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

Genomics Proteomics Bioinformatics. 2019 Apr;17(2):183-189. doi: 10.1016/j.gpb.2019.05.002. Epub 2019 Jun 21.


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.

Keywords: Blood–brain barrier; Histamine; Hypersensitivity reaction; Inflammation; Major depressive disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • C-Reactive Protein
  • Chronic Disease
  • Cytokines
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / epidemiology*
  • Depressive Disorder, Major / etiology*
  • Female
  • Food Hypersensitivity / blood
  • Food Hypersensitivity / complications*
  • Histamine / blood
  • Homocysteine / blood
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Inflammation Mediators / blood
  • Male
  • Risk Factors
  • S100 Calcium Binding Protein beta Subunit / blood
  • Young Adult


  • Biomarkers
  • Cytokines
  • Immunoglobulin G
  • Inflammation Mediators
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Homocysteine
  • Immunoglobulin E
  • Histamine
  • C-Reactive Protein