Mood Disorders and Gluten: It's Not All in Your Mind! A Systematic Review with Meta-Analysis.

Gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. However, the directionality of the relationship remains unclear. We performed a systematic review of prospective studies for effects of gluten on mood symptoms in patients with or without gluten-related disorders. Six electronic databases (CINAHL, PsycINFO, Medline, Web of Science, Scopus and Cochrane Library) were searched, from inception to 8 August 2018, for prospective studies published in English. Meta-analyses with random-effects were performed. Three randomised-controlled trials and 10 longitudinal studies comprising 1139 participants fit the inclusion criteria. A gluten-free diet (GFD) significantly improved pooled depressive symptom scores in GFD-treated patients (Standardised Mean Difference (SMD) -0.37, 95% confidence interval (CI) -0.55 to -0.20; < 0.0001), with no difference in mean scores between patients and healthy controls after one year (SMD 0.01, 95% CI -0.18 to 0.20, = 0.94). There was a tendency towards worsening symptoms for non-coeliac gluten sensitive patients during a blinded gluten challenge vs. placebo (SMD 0.21, 95% CI -0.58 to 0.15; = 0.25). Our review supports the association between mood disorders and gluten intake in susceptible individuals. The effects of a GFD on mood in subjects without gluten-related disorders should be considered in future research.