Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are associated with cytokine networks and their intricate interactions with metabolic syndrome

IF 3.5 2区医学 Q2 PSYCHIATRY

Journal of Psychosomatic Research Pub Date : 2024-10-10 DOI:10.1016/j.jpsychores.2024.111951

Michael Maes , Ketsupar Jirakran , Asara Vasupanrajit , Bo Zhou , Chavit Tunvirachaisakul , Abbas F. Almulla

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引用次数: 0

Abstract

Objectives

To identify alterations in the immune profiles in outpatients with major depression (MDD), and its associations with key features, such as suicidal ideation, neuroticism, cognitive symptoms, and the depression phenome while accounting for metabolic syndrome (MetS).

Methods

In this case-control study, we assayed 48 serum cytokines, chemokines, and growth factors in 67 healthy controls and 66 MDD outpatients. Around 50 % of the outpatient MDD and control participants had a diagnosis of MetS.

Results

Ten differentially expressed proteins (DEPs) were upregulated in outpatient MDD (i.e., CXCL12, tumor necrosis factor [TNF]β, platelet-derived growth factor [PDGF], CCL11, interleukins [IL]9, IL4, CCL5, CCL2, CCL4, IL1 receptor antagonist [IL1RN]), indicating an immune and defense response. Six DEPs were downregulated (vascular endothelial growth factor A [VEGFA], IL12, CCL3, colony stimulating factor [CSF]1, IL1B, nerve growth factor [NGF]), indicating lowered neurogenesis and neuron death regulation. Significant interactions between outpatient MDD and MetS caused a) substantial increases in IL4, IL17, TNF, TNFB, CCL2, CCL5, PDGF, IL1RN; and b) downregulation of VEGFA and FGF. A large part of the variance in neuroticism (26 %), suicidal behaviors (23 %), and the MDD phenome (31 %) was predicted by immunological data and interactions between MetS and CCL5, TNFB or VEGFA.

Conclusion

Outpatient MDD is characterized by a cytokine profile with neurotoxic potential which partly explains neuroticism, suicidal behaviors, and the phenome's severity. Lowered IL-10 and activated cytokine profiles with neurotoxic potential are characteristics of outpatient MDD and other depression phenotypes, including severe first-episode inpatient MDD. The presence of MetS in outpatient MDD considerably activates immune profiles with neurotoxic potential. Consequently, immune studies in MDD should always be performed in subjects with and without MetS.

查看原文本刊更多论文

重度抑郁症、神经质、自杀行为和抑郁症严重程度与细胞因子网络及其与代谢综合征之间错综复杂的相互作用有关

方法在这项病例对照研究中，我们检测了 67 名健康对照者和 66 名重度抑郁症门诊患者的 48 种血清细胞因子、趋化因子和生长因子。结果10种差异表达蛋白（DEPs）在MDD门诊患者中上调（即CXCL12、肿瘤坏死因子[TNF]β、血小板衍生生长因子[PDGF]、CCL11、白细胞介素[IL]9、IL4、CCL5、CCL2、CCL4、IL1受体拮抗剂[IL1RN]），表明存在免疫和防御反应。六种 DEPs 下调（血管内皮生长因子 A [VEGFA]、IL12、CCL3、集落刺激因子 [CSF]1、IL1B、神经生长因子 [NGF]），表明神经发生和神经元死亡调节功能降低。门诊 MDD 和 MetS 之间的显著交互作用导致：a）IL4、IL17、TNF、TNFB、CCL2、CCL5、PDGF、IL1RN 大量增加；b）VEGFA 和 FGF 下调。免疫学数据以及 MetS 与 CCL5、TNFB 或 VEGFA 之间的相互作用预测了神经质（26%）、自杀行为（23%）和 MDD 表型（31%）的大部分差异。IL-10降低和具有神经毒性的细胞因子激活是门诊MDD和其他抑郁症表型的特征，包括严重的首发住院MDD。门诊 MDD 中 MetS 的存在大大激活了具有神经毒性潜能的免疫特征。因此，对 MDD 的免疫研究应始终在有 MetS 和无 MetS 的受试者中进行。

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来源期刊

Journal of Psychosomatic Research 医学-精神病学

CiteScore

7.40

自引率

6.40%

发文量

314

审稿时长

6.2 weeks

期刊介绍： The Journal of Psychosomatic Research is a multidisciplinary research journal covering all aspects of the relationships between psychology and medicine. The scope is broad and ranges from basic human biological and psychological research to evaluations of treatment and services. Papers will normally be concerned with illness or patients rather than studies of healthy populations. Studies concerning special populations, such as the elderly and children and adolescents, are welcome. In addition to peer-reviewed original papers, the journal publishes editorials, reviews, and other papers related to the journal''s aims.