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Gluten and Schizophrenia: What’s Next?

Nada Boutrid, Hakim Rahmoune*, Mounira Amrane

LMCVGN Research Laboratory, Setif-1 University, Algeria

Abstract: This letter is summarizing the pathophysiological, clinical and possible therapeutic relationship between dietary gluten and schizophrenia. In a short, updated overview we would highlight the mounting evidence of the possible efficiency of a gluten-free diet and the need of considering this option in managing schizophrenia.

Keywords: schizophrenia, gluten, celiac disease

Received September 27, 2021; Revised November 02, 2021; Accepted November 10, 2021

Citation: Nada Boutrid, Hakim Rahmoune, Mounira Amrane, Gluten and Schizophrenia: What’s Next?. International Journal of Celiac Disease, 9 (3). 89-90. January 2021. doi:10.12691/ijcd-9-3-3

Dear Editor,

There is an increasing scientific focus on the peculiar association of dietary gluten with schizophrenia, its possible connections and the eventual efficiency of a gluten-free diet.

A rapid glance at Pubmed® for articles about Schizophrenia and Gluten/Celiac disease confirms this growing interest (Figure 1).

Regarding schizophrenia management, the non-pharmacological approach through gluten-free diet deserves deep attention, as growing evidence suggests that immune-inflammatory triggers (including gluten) might be behind the scene.

One-third of people with schizophrenia have elevated IgG anti-gliadin (AGA IgG) and logistic regressions showed recently an association between AGA IgG and Glutamate Ionotropic Receptor NMDA Type Subunit Associated with protein 1 (GRINA) IgG; indicating a possible mimicry disrupting the glutamate system [2].

Likewise, the gluten-reactive Transglutaminase-6 predominant in neurons under physiological conditions has been incriminated in schizophrenia [3].

Figure 1. (Pubmed® Search for: schizophrenia [Title/abstract] (celiac [Title/abstract] OR gluten [Title/abstract] OR coeliac [Title/abstract])) (The dotted line depicts the chronological trend)

Regarding the clinical aspects, a 2018 meta-analysis found a significantly higher risk of schizophrenia among celiac patients compared to those without celiac disease (odds ratio = 2.03) [4] and, inversely, a systematic review confirmed the strong association between gluten-free diet and better outcomes in schizophrenia such as decreased extrapyramidal symptoms and improved behavior [5].

Finally, a recently published systematic review explored the last decade papers (randomized controlled and clinical trials) investigating the potential relationship between diet and mental disorders. This review concluded that excluding (or limiting) dietary gluten would have beneficial effects for patients with schizophrenia [6].

Thus, gluten avoidance may play a role in managing such devastating neurological disorders as schizophrenia and, specifically, stratifying patients according to their gliadin antibodies status would pave the way to individualized care through a dedicated gluten-free diet.

Acknowledgements

N. Boutrid, H. Rahmoune, M. Amrane (from LMCVGN laboratory) are supported by the Directorate General for Scientific Research and Technological Development (DGRSDT), MESRS, Algeria.

The sponsor had no involvement in the collection, analysis and interpretation of data nor in the writing of the manuscript.

References

[1]   | PubMed [Internet]. PubMed. [accessed on Aug 4th, 2021]. Available at: https://pubmed.ncbi.nlm.nih.gov/.

[2]  
Čiháková D, Eaton WW, Talor MV, Harkus UH, Demyanovich H, Rodriguez K, et al. Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG). Schizophr Res. juin 2019; 208: 414-9.

[3]   | Cascella NG, Santora D, Gregory P, Kelly DL, Fasano A, Eaton WW. Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients. Schizophr Bull. juill 2013; 39(4): 867-71.
[4]   | Wijarnpreecha K, Jaruvongvanich V, Cheungpasitporn W, Ungprasert P. Association between celiac disease and schizophrenia: a meta-analysis. Eur J Gastroenterol Hepatol. avr 2018; 30(4): 442-6.
[5]   | Levinta A, Mukovozov I, Tsoutsoulas C. Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review. Adv Nutr. 1 nov 2018; 9(6): 824-32.
[6]   | Aranburu E, Matias S, Simón E, Larretxi I, Martínez O, Bustamante MÁ, et al. Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review. Nutrients. juin 2021; 13(6): 1894.