit hyperactivity disorder (ADHD). The very tentative light it up blue connection was a sentence or two in the study write-up which suggested that the sleep problems which apparently come with a diagnosis of ADHD might result from "exposure to blue-light during the evening" and that strong sunlight during the day "might reset the biological clock and act as an antidote to the evening exposure to artificial blue-light causing sleep onset problems". Yes, I know it isn't a great blue light pun, sorry about that.

It should be noted that the Arns paper appears in a pretty good journal (Biological Psychiatry) so whilst you might be thinking, 'solar intensity... eh?' this is a correlation which has passed what one would expect to have been quite a rigorous peer-review battlefield. I could at this point offer you some more detailed description of the paper but it seems that the authors have already done that on their website (see here - no endorsement given or intended).

In effect, they mapped the prevalence figures for ADHD across various parts of the US and beyond and cross-referenced them with official figures relating to SI. Yes, prevalence of ADHD were partly based on "self-report of professional diagnoses" but this was to some degree countered by the use of more formal assessment data in other sites. They found a correlation (negative correlation) between ADHD prevalence and SI when controlling for various potential confounders: "a lower prevalence of ADHD in areas with high SI for both U.S. and non-U.S. data".

Bearing in mind the issue of correlation/causation (see here), one could construe this data several ways. If for example you work for the tourist boards of Arizona, Nevada or California you have a potentially interesting advert: 'Come live here, we've got lots of solar resource and potentially less risk of your children developing ADHD'. Or words to that effect. And indeed, the CDC figures do seem to suggest that those high SI states might have a lower prevalence of ADHD (assuming that this doesn't reflect other issues such as awareness, identification, etc). On a more serious note are the suggestions that (a) ADHD might be related to circadian clock disturbances, and (b) that exposure to the various new-fangled technologies we are surrounded by might be part and parcel of those circadian clock disturbances.

Just before you reach for the click away button, like I almost did, mumbling 'blame it all on technology', there are a few papers to bring to your attention. Yes, sleep issues are associated with ADHD** and indeed if the recent paper from Blesch and Breese McCoy*** is anything to go by, we might also assume that ADHD - some cases of ADHD - could be mistaken for things like sleep apnoea. True also that issues with circadian function seem also to be tied into cases of ADHD as per studies like this one from Gamble and colleagues****. On balance, sleep seems to show some connection with ADHD.

That the part of the light spectrum labelled blue emanating from various technology use is the primary cause or significant contributor to the sleep issues noted even in some cases of ADHD is the slightly more difficult proposition for me to whole-heartedly (hoof hearted!) accept from this work. I don't doubt that many children and adults with ADHD use this kind of technology. But I have to ask whether their use and exposure to the artificial blue light is really any more significant than that of everyone else? Indeed, without being an expert on the different ranges or wavelengths of light and their physiological effects, are we just talking blue or are we talking other parts of the light spectrum too?

There are details from this study which I would like to see further explored given the potential for a relationship between SI and ADHD prevalence. Readers for example, might know that I am more than a little intrigued by another sun related variable, vitamin D, and its various connections (or not) to conditions like autism or chronic fatigue syndrome among others. The question would have to be whether the sunshine vitamin / steroid hormone might also show some relationship to the latest findings? Are vitamin D levels likely to be greater / the same / reduced in cases of ADHD dependent on the specific geography and SI? Vitamin D receptors all in good working order*****? No significant drug interactions where medication is being used? Indeed, whether other correlates such as altitude - which also seem to map onto the SI exposure plots - might come into play?

There are questions which require some follow-up from this work but for now, and with all caveats in good working order when it comes to population studies of association - as with other recent results too, I'm intrigued by the Arns data and the suggested overlap. And also that ADHD might not be the only condition being looked at with a sun-related variable (see this study by Davis & Lowell******, full-text).

To close, after recently watching the quite brilliant film 'Rock of Ages' which satisfied all my 1980s rock needs, a taste of Sheffield's finest.

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* Arns M. et al. Geographic Variation in the Prevalence of Attention-Deficit/Hyperactivity Disorder: The Sunny Perspective. Biol Psychiatry. March 2013.

** Yürümez E. & Kiliç BG. Relationship Between Sleep Problems and Quality of Life in Children With ADHD. J Atten Disord. March 2013.

*** Blesch L. & Breese McCoy SJ. Obstructive Sleep Apnea Mimics Attention Deficit Disorder. J Atten Disord. March 2013.

**** Gamble KL. et al. Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study. Chronobiol Int. February 2013.

***** Malik S. et al. Common variants of the vitamin D binding protein gene and adverse health outcomes. Crit Rev Clin Lab Sci. 2013; 50: 1-22.

****** Davis GE. & Lowell WE. Variation in ultraviolet radiation and diabetes: evidence of an epigenetic effect that modulates diabetics' lifespan. Clinical Epigenetics. 2013; 5: 5.

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Arns M, van der Heijden KB, Arnold LE, & Kenemans JL (2013). Geographic Variation in the Prevalence of Attention-Deficit/Hyperactivity Disorder: The Sunny Perspective. Biological psychiatry PMID: 23523340

Autism and migration: new clues?

Autism in the Somali population, particularly the migrating Somali population, has been the topic of some debate down the years. I think back to the 2010 study by Barnevik-Olsson and colleagues* detailing an autism prevalence in Somalis living in Sweden of 0.98% compared with 0.21% in children of non-Somali origin alongside other factors related to vitamin D for example. OK, the vitamin D link is still speculative but the migratory aspect remains an interesting association. Enter a new study into the debate from Magnusson and colleagues** detailing some population based findings relating to parental migration status and risk of autism spectrum condition.

The summary:

• Based on an analysis of various records for the total child population of Stockholm County, Sweden (N=589,114) between 2001 and 2007, children with autism defined as high- and low-functioning were identified. I know some people don't like the terms 'high' and 'low' functioning as descriptors of autism, but in this case the authors were referring to cases where intellectual disability was or was not present.
• A total of 4952 cases of autism were identified; 2097 cases comorbid with learning disability (42%) and 2855 cases of autism without (58%). These splits are roughly in line with other data such as that reviewed by O'Brien and Pearson***.  
• When looking at children of migrant parents, there was an increased risk of having a child with autism and learning disability (OR = 1.5) and this risk was particularly pronounced for those migrating from countries with a low human development index and for children whose mothers migrated just before or during pregnancy (OR = 2.3).
• When it came to risk of having a child with autism without intellectual disability, there was actually a decreased risk for migrant mothers compared to children born to indigenous mothers. Whether this was a true reflection of risk or due to the fact that immigrant families might be less likely to seek child development services is unknown.
• These results were not explained by socio-economic, age or obstetric factors.

There are quite a few potentially important implications from this work which require comment.

Over 40% of cases of autism identified in this study were diagnoses of autism and learning disability. One of the blogs I like to follow is Harold Doherty's blog. Some of his more recent discussions have surrounded what will happen to those cases of autism and learning disability in the proposed revisions to the DSM criteria for autism. With the current figures in mind, the question has to be asked whether this kind of relationship will be picked up in any future studies if and when the new guidance is enshrined in diagnostic law.

One also needs to comment on the environmental implications from this latest study. The fact that risk of offspring with autism was elevated just before or during pregnancy implies that genes alone cannot guide this association. I say cannot guide this association but possibly they could if one was to assume that some epigenetic relationship may be evident. I think again back to the prenatal vits and SNPs study on autism from last year. So, assuming that mum is migrating from a warm, sunny environment to a cold, not so sunny (at least not with as strong a sun) environment, where the food may be different, the external environment different (including the 'chemical' environment) and the associated 'stress' that comes with moving to a different part of the world. Mmm.. seems to me that there are plenty of factors ripe for further study there.

Ultimately this is another study of population association and one has to bear in mind the limitations in terms of what information that can bring. Having said that, on top of the other immigrant studies undertaken on autism, there is a growing argument that more focused investigation might yield some interesting clues as to risk and potentially aetiology at least in some cases of autism.

* Barnevik-Olsson M. et al. Prevalence of autism in children of Somali origin living in Stockholm: brief report of an at-risk population. Developmental Medicine & Child Neurology. 2010; 52: 1167-1168

** Magnusson C. et al. Migration and autism-spectrum disorder: population-based study. British Journal of Psychiatry. February 2012.
DOI: 10.1192/bjp.bp.111.095125

*** O'Brien G. & Pearson J. Autism and learning disability. Autism. 2004; 8: 125-140.
DOI: 10.1177/1362361304042718

You are my sunshine: vitamin D and autism

Historically, England and Scotland have perhaps not enjoyed the best of relationships. Anyone who has watched the blood and guts of the film Braveheart, very, very, very loosely based on the life and times of Sir William Wallace, will get an idea of what the main problems were in terms of conquest, lands, identity and freedom. Down the years some degree of one-upmanship still survives as evidenced by little things like the 'anyone but England' slogan during the recent World Cup. Those who watched the 2010 World Cup will know that the English football (soccer) team did pretty well on their own in early-exiting the tournament without the help of the ABE campaign.

As an Englishman living fairly close to the Borders, I don't want to get too involved in the politics. My geographical proximity to Scotland does however give me a little bit of a flavour of the climate in Scotland and its relevance to this post on vitamin D.

I was intrigued by a comment made to me quite recently when discussing measuring levels of vitamin D. The comment included the term 'normal for Scotland' when interpreting some biochemical results on vitamin D levels in various patient groups. I found out that day that 'normal for Scotland' is usually taken to mean vitamin D results are not abnormal when compared to the Scottish population but neither do they show a particularly healthy level of vitamin D to be present assuming accuracy of the testing procedure. One of the possible reasons: well whilst the sun does shine in Scotland (sometimes), there is quite a bit of evidence to suggest that it doesn't necessarily translate into an all-year round adequate vitamin D level for many, many people living at certain geographical coordinates all of which cover Scotland; indeed also where I live.

I should perhaps back-up a little and provide a little more description of vitamin D first. Vitamin D is a fat-soluble vitamin. Although having multiple uses throughout the body, vitamin D is perhaps most famous for its role in aiding in the absorption of calcium; see my recent post on this subject. There are a few ways of getting vitamin D; through our modern fortified diet (assuming you eat breakfast cereals for example) and also by contact with sunshine, or more specifically via exposure to ultraviolet B light. I suppose a third way is via supplementation.

Vitamin D is a vitamin in the spotlight at the moment. There is quite a lot of research coming out telling us how much we need vitamin D for lots of different health reasons, ranging from cancer prevention to maintaining good cognitive health to potentially helping to tackle growing health problems like diabetes. Looking at childhood health in particular, there is some pretty good evidence that conditions classically associated with vitamin D like rickets might be making an unwelcome return here in the UK and beyond. Although not altogether clear as to what is driving our vitamin D deficiency, it seems as though lifestyle is a possible factor; so sitting reading blogs from a home PC indoors rather than reading them on an iPad outdoors, our use of barrier creams to prevent excessive sun exposure and its onward effects, but also physiological factors such as skin colour (although research in this area is not cut and dried).

There is also some suggestion that vitamin D might show some connection to various childhood developmental conditions including autism. Vitamin D and psychiatry have, what might be called, a blossoming relationship. PubMed lists over 100 entries based on the keywords vitamin D and schizophrenia, covering various angles of a possible connection from genes to biochemistry, even including psychology. I would not be so bold as to say that the link is in anyway definitive, but it makes for some interesting reading.

With autism in mind, vitamin D has also received more than passing mention. As with all dietary components, the possible influence of unusual eating habits and patterns attributed to many cases of autism, would perhaps predispose some people on the autism spectrum to a reduced intake of dietary-derived vitamin D. The research in this area does seem to corroborate this suggestion. One of the bigger names in all things vitamin D, Dr John Cannell, wrote an interesting paper about vitamin D and autism not so long ago (here). Putting the universality of the vitamin D-autism hypothesis to one side, there are some interesting points raised in his paper which are beginning to be borne out by the accumulated research in this area. In particular are the various research on autism in specific ethnic populations such as the Somali community, and the evidence put forward for some increase in autism prevalence in such groups when resident in more Northern climes. I would reiterate the old 'correlation does not imply causation' adage at this point also.

Another interesting area of research relates to the various work on the gastrointestinal (GI) co-morbidities noted alongside some cases of autism, and whether malabsorption as a result of coeliac disease or hyperpermeability of the gut might play a hand in hypovitaminosis D as has been suggested elsewhere. This research published on Egyptian children might be relevant to this side of the hypothesis given that I am sure that sunshine is at a premium in the land of the Pharaohs. Finally, although there is no contemporary epidemiological evidence to speak of, autism does not seem to be protective against the development of rickets as witnessed by this study (one of the study authors being also involved in this paper on iron deficiency and autism) and this study.

Taking into account the evidence currently available, I don't think that we can say that autism, or any one condition, has a monopoly on low levels of vitamin D. Many people from many different ethnic, geographic and symptomatic groups seem to be on the low side of what would be considered to be 'adequate' levels of vitamin D. There is also the 'chicken and egg' situation in terms of whether vitamin D levels are 'causative' of anything (outside of rickets or other classically related conditions) as complicated as autism or schizophrenia, etc. or just symptomatic of some other underlying mechanism or dysfunction. I will leave you to make your decision on this issue. Finally, vitamin D might be only one part of any association as can be seen by this editorial on how UVB sunlight might also have some other interesting effects.

To finish, this Sassenach wonders how many miles would you walk?