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.

中文翻译：

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慢性食品抗原特异性IgG介导的超敏反应是青少年抑郁症的危险因素。

重度抑郁症（MDD）是全世界最常见的非致命疾病负担。据报道，系统性慢性低度炎症通过影响单胺能和谷氨酸能神经传递而与MDD进展相关。然而，在抑郁症的首发之前，各种促炎细胞因子是否异常升高仍不清楚。在这里，我们评估了184名正在经历抑郁症首发的青春期患者，并以相同数量的健康个体作为对照。我们检测了高敏C反应蛋白（hs-CRP），肿瘤坏死因子-α（TNF-α），IgE，14种不同类型的食物抗原特异性IgG，组胺，高半胱氨酸，S100钙结合的血清水平蛋白B和二胺氧化酶。两组之间的hs-CRP或TNF-α血清水平无明显差异。然而，患者的组胺水平（12.35μM）显着高于对照组（9.73μM，P <0.001，Mann-Whitney U检验）。此外，在患者组中还发现血清食物抗原特异性IgG阳性率明显更高。此外，超过80％的患者表现出长期的食物耐受性，血清组胺水平升高，导致血脑屏障通透性过高，这先前与MDD的发病机理有关。因此，长期高水平的血清组胺可能是抑郁症的危险因素，而抗组胺剂的释放可能代表抑郁症治疗的一种新的治疗策略。