Gluten related illnesses and severe mental disorders: a comprehensive review

Highlights

• Epidemiological studies indicate the existence of an association between coeliac disease and severe mental disorders.

• The immune response to gluten could be different in individuals with schizophrenia and mood disorders.

• There are few evidence that gluten-free diets could be beneficial for individuals with severe mental disorders.

Abstract

The putative role of gluten in the pathophysiology of severe mental illnesses remains uncertain and there is doubt about the possible benefit of gluten-free diets for individuals affected by psychosis and mood disorders. The objective of this review was to summarize the findings linking gluten related conditions to pathophysiological substrates implicated in schizophrenia and mood disorders and review the evidences of potential benefits of glute-free diets in these populations. A literature search was conducted within PubMed and Scielo databases including references from inception until March 1st 2017. The strategy search was to use the key words “gluten”, “celiac disease”, “wheat”, “bipolar disorder”, “mood disorders”, “psychosis”, “schizophrenia”, “depression”. In the review about the potential efficacy of gluten-free diets in severe mental illnesses, we included only studies with original data, including cross sectional and longitudinal studies and clinical trials. Book chapters, review articles and meta-analysis and republished data were excluded. Although the current available evidences suggest that people with celiac disease or gluten allergy could have a slightly higher risk of schizophrenia and mood disorders compared to the general population, the literature review reveals significant inaccuracies in the data. There is insufficient evidence to recommend gluten-free diets for populations with psychosis and mood disorders.

Introduction

Gluten is a glycoprotein composed by two components: gliadin and glutenin. It is an element present in the regular diet of the majority of western countries and is found in wheat, barley, rye and, in a lower proportion, in oats. In addition, gluten has been added to processed food to improve its texture and increase its volume (San Mauro et al., 2014). Wheat became very popular relative to other cereals mainly due to the flour with gluten properties of produce an elastic network resulting in a light and optimally chewy bread (Bressan and Kramer, 2016). Nevertheless, in the last decade, gluten was popularly stigmatized and, as a result, gluten-free diets have become increasingly prevalent. This trend was particularly evident in North America, where in 2013, 30 percent of U.S. adults reported reducing or eliminating gluten in their diets (Moore, 2014). Moore (2014), in a qualitative study, described a broadening of lay understanding of gluten-related diseases, the undermining of biomedical authority (especially by individuals reporting negative experiences with doctors); and a trend to gluten-free adherents to make self-diagnosis and diagnose others with gluten-related diseases (Moore, 2014).

Interestingly, diet has been recognized as a potentially influencer in risk and resilience for mental illness. A well-known example is the fish oil Omega-3’s effects on depression (Deacon et al., 2017, Messamore et al., 2017). In this sense, it is possible to hypothesize that a nutritional compound, such as gluten, may affect mental illnesses development and/or its underlying mechanisms. Indeed, there are some studies suggesting the existence of an association between gluten-related diseases (including celiac disease (CD) and gluten allergy) and psychiatric and neurologic diseases, such as epilepsy (Antigoni et al., 2007, Bashiri et al., 2016, Hernandez et al., 1998), ataxia (Hadjivassiliou et al., 2003, Luostarinen et al., 2001) and autism (Ghalichi et al., 2016). Nevertheless, the literature on the potential role of gluten in the pathophysiology of mental illnesses remains scarce and disparate. More recently, some studies raised the possibility that mental disorders such as schizophrenia and mood disorders could be associated to CD. This hypothesis was reinforced by a significant body of evidence supporting the presence of autoimmune dysfunctions in those mental conditions (Benros et al., 2013, Benros et al., 2011, Eaton et al., 2010, Eaton et al., 2006, Euesden et al., 2017, Kayser, 2014, Shen et al., 2015) and the increased risk of individuals with autoimmune illnesses to developing severe mental disorders (Eaton et al., 2010, Eaton et al., 2006, Euesden et al., 2017, Kayser, 2014, Shen et al., 2015). Considering that the clinician is often questioned by individuals with severe mental ilnesses about possible benefits of gluten-free diets, a comprehensive review on the subject is necessary.

The objective of this study was to review the evidence linking CD, wheat allergy and gluten sensitivity to schizophrenia and mood disorders, to discuss possible contributions of the immune response to gluten in the pathophysiology of these mental conditions and to critically assess the intervention studies with gluten-free diet in clinical and functional outcomes (Fig. 1).