IMMUNOLOGICAL GLUTEN SENSITIVITY IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER
Authors: Motoyama *Mikuni , Yamada Hisashi , Maebayashi Kensei , Yoshimura Chiho , Matsunaga Hisato 
Published: February 2025

Abstract

Background
Gluten sensitivity is a syndrome characterized by several physical and psychological symptoms such as abdominal pain, constipation, diarrhea, headache, foggy brain, tiredness, anxiety, and major depressive disorder, related to the ingestion of gluten. Although anti-gliadin IgG antibody has been presented as an immunological marker of gluten sensitivity, the diagnostic criteria have not been established yet, and much remains unclear about gluten sensitivity. Hyogo Medical University has the specialized outpatient unit for gluten sensitivity since 2019. Although there are reports that older adults with gluten sensitivity have a higher prevalence of major depressive disorder than those without gluten sensitivity, and RCTs have reported that gluten intake in patients with gluten sensitivity with irritable bowel syndrome worsened depressive symptoms, no studies have investigated immunological gluten sensitivity in patients with major depressive disorder. We present our findings regarding relationship between immunological gluten sensitivity, physical and psychological symptoms in patients with major depressive disorder.

Method
From 2020 through 2023, patients with major depressive disorder aged 20-70 years who visited Hyogo Medical University Hospital and healthy controls matched by age and gender were recruited. We determined immunological gluten sensitivity using anti-gliadin IgG antibody, and psychiatric and physical symptoms were evaluated by medical interview and self-administered questionnaire. This study was approved by the ethics committee at Hyogo Medical University. Detailed explanations of the study procedures were provided to each participant at the time we received their informed consent.

Results
The final sample consisted of 24 patients with major depressive disorder and 61 healthy controls participated. Among 24 patients with major depressive disorder, 9 (37.5%) were determined as immunological gluten sensitivity. Of the 61 healthy controls, 6 (9.8%) were determined as immunological gluten sensitivity. Immunological gluten sensitivity in patients with major depressive disorder was significantly higher than that in the healthy subjects (p&lt;0.01). Among patients with major depressive disorder, immunological gluten sensitivity had a higher Clinical Global Impression-Severity Scale and a lower quality of life related to work or housework than the non-immunological gluten sensitivity, but there were no differences in the presence of irritable bowel syndrome, subjective symptoms of gluten sensitivity such as diarrhea, abdominal pain. Treatment-resistant major depressive disorder was 56% in the immunological gluten sensitivity and 47% in the non-immunological gluten sensitivity with also no significant difference.

Discussion
A higher prevalence of immunological gluten sensitivity was found in patients with major depressive disorder than in the healthy group, but the association with treatment resistance is unclear. Although in patients with major depressive disorder with immunological gluten sensitivity were found to be more disturbed in their usual lives than those without immunological gluten sensitivity, there were no differences in prevalence of treatment resistance or in scales of depressive and anxiety symptoms, suggesting that immunological gluten sensitivity is related to the onset of major depressive disorder rather than to its effect on depressive symptoms.