Chronic Food Antigen-specific IgG-mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder

Ran Tao,Zhicheng Fu,Lijun Xiao

doi:10.1016/j.gpb.2019.05.002

Abstract

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann–Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood–brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.

Highlights

Major depressive disorder (MDD) is a kind of mental disease that affected approximately 216 million people (3% of the world’s population) in 2015 and that is projected to have the secondhighest global burden of disease in all age groups and sexes by 2020 [1]
To determine whether the elevated serum histamine level was associated with an abnormal pathway of histamine degradation, we examined the level of histamine metabolizing enzyme diamine oxidase (DAO) in these two groups, and no significant difference was found
We believe that adolescent depression may result from immune disorders, metabolic disorders, and nutritional imbalances

Summary

Introduction

Major depressive disorder (MDD) is a kind of mental disease that affected approximately 216 million people (3% of the world’s population) in 2015 and that is projected to have the secondhighest global burden of disease in all age groups and sexes by 2020 [1]. Previous findings have shown that at least some subtypes of depression are associated with chronic low-grade systemic inflammation in adults [5,6]. The levels of serum inflammatory markers are increased in some adult MDD patients. The level of C-reactive protein (CRP), which reflects the state of systemic inflammation, is elevated in the serum of at least 30% of MDD patients [7,8]. Serum levels of proinflammatory cytokines, such as tumor necrosis factor-a (TNF-a), are higher in patients with depression than in those without depression or anxiety [9,10,11]. Diseases related to chronic inflammation, such as cardiovascular diseases, inflammatory bowel diseases, and rheumatoid diseases, are associated with a high risk of MDD [12,13]

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