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Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression.
Translational Psychiatry ( IF 6.8 ) Pub Date : 2020-08-24 , DOI: 10.1038/s41398-020-00979-z
Carmen Schiweck 1, 2 , Stephan Claes 1 , Lukas Van Oudenhove 3, 4 , Ginette Lafit 1, 5 , Thomas Vaessen 1 , Gommaar Op de Beeck 6 , Raf Berghmans 6 , Annemarie Wijkhuijs 7 , Norbert Müller 8 , Volker Arolt 9, 10 , Hemmo Drexhage 7 , Elske Vrieze 1
Affiliation  

Circulating monocytes contribute to inflammatory processes. We here validate abnormal expression of inflammation-related genes in monocytes of a large and well-characterised group of MDD patients, and relate the outcomes to pertinent clinical characteristics. Thirty-two genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD, and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene- expression data were related to age, sex, BMI, depression severity, childhood adversity (CA) and suicide risk (SR). Three distinct gene profiles were identified within the MDD group (downregulated, mixed upregulated and strongly upregulated genes). Patients in the merged upregulated groups had a significantly higher prevalence of CA and high SR. Using hierarchical clustering of the genes, we found a cluster of mainly cytokine (production)-related genes; patients with SR had a significantly higher expression of this cluster than patients without SR (particularly for IL-6, IL1A and IL1B). Such difference did not emerge for patients with and without CA. A downregulated gene profile was found for patients not exposed to CA and without SR (particularly for glucocorticoid-signalling genes NR3C1a and HSPA1/B). No inflammatory changes were observed for healthy controls exposed to CA. Our data show that inflammatory activation in MDD is not uniform, and that immunologically discernible phenotypes of depression can be linked to CA and high SR. The absence of monocyte inflammatory activation in healthy controls exposed to CA suggests an inflammatory involvement in MDD-prone individuals exposed to early stressors, but not healthy controls.



中文翻译:

童年创伤、自杀风险和抑郁症的炎症表型:来自单核细胞基因表达的见解。

循环单核细胞有助于炎症过程。我们在此验证了一大群特征良好的 MDD 患者单核细胞中炎症相关基因的异常表达,并将结果与​​相关的临床特征联系起来。对 197 名 MDD 患者和在 EU-MOODINFLAME 项目期间收集的 151 名对照者评估了先前确定的炎症相关基因特征的 32 个基因。单核细胞基因表达数据与年龄、性别、BMI、抑郁严重程度、童年逆境(CA)和自杀风险(SR)有关。在 MDD 组中鉴定了三种不同的基因谱(下调、混合上调和强烈上调基因)。合并上调组的患者 CA 和高 SR 的患病率显着更高。使用基因的层次聚类,我们发现了一组主要与细胞因子(生产)相关的基因;患有 SR 的患者比没有 SR 的患者具有显着更高的该簇表达(尤其是 IL-6、IL1A 和 IL1B)。有和没有 CA 的患者没有出现这种差异。未暴露于 CA 和未 SR 的患者(尤其是糖皮质激素信号基因 NR3C1a 和 HSPA1/B)发现了下调的基因谱。对于暴露于 CA 的健康对照,没有观察到炎症变化。我们的数据表明,MDD 中的炎症激活并不均匀,免疫学上可辨别的抑郁表型可能与 CA 和高 SR 有关。在暴露于 CA 的健康对照中,单核细胞炎症激活的缺失表明,在暴露于早期压力源的 MDD 易感个体中存在炎症参与,但在健康对照中则不然。

更新日期:2020-08-24
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