Gluten exposure and "feelings of depression"?

Could exposure to dietary gluten affect a person's moods or emotional state?

Well, if the paper by Simone Peters and colleagues [1] (open-access here) is to be believed the answer may very well be yes, at least in some cases, as they report a link between gluten consumption and feelings of depression under [short-term] experimental conditions. If replicated, such a finding may have profound consequences for how we view our relationship between food and mental health and wellbeing.

Bread Ma'am? @ Wikipedia 

I was initially drawn to the Peters paper as a function not only of the subject matter but also the authorship team. Mention of Jessica Biesiekierski in amongst the list of contributors immediately brought back memories of another ground-breaking paper of hers [2] reporting that "Non-celiac gluten intolerance may exist" (see here).

For those who might not know about non-coeliac gluten sensitivity (NCGS), this is a suggestion that outside of the classical connection between gluten and the autoimmune condition coeliac (celiac) disease, there exists something of a spectrum of gluten-related health issues. Some of these issues might have far-reaching implications for an array of conditions including that of autism... at least some autism (see here).

The Peters paper is open-access but a few details might be worthwhile mentioning:

• This was a gold-standard trial in terms of being randomised, double-blind, placebo-controlled and including a cross-over component. What this means is that participants with irritable bowel syndrome (IBS) who were negative for coeliac disease (CD) (though not necessarily tested for the serology of CD) were "asked that they continue on a GFD [gluten-free diet] low in FODMAPS [Fermentable, Oligo-, Di-, Mono-saccharides And Polyols]" for the study duration. Participants were then divided up into groups to receive one of three dietary challenges to their gluten-free diet: gluten supplement (16g/day), whey supplement (16g/day) or placebo for 3 days followed by a wash-out period and then onto the next dietary supplement regime. Neither participants nor researchers knew who got what challenge when.
• As well as adherence to the gluten-free diet and gastrointestinal (GI) symptoms being assessed, salivary cortisol secretions were measured alongside mental state as per the use of the State Trait Personality Inventory (STPI), a self-report measure.
• Results: bearing in mind the relatively small participant group examined (n=22) and the various complications one might expect from undertaking a dietary trial, there was an "increase in [the] STPI state depression score following gluten ingestion compared to placebo". The depression scores were also higher when comparing gluten and whey supplements but did not reach statistical significance. 
• No differences were found with regards to cortisol concentrations across the groups and time-frames nor for GI symptoms.
• The authors conclude that: "Short-term exposure to gluten specifically induced current feelings of depression with no effect on other indices or on emotional disposition". They added: "Such findings might explain why patients with non-coeliac gluten sensitivity feel better on a gluten-free diet despite the continuation of gastrointestinal symptoms".

I have to say that as preliminary as these results might be, I'm quite excited at the implications from them. Yes, I have some professional interest in the relationship between gluten and our mental health / psychology and the so-called gut-brain axis (see here) so am perhaps biased, but to see some research utilising the gold-standard of evidence-based medicine coming up with the findings that they did is something rather grand. As per my opening sentences, replication, replication, replication is the next stop and then we can get really excited.

I note the authors do speculate on why they got the results they did. Cortisol is kinda ruled out as a cause as a function of their findings of no significant change. I might however draw your attention to other findings in this area which should be kept in mind. Serotonin (5-HT) also gets a mention as a potential explanatory reason, which is also interesting bearing in mind the mood connection with this neurotransmitter with appropriate caveats.

Then to some other interesting avenues for further study such as those trillions of beasties which call us and our gut home: the gut microbiota and their potential connection to our mood and psychology (see here). And how about a possible role for gluten exorphins and further the suggestion that opiate antagonists such as naltrexone might be a useful thing to look at? I'd perhaps also be minded to suggest that another possibility not discussed by the authors might be that of intestinal hyperpermeability (leaky gut) also playing a potential role given what we know about gut permeability and gluten [3]. More investigations like this please.

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[1] Peters SL. et al. Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity – an exploratory randomised clinical study. Alimentary Pharmacology & Therapeutics. 2014. doi: 10.1111/apt.12730

[2] Biesiekierski JR. et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011 Mar;106(3):508-14.

[3] Vazquez-Roque MI. et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013 May;144(5):903-911.e3.

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Peters SL, Biesiekierski JR, Yelland GW, Muir JG, & Gibson PR (2014). Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity - an exploratory randomised clinical study. Alimentary pharmacology & therapeutics PMID: 24689456