Characterization of the signature of peripheral innate immunity in women with later-life major depressive disorder
Characterization of the signature of peripheral innate immunity in women with later-life major depressive disorder
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DOI：
10.1016/j.bbi.2020.03.018
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发表时间：
2020-07-01
影响因子：
15.1
通讯作者：
Fukuda, Masato
中科院分区：
文献类型：
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作者：
Miyata, Shigeo;Yamagata, Hirotaka;Fukuda, Masato
女性晚年抑郁症患病率高于男性。然而，老年患者抑郁症病理生理学的性别差异尚不完全清楚。在这里，我们对患有重度抑郁症（在此背景下称为晚年抑郁症（LLD））的中老年患者的白细胞进行了基因表达谱分析，并描述了 LLD 的性别依赖性病理生理学。使用了从 LLD 患者（年龄 >= 50 岁）（32 名男性和 39 名女性）和年龄匹配的健康个体（20 名男性和 24 名女性）的白细胞中获得的微阵列数据集。通过比较患者和健康个体之间的表达水平来确定差异表达的探针，然后进行功能注释分析（Ingenuity Pathway Analysis、Reactome Pathway Analysis和cell-typeufficient Analysis）。共有1656个探针在LLD女性中差异表达，但在LLD男性中只有3个基因差异表达。 LLD 雌性中的差异表达基因与白细胞外渗信号、Tec 激酶信号和先天免疫反应相关。上调的基因与骨髓谱系细胞如CD14(+)单核细胞相关。相反，下调的基因与CD4(+)和CD8(+) T细胞相关。LLD女性的白细胞中存在显着的先天免疫特征，而男性则没有。由于炎症与抑郁症的病理生理学有关，因此炎症活动的改变可能与女性 LLD 的病理生理学有关。相比之下，异常炎症可能是 LLD 男性的一个罕见特征。
The prevalence of depression in later life is higher in women than in men. However, the sex difference in the pathophysiology of depression in elderly patients is not fully understood. Here, we performed gene expression profiling in leukocytes of middle-aged and elderly patients with major depressive disorder, termed later-life depression (LLD) in this context, and we characterized the sex-dependent pathophysiology of LLD.A microarray dataset obtained from leukocytes of patients (aged >= 50 years) with LLD (32 males and 39 females) and age-matched healthy individuals (20 males and 24 females) was used. Differentially expressed probes were determined by comparing the expression levels between patients and healthy individuals, and then functional annotation analyses (Ingenuity Pathway Analysis, Reactome pathway analysis, and cell-type enrichment analysis) were performed.A total of 1656 probes were differentially expressed in LLD females, but only 3 genes were differentially expressed in LLD males. The differentially expressed genes in LLD females were relevant to leukocyte extravasation signaling, Tec kinase signaling and the innate immune response. The upregulated genes were relevant to myeloid lineage cells such as CD14(+) monocytes. In contrast, the downregulated genes were relevant to CD4(+) and CD8(+) T cells.Remarkable innate immune signatures are present in the leukocytes of LLD females but not males. Because inflammation is involved in the pathophysiology of depression, the altered inflammatory activity may be involved in the pathophysiology of LLD in women. In contrast, abnormal inflammation may be an uncommon feature in LLD males.