A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic inflammation in MDD. RT-qPCR was used to measure mRNA expression of key organellar genes from peripheral blood mononuclear cells (PBMCs) isolated from 186 MDD and 67 healthy control (HC) subjects. The comparative C_T (2^-ΔΔCT) method was applied to quantify mRNA expression using GAPDH as the reference gene. After controlling for age, sex, BMI, and medication status using linear regression models, expression of the inflammasome (NLRC4 and NLRP3) and the ER stress (XBP1u, XBP1s, and ATF4) genes was found to be significantly increased in the MDD versus the HC group. Sensitivity analyses excluding covariates yielded similar results. After excluding outliers, expression of the inflammasome genes was no longer statistically significant but expression of the ER stress genes (XBP1u, XBP1s, and ATF4) remained significant and the mitochondrial biogenesis gene, MFN2, was significantly increased in the MDD group. NLRC4 and MFN2 were positively correlated with serum C-reactive protein concentrations, while ASC trended significant. The altered expression of inflammasome activation, ER stress, and mitochondrial biogenesis pathway components suggest that dysfunction of these organelles may play a role in the pathogenesis of MDD.

重度抑郁症 (MDD) 的一个亚型以免疫系统功能障碍为特征，但这些免疫变化的细胞内起源仍不清楚。在这里，我们检验了这样的假设：内质网 (ER) 应激、炎症小体活性和线粒体生物合成的异常导致 MDD 全身炎症的发生。 RT-qPCR 用于测量从 186 名 MDD 和 67 名健康对照 (HC) 受试者中分离的外周血单核细胞 (PBMC) 中关键细胞器基因的 mRNA 表达。以GAPDH为内参基因，采用比较_CT （2 ^-ΔΔCT ）法定量mRNA表达量。使用线性回归模型控制年龄、性别、BMI 和药物状态后，发现 MDD 中炎症小体（ NLRC4和NLRP3 ）和 ER 应激（ XBP1u、XBP1s和ATF4 ）基因的表达显着增加。 HC组。排除协变量的敏感性分析得出了类似的结果。排除异常值后，MDD 组中炎性体基因的表达不再具有统计学意义，但 ER 应激基因（ XBP1u、XBP1s和ATF4 ）的表达仍然显着，并且线粒体生物发生基因MFN2显着增加。 NLRC4和MFN2与血清C反应蛋白浓度呈正相关，而ASC趋势显着。炎症小体激活、内质网应激和线粒体生物合成途径成分表达的改变表明这些细胞器的功能障碍可能在 MDD 的发病机制中发挥作用。