Unit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund University, 221 85 Lund, Sweden; Office for Psychiatry and Habilitation, Psychiatric Clinic Helsingborg, Region Skåne, 252 23 Helsingborg, Sweden.
Unit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund University, 221 85 Lund, Sweden.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jul 13;125:110763. doi: 10.1016/j.pnpbp.2023.110763. Epub 2023 Apr 8.
Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depression with and without chronic low-grade inflammation.
We assayed plasma levels of interferon-gamma, tumor necrosis factor-alpha, Interleukin (IL)-10, IL-6, IL-8, and vitamin D in a clinically well-characterized sample of patients with difficult-to-treat depression (n = 263) and healthy controls (n = 46). Serum hs-CRP levels were available in the patient group and were used to define "inflamed depression" (hs-CRP > 3 mg/L). Based on previous studies correlating specific depressive symptoms to inflammatory markers, we calculated a composite score of inflammatory depressive symptoms (Infl-Dep score). A principal component analysis (PCA) was performed to identify patterns of variance in cytokines and vitamin D among patients.
Mean levels of IL-6 and IL-8 were significantly higher in depressed patients compared to controls, also after adjusting for sex, smoking, BMI, and age. None of the other inflammatory markers differed significantly between depressed patients and controls. Two components were extracted using PCA; one showed general cytokine elevations and one represented a pattern where IL-6 and IL-8 were inversely related to vitamin D (IL6-IL8-VitD component). The inflamed subgroup (hs-CRP > 3, n = 51) exhibited significantly higher BMI, higher Infl-Dep scores and higher IL6-IL8-VitD component scores than uninflamed patients (hs-CRP ≤ 3, n = 212). There were no significant differences in overall depression severity or suicidality between the inflamed and uninflamed groups.
Our results support the hypothesis of an inflamed subgroup of depression as a meaningful construct. This subgroup may have certain biological and clinical characteristics and more studies are needed to determine potential clinical implications.
慢性低度炎症可能在抑郁症的病理生理学中起作用，至少在一部分患者中如此。高敏 C 反应蛋白（hs-CRP）已被用于定义具有特定临床特征和症状的炎症亚组抑郁症。在这项研究中，我们研究了伴有和不伴有慢性低度炎症的难治性抑郁症患者的生化和临床特征。
我们测定了一组临床表现明确的难治性抑郁症患者（n=263）和健康对照者（n=46）的血浆干扰素-γ、肿瘤坏死因子-α、白细胞介素（IL）-10、IL-6、IL-8 和维生素 D 水平。患者组可获得血清 hs-CRP 水平，并用于定义“炎症性抑郁症”（hs-CRP＞3mg/L）。基于先前将特定抑郁症状与炎症标志物相关联的研究，我们计算了炎症性抑郁症状的综合评分（Infl-Dep 评分）。对患者的细胞因子和维生素 D 进行主成分分析（PCA），以确定其变异模式。
与对照组相比，抑郁患者的 IL-6 和 IL-8 水平明显升高，即使在调整了性别、吸烟、体重指数和年龄后也是如此。抑郁患者与对照组之间的其他炎症标志物无明显差异。使用 PCA 提取了两个成分；一个显示出一般细胞因子升高，另一个代表 IL-6 和 IL-8 与维生素 D 呈反比关系的模式（IL6-IL8-VitD 成分）。炎症亚组（hs-CRP＞3，n=51）的 BMI 明显较高，Infl-Dep 评分和 IL6-IL8-VitD 成分评分较高，而无炎症患者（hs-CRP≤3，n=212）则较低。炎症组和无炎症组在总体抑郁严重程度或自杀意念方面无显著差异。
我们的结果支持将炎症亚组抑郁症作为一种有意义的构建的假设。该亚组可能具有某些生物学和临床特征，需要更多的研究来确定潜在的临床意义。
