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.
作为全球最主要的非致命疾病负担，抑郁症（MDD）早已成为医学研究的热点领域，但其发病机制至今尚不明确，这直接影响到抑郁症的防治策略选择。在细胞因子学说中，认为促炎症性细胞因子会通过血脑屏障影响脑内的单胺类神经递质和谷氨酸能神经传递，表明慢性低度炎症与抑郁症关联性较强。然而，在抑郁症的首次发作之前，促炎细胞因子是否已经异常升高却并无报道证实。因此本文将184名首次抑郁障碍发作的青少年患者作为研究对象，并将相同数量的同期健康个体作为对照。所有被试均检测8项指标：血清超敏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、同型半胱氨酸（Hcy）、S100钙结合蛋白B（S100B）和二胺氧化酶（DAO）等。结果两组血清hs-CRP、TNF-α水平差异无统计学意义，这与已有的研究结果不同，表明炎症因子可能不是抑郁症首次发作的原因。与此同时我们发现的是，病例组胺水平（12.35μm）明显高于对照组（9.73μm，P＜0.001），同时反映血脑屏障通透性的指标S100B也升高，证实高水平的血清组胺导致血脑屏障的通透性增加，进而引发与抑郁症相关的一系列精神症状的可能性。对病例组组织胺水平升高的原因进行分析，IgE（病例组37.87% vs 对照组22.3%）与IgG（病例组89.67% vs 对照组13.04%）的阳性率病例组均高于对照组，但是IgG两组之间差异更加显著，表明食物特异性免疫球蛋白G是组织胺升高的主要原因。因此本研究认为：长期慢性的食物不耐受导致的组胺升高是抑郁症发病的危险因素。抑郁症早期的发病机制可能不同于其他阶段，在抑郁症的早期发病机制中，应强调慢性食物抗原特异性IgG介导的超敏反应或慢性食物不耐受的作用，而不是慢性低度炎症。相应地，在防治策略上，我们提出了组织胺释放抑制剂对抑郁症治疗的可能性。





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