Background

The macrophage theory of depression states that macrophages play an important role in Major Depressive Disorder (MDD).

Methods

MDD patients (N = 140) and healthy controls (N = 120) participated in a cross-sectional study investigating the expression of apoptosis/growth and lipid/cholesterol pathway genes (BAX, BCL10, EGR1, EGR2, HB-EGF, NR1H3, ABCA1, ABCG1, MVK, CD163, HMOX1) in monocytes (macrophage/microglia precursors). Gene expressions were correlated to a set of previously determined and reported inflammation-regulating genes and analyzed with respect to various clinical parameters.

Results

MDD monocytes showed an overexpression of the apoptosis/growth/cholesterol and the TNF genes forming an inter-correlating gene cluster (cluster 3) separate from the previously described inflammation-related gene clusters (containing IL1 and IL6). While upregulation of monocyte gene cluster 3 was a hallmark of monocytes of all MDD patients, upregulation of the inflammation-related clusters was confirmed to be found only in the monocytes of patients with childhood adversity. The latter group also showed a downregulation of the cholesterol metabolism gene MVK, which is known to play an important role in trained immunity and proneness to inflammation.

Conclusions

The upregulation of cluster 3 genes in monocytes of all MDD patients suggests a premature aging of the cells, i.e. mitochondrial apoptotic dysfunction and TNF “inflammaging”, as a general feature of MDD. The overexpression of the IL-1/IL-6 containing inflammation clusters and the downregulation of MVK in monocytes of patients with childhood adversity indicates a shift in this condition to a more severe inflammation form (pyroptosis) of the cells, additional to the signs of premature aging and inflammaging.

中文翻译：

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重度抑郁症中的单核细胞线粒体功能障碍、炎症和炎症性焦亡

背景

抑郁症的巨噬细胞理论指出，巨噬细胞在重度抑郁症（MDD）中起重要作用。

方法

MDD 患者 ( N  = 140) 和健康对照组 ( N  = 120) 参与了一项横断面研究，调查细胞凋亡/生长和脂质/胆固醇通路基因（BAX、BCL10、EGR1、EGR2、HB-EGF、NR1H3、单核细胞（巨噬细胞/小胶质细胞前体）中的 ABCA1、ABCG1、MVK、CD163、HMOX1）。基因表达与一组先前确定和报告的炎症调节基因相关，并针对各种临床参数进行分析。

结果

MDD 单核细胞显示细胞凋亡/生长/胆固醇和 TNF 基因的过表达，形成一个相互关联的基因簇（簇 3），与先前描述的炎症相关基因簇（包含 IL1 和 IL6）分开。虽然单核细胞基因簇 3 的上调是所有 MDD 患者单核细胞的标志，但证实炎症相关簇的上调仅在儿童逆境患者的单核细胞中发现。后一组还显示出胆固醇代谢基因 MVK 的下调，已知该基因在训练的免疫力和炎症倾向中起重要作用。

结论

所有 MDD 患者单核细胞中簇 3 基因的上调表明细胞过早衰老，即线粒体凋亡功能障碍和 TNF“炎症”，这是 MDD 的一般特征。在儿童逆境患者的单核细胞中，含有炎症簇的 IL-1/IL-6 的过度表达和 MVK 的下调表明这种情况向细胞的更严重的炎症形式（焦亡）转变，此外还有以下迹象：过早衰老和炎症。