Department of Psychiatry and Medical Psychology, Medical Faculty, Medical University of Plovdiv, Plovdiv, Bulgaria; Research Institute, Medical University, Plovdiv, Bulgaria.
Monnet Research Center, Louvain-La-Neuve, Belgium.
Nitric Oxide. 2021 Jan 1;106:45-54. doi: 10.1016/j.niox.2020.11.001. Epub 2020 Nov 10.
Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs) and nitric oxide (NO)-adducts. These responses were not examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, azelaic acid, and NO-adducts were determined in 35 healthy controls, and 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum peroxides, IgG to oxidized LDL (oxLDL), and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs and NO-adducts (OSENO) were significantly higher in MDD and BP1 as compared with controls, and IgM to OSEs higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, a latent vector extracted from IgM to OSENO, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSENO, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSENO, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.
重度抑郁症伴随着氧化特异性表位（OSE）和一氧化氮（NO）加合物的 IgM 介导的自身免疫反应增加。这些反应在 1 型双相障碍（BP1）和 BP2 中尚未进行研究。在 35 名健康对照者和 47 名重度抑郁（MDD）、29 名 BP1 和 25 名 BP2 患者中，测定了对丙二醛（MDA）、磷脂酰肌醇、油酸、壬二酸和 NO 加合物的 IgM 反应。我们还测量了血清过氧化物、IgG 对氧化 LDL（oxLDL）和 IgM/IgA 对脂多糖（LPS）的反应。与对照组相比，MDD 和 BP1 患者的 OSE 和 NO 加合物（OSENO）的 IgM 反应明显更高，而 MDD 患者的 OSE 高于 BP2。偏最小二乘（PLS）分析显示，情绪障碍临床表型的 57.7%的方差可以用发作次数、从 IgM 到 OSENO、IgG 到 oxLDL 和过氧化物中提取的潜在向量来解释。IgA/IgM 对 LPS 的特异性间接影响对临床表型有显著影响，其受过氧化物、IgM OSENO 和 IgG oxLDL 的介导。使用 PLS，我们构建了一个数据驱动的分类网络，该网络将因果体（增加的血浆 LPS 负荷）、不良结局途径（即神经情感毒性）和情绪障碍的临床表型特征整合在一个数据驱动的模型中。基于这些特征集，聚类分析发现了一个新的诊断类别，其特征是血浆 LPS 负荷、过氧化物、OSE 自身免疫反应和表型评分增加。使用新的分类网络方法，我们构建了一个机制上的跨诊断诊断类别，该类别在 74.3%的情绪障碍患者中显示出神经情感毒性。
