Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom.
Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
Biol Psychiatry. 2020 Jul 15;88(2):185-196. doi: 10.1016/j.biopsych.2019.11.017. Epub 2019 Dec 2.
Depression has been associated with increased inflammatory proteins, but changes in circulating immune cells are less well defined.
We used multiparametric flow cytometry to count 14 subsets of peripheral blood cells in 206 depression cases and 77 age- and sex-matched controls (N = 283). We used univariate and multivariate analyses to investigate the immunophenotypes associated with depression and depression severity.
Depression cases, compared with controls, had significantly increased immune cell counts, especially neutrophils, CD4 T cells, and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6). Within-group analysis of cases demonstrated significant associations between the severity of depressive symptoms and increased myeloid and CD4 T-cell counts. Depression cases were partitioned into 2 subgroups by forced binary clustering of cell counts: the inflamed depression subgroup (n = 81 out of 206; 39%) had increased monocyte, CD4, and neutrophil counts; increased C-reactive protein and interleukin-6; and more severe depression than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven analysis identified 4 subgroups of depression cases, 2 of which (n = 38 and n = 100; 67% collectively) were associated with increased inflammatory proteins and more severe depression but differed in terms of myeloid and lymphoid cell counts. Results were robust to potentially confounding effects of age, sex, body mass index, recent infection, and tobacco use.
Peripheral immune cell counts were used to distinguish inflamed and uninflamed subgroups of depression and to indicate that there may be mechanistically distinct subgroups of inflamed depression.
抑郁症与炎症蛋白的增加有关，但循环免疫细胞的变化则不太明确。
我们使用多参数流式细胞术对 206 例抑郁症病例和 77 名年龄和性别匹配的对照者（N=283）的外周血 14 个亚群细胞进行计数。我们使用单变量和多变量分析来研究与抑郁症和抑郁严重程度相关的免疫表型。
与对照组相比，抑郁症病例的免疫细胞计数明显增加，尤其是中性粒细胞、CD4 T 细胞和单核细胞，以及炎症蛋白（C 反应蛋白和白细胞介素-6）。病例组的组内分析显示，抑郁症状严重程度与髓样和 CD4 T 细胞计数增加之间存在显著相关性。通过对细胞计数进行强制二元聚类，将抑郁症病例分为 2 个亚组：炎症性抑郁症亚组（n=206 例中的 81 例；39%）表现为单核细胞、CD4 和中性粒细胞计数增加、C 反应蛋白和白细胞介素-6 增加，且抑郁程度较大多数无炎症病例更为严重。放松对二元分类的假设，基于数据驱动的分析确定了 4 个抑郁症病例亚组，其中 2 个（n=38 例和 n=100 例；共计 67%）与炎症蛋白增加和更为严重的抑郁相关，但在髓样和淋巴样细胞计数方面存在差异。结果不受年龄、性别、体重指数、近期感染和吸烟等潜在混杂因素的影响。
外周免疫细胞计数可用于区分炎症性和非炎症性抑郁症亚组，并表明可能存在具有不同机制的炎症性抑郁症亚组。
