Vitamin D and schizophrenia meta-analysed

It's been a few weeks since I last talked about vitamin D on this blog and some finding or other talking about a deficiency of the stuff. Indeed, the last occasion was the publication of the Eva Kočovská study (see here) talking about issues with vitamin D being present across quite a few people on the autism spectrum, continuing a research trend (see here).

So as to remedy this vitamin D blogging deficiency, today I'm talking about the systematic review and meta-analysis by Ghazaleh Valipour and colleagues [1] who concluded: "the overall prevalence of vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4%–84.2%)". They called it a 'strong' association between issues with vitamin D and schizophrenia and add that there is a requirement for quite a bit more research in this area. Some of the accompanying media to this research can be seen here.

A quick look at some of the studies included in the Valipour paper and the wider peer-reviewed evidence on the topic of vitamin D and schizophrenia suggests that there is quite a bit of research history in this area. The paper by McGrath and colleagues [2] (open-access here) quite neatly summarises some of the possible hows and whys of the 'vitamin D hypothesis of schizophrenia' covering variables like "season of birth, place of birth, and migrant status". Some of the same authors have looked at issues such as neonatal vitamin D status and subsequent risk of schizophrenia [3], reporting some intriguing results based on both low and high concentrations "associated with increased risk of schizophrenia". Quite a lot of the research literature has also focused on the psychosis aspect to schizophrenia and how that might fit with the vitamin D aspect. Crews and colleagues [4] for example, reported "higher rates of vitamin D deficiency in people with FEP [first episode psychosis] compared to matched controls". This follows other research hinting at similar findings [5].

The issue of vitamin D supplementation as potentially modifying either risk of schizophrenia or the course of the condition is a slightly more under-researched aspect. Again, McGrath and colleagues [6] have reported results based on retrospective analysis of vitamin D supplementation during infancy impacting on adult risk of schizophrenia, indicating that "either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia". Without any medical or clinical advice given or intended they suggested that "the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses". When it comes to vitamin D as an intervention for current presentation of schizophrenia, the research literature is a little less generous in terms of output.

Reproduced from Gröber et al (2013)

The question of how and why vitamin D might impact on the risk or presentation of schizophrenia is as yet unanswered. The excellent review on all-things vitamin D by Uwe Gröber and colleagues [7] (open-access) offers quite a few possible suggestions why vitamin D might impact on the condition. I've taken the liberty of reproducing a diagram from their paper, so take your pick.

The brain is one of the target organs for vitamin D as for example, discussed by Groves and colleagues [8]. My continuing interest in all-things epigenetic is also served by the paper from Fetahu and colleagues [9] (open-access) talking about vitamin D and epigenome. Immune system effects associated with vitamin D [10] (open-access) also represents a growth area which might be pertinent to cases of schizophrenia particularly when it comes to inflammation or inflammatory responses and something like gastrointestinal inflammation [11] in light of other findings in schizophrenia. The immune system effects of vitamin D might also be regarded more highly in light of the recent news that among the increasing number of genes potentially related to schizophrenia are some "providing support for the speculated link between the immune system and schizophrenia" [12]. I'm sure there are other potentially important variables too.

Anyone who follows the peer-reviewed literature on vitamin D will not doubt have noted a bit of an explosion in interest on the sunshine vitamin/hormone. You name the condition, and someone, somewhere, will probably have investigated the link with vitamin D. Hypertension, check [13]. Cancer mortality, check [14]. Depression, check (see here). ADHD, check (see here). And the list goes on and on, bearing in mind the old adage: correlation is not the same as causation. Given the pervasiveness of vitamin D deficiency and it's potential links to so many different conditions or health issues, it is tempting to think that any correlation is merely coincidental or spurious. Surely this vitamin/hormone could not be acting so widely?

Personally, I'm keeping an open mind about the many and varied links reporting in the scientific literature about vitamin D. The Valipour paper at the very least, suggests that quite a bit more research effort might need to be directed towards vitamin D and schizophrenia; if not universally relevant to the condition, perhaps just to a subgroup or two...

Music. The Lovecats by The Cure.

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[1] Valipour G. et al. Serum Vitamin D Levels in Relation to Schizophrenia: A Systematic Review and Meta-Analysis of Observational Studies. JCEM. 2014. July 22.

[2] McGrath JJ. et al. Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull. 2010 Nov;36(6):1073-8.

[3] McGrath JJ. et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010 Sep;67(9):889-94.

[4] Crews M. et al. Vitamin D deficiency in first episode psychosis: a case-control study. Schizophr Res. 2013 Nov;150(2-3):533-7.

[5] Belvederi Murri M. et al. Vitamin D and psychosis: mini meta-analysis. Schizophr Res. 2013 Oct;150(1):235-9.

[6] McGrath J. et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res. 2004 Apr 1;67(2-3):237-45.

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

[8] Groves NJ. et al. Vitamin d as a neurosteroid affecting the developing and adult brain. Annu Rev Nutr. 2014 Jul 17;34:117-41.

[9] Fetahu IS. et al. Vitamin D and the epigenome. Front Physiol. 2014 Apr 29;5:164.

[10] Prietl B. et al. Vitamin D and immune function. Nutrients. 2013 Jul 5;5(7):2502-21.

[11] Ghaly S. & Lawrance I. The role of vitamin D in gastrointestinal inflammation. Expert Rev Gastroenterol Hepatol. 2014 Jul 22:1-15.

[12] Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014. July 22.

[13] Vimaleswaran KS. et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014 Jun 25. pii: S2213-8587(14)70113-5.

[14] Bjelakovic G. et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014 Jun 23;6:CD007469.

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Valipour G, Saneei P, & Esmaillzadeh A (2014). Serum Vitamin D Levels in Relation to Schizophrenia: A Systematic Review and Meta-Analysis of Observational Studies. The Journal of clinical endocrinology and metabolism PMID: 25050991