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