Zinc and depression

"Low dietary zinc intake is associated with a greater incidence of depression in both men and women, as shown in two prospective cohorts".

At the risk of overdoing the whole 'you are what you eat' sentiment, today I'm addressing a portion of the peer-reviewed research literature linking issues with zinc availability to depression. That opening quote by the way, comes from the paper by Khanrin Phungamla Vashum and colleagues [1] who looked at self-reported dietary intake of zinc based on data derived from "the Australian Longitudinal Study on Women׳s Health (women aged 50-61 years) and Hunter Community Study (men and women aged 55-85 years)". I'll come back to that shortly...

Absinthe is the aphrodisiac of the self

As I've mentioned once or twice before on this blog, the description of 'depression' covers quite a lot of diagnostic ground, with all-manner of correlations put forward to try and account for why depression is seemingly so prevalent in modern society. What does seem to be apparent from the voluminous literature is that various factors, at various times and under various situations seem to contribute to depression as a clinical condition with comorbidity also seemingly playing an important hand. In short, it's very, very complicated and very, very individual.

I've tended to talk more about the physiological correlates linked to various types of depression on this blog as per discussions as diverse as gut bacteria (see here) and autoimmune conditions (see here) and upcoming conversations on something like depression and inflammation. This on top of my borderline obsession with all-things vitamin D (see here). It's not that I'm not interested in the psychological or sociological side of things (as per some chatter about overlapping syndromes) but quantifying such factors is rather more difficult than for example, taking a blood sample and looking at the performance of compound X or gene Y. I'd also drop in the fact that quite a bit of the 'causative' research in the area of psychological and/or sociological factors seems to overlook important factors such as resilience too.

Anyhow, aside from the focus on 'self-report' noted in the Vashum study, which is notoriously problematic when it comes to recording eating habits and patterns, there is actually quite a bit of research already published on the topic of zinc and depression.

• The splendidly named Walter Swardfager and colleagues [2] published a very comprehensive review and meta-analysis on the topic of zinc and depression a little while back (covering the peer-reviewed text up to June 2012). Based on data looking at blood zinc levels in over 1500 people with depression compared against 800 asymptomatic controls, they concluded that: "Depression is associated with a lower concentration of zinc in peripheral blood". Indeed, zinc levels were: "approximately -1.85 µmol/L lower in depressed subjects than control subjects".
• Other studies have complemented the Swardfager findings albeit with zinc deficiency present in a more general context in psychiatry. The findings from Grønli and colleagues [3] (open-access) are a good example, whereby researchers reported: "a significant difference in zinc deficiency prevalence between the control group (14.4%) and the patient group (41.0%)" where the patient group consisted of "psychogeriatric patients" who were "compared with the elderly controls". The findings from Maserejian and colleagues [4] (open-access) also suggested some gender effect mediating the zinc-depression link; specifically: "inadequate dietary zinc intake contributes to depressive symptoms in women".
• Insofar as the reasons for zinc deficiency appearing in cases of depression, science is yet to settle on a definitive answer. The paper by Marcin Siwek and colleagues [5] (open-access) suggested three possible reasons: (i) nutritional deficiencies as per the Vashum findings, (ii) "hyperstimulation of the hypothalamic-pituatary-adrenal (HPA) axis, and the associated hypercortisolism" and/or (iii) the result of an inflammatory response "associated with oxidative stress". That last variable on inflammation and oxidative stress might also tie into other data on zinc supplementation "decreasing oxidative stress and generation of inflammatory cytokines such as TNF-alpha and IL-1beta" in certain patient groups [6]. I might also refer you to an excellent post by Dr Emily Deans titled: 'Zinc! An Antidepressant?' with a more detailed analysis of some of the possible hows and whys.
• The supplementation of zinc in cases of depression has also been covered in the research literature. As an adjunctive therapy, Ranjbar and colleagues [7] (open-access) reported that: "zinc supplementation together with SSRIs antidepressant drug improves major depressive disorders more effectively in patients with placebo plus antidepressants (SSRIs)". A review of some of the controlled trials prior to the Ranjbar results by Lai and colleagues [8] concluded similar things with regards to zinc as an 'add-on' treatment but that: "There is less clear evidence on the effectiveness of zinc supplementation alone on depressive symptoms of non-depressed healthy subjects". 
• Animal studies have complemented this collected literature as for example, reported by Tassabehji and colleagues [9] looking at rats; the authors suggested that: "zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment".

There is quite a compelling scientific case for far greater research inspection of zinc in relation to depression and for example, further working out what it seems to be doing. Important too is the issue of who might be the best-responders to something like zinc supplementation in relation to depression/depressive symptoms.

That being said, I wouldn't want anyone to assume that I'm advocating zinc supplementation as some sort of cure-all for depression or anything else. To repeat myself: depression is a very complex set of conditions combining both biology and psychology. Science is still feeling its way around this area, despite the importance of nutrition to depression being increasingly recognised (see here).

So... Cosmic Girl by Jamiroquai.

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[1] Vashum KP. et al. Dietary zinc is associated with a lower incidence of depression: findings from two Australian cohorts. J Affect Disord. 2014 Sep;166:249-57.

[2] Swardfager W. et al. Zinc in depression: a meta-analysis. Biol Psychiatry. 2013 Dec 15;74(12):872-8.

[3] Grønli O. et al. Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013 Dec 19;8(12):e82793.

[4] Maserejian NN. et al. Low dietary or supplemental zinc is associated with depression symptoms among women, but not men, in a population-based epidemiological survey. J Affect Disord. 2012 Feb;136(3):781-8.

[5] Siwek M. et al. Zinc as a marker of affective disorders. Pharmacol Rep. 2013;65(6):1512-8.

[6] Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):646-52.

[7] Ranjbar E. et al. Effects of zinc supplementation in patients with major depression: a randomized clinical trial. Iran J Psychiatry. 2013 Jun;8(2):73-9.

[8] Lai J. et al. The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials. J Affect Disord. 2012 Jan;136(1-2):e31-9.

[9] Tassabehji NM. et al. Zinc deficiency induces depression-like symptoms in adult rats. Physiology & Behavior. 2008; 95: 365–369

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Vashum KP, McEvoy M, Milton AH, McElduff P, Hure A, Byles J, & Attia J (2014). Dietary zinc is associated with a lower incidence of depression: findings from two Australian cohorts. Journal of affective disorders, 166, 249-57 PMID: 25012438