Maes Clinics @ TRIA, Piyavate Hospital, Bangkok, Thailand.
J Affect Disord. 2012 Feb;136(3):386-92. doi: 10.1016/j.jad.2011.11.016. Epub 2011 Dec 12.
Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation.
5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.
The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes.
The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization (kindling) and staging of depression are in part based on progressive autoimmune responses.
抑郁症的特征是炎症和细胞介导的免疫（CMI）激活以及针对多种自身表位的自身免疫反应。有证据表明，抑郁症中的炎症反应导致 5-HT 代谢功能障碍，例如降低 5-HT 前体色氨酸并上调 5-HT 受体 mRNA。这项研究旨在检查针对 5-HT 的自身免疫活性与 CMI 激活和炎症的关系。
在主要抑郁症患者（n=109）和正常对照组（n=35）中，检查 5-HT 抗体与血清中新蝶呤和溶菌酶以及血浆中促炎细胞因子（PIC）即白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNFα）的关系。使用汉密尔顿抑郁评定量表（HDRS）评估抑郁严重程度，使用纤维肌痛和慢性疲劳综合征（FF）评定量表评估疲劳和躯体症状严重程度。
抗 5-HT 抗体活性在抑郁症患者（54.1%），尤其是在忧郁症患者（82.9%）中的发生率明显高于对照组（5.7%）。具有阳性 5-HT 抗体的患者显示血清新蝶呤和溶菌酶升高，血浆 TNFα 和 IL-1 升高；HDRS 和 FF 量表评分升高，躯体症状更多，包括不适和神经认知功能障碍。5-HT 自身免疫活性与之前的抑郁发作次数之间存在显著相关性。
针对 5-HT 的自身免疫反应可能在抑郁症的病理生理学和重度抑郁症的发作中起作用。针对 5-HT 的自身免疫活性与炎症/CMI 激活之间的强关联可以用这些因素之间的多种相互关系来解释。以前的抑郁发作次数增加会增加针对 5-HT 的自身免疫活性的发生率，而这反过来又可能增加发生新的抑郁发作的可能性。这些发现表明，抑郁的致敏（点燃）和分期部分基于进行性自身免疫反应。
