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炎症生物标志物在评估成人重度抑郁症中的预测价值

Predictive Value of Inflammatory Biomarkers in Assessing Major Depression in Adults.

作者信息

Gavril Radu, Dobrin Petru Romeo, Pînzariu Alin Constantin, Moscalu Mihaela, Grigore Radu Gheorghe, Iacob Vlad Teodor, Bejenariu Andreea Cristina, Popescu Elena Rodica, Gavril Raluca, Gireadă Bogdan, Soroceanu Radu Petru, Gavrilovici Ovidiu, Ștefănescu Cristinel

机构信息

Department of Medicine III, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania.

"Socola" Institute of Psychiatry, 36 Bucium Street, 700282 Iasi, Romania.

出版信息

Biomedicines. 2024 Oct 31;12(11):2501. doi: 10.3390/biomedicines12112501.

Abstract

There are studies that have investigated the association of pro-inflammatory cytokines with depressive disorders, but they often present certain limitations. In this study, two substantial groups of patients were analyzed: 92 patients with major depressive disorder and 76 without depressive disorders. The strict inclusion and exclusion criteria for the analyzed groups significantly increased the value of the obtained results. The research question of this study was whether levels of inflammation, measured by the inflammatory markers IL-6, IL-1α, and TNF-α, could predict the severity of depressive symptoms. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contribute to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL-6, IL-1α) and tumor necrosis factor-alpha (TNF α), have been identified in patients with major depressive disorder compared to the findings in healthy controls. Inflammatory markers (IL-6, IL-1α, and TNF-α) were measured in a sample of 92 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no depression or inflammatory conditions (n = 76). Severity of depressive symptoms was assessed using HAM-D scores. The study results indicated that values of plasma inflammatory markers were significantly higher in patients with major depressive disorder (MDD) compared to the control group (IL-1α: 1.16 ± 0.44 pg/mL vs. 0.89 ± 0.25 pg/mL, = 0.0004; IL-6: 9.21 ± 4.82 pg/mL vs. 7.16 ± 4.32 pg/mL, = 0.0149; and TNF-α: 2.02 ± 0.96 pg/mL vs. 1.67 ± 0.8 pg/mL, = 0.0286). The differences remained significant after applying logarithmic transformation, which was necessary to adjust for outlier values. An analysis of demographic characteristics showed that the frequency of women (67.4% vs. 36.84%, < 0.001), cohabiting individuals (28.26% vs. 10.53%, = 0.0001), and alcohol consumers (67.39% vs. 47.37%, = 0.0087) was significantly higher in patients with MDD. The level of education was significantly lower in patients with MDD (median (IQR): 12 (2.5) years vs. 14 (8) years, = 0.0016). The evaluation of confounding variables, including patients' gender, marital status, education level, and alcohol consumption, was performed using multiple linear regression models. The results indicated that these demographic variables did not significantly influence the correlation between the HAM-D score and the values of IL-6, IL-1α, and TNF-α. A significant correlation between the HAM-D score and the logarithmic values of inflammatory markers was observed for log IL-1α in men (r = 0.355, = 0.0014), log IL-6 in women (r = 0.0313, = 0.0027), and log TNF-α in women (r = 0.3922, = 0.0001). The results of the multiple linear regression and predictive analysis indicated that IL-1α (AUC = 0.677, = 0.0004), IL-6 (AUC = 0.724, < 0.001), and TNF-α (AUC = 0.861, < 0.001) demonstrate high accuracy in discriminating patients with MDD. The results highlighted that IL-6 (AUC = 0.724; 95% CI: 0.648-0.801) and TNF-α (AUC = 0.861; 95% CI: 0.797-0.925) are significant predictors for major depressive disorder. The study highlights the potential of cytokines (IL-1α, IL-6 and TNF-α) as diagnostic markers. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms.

摘要

已有研究对促炎细胞因子与抑郁症之间的关联进行了调查,但这些研究往往存在一定局限性。在本研究中,分析了两组数量可观的患者:92例重度抑郁症患者和76例无抑郁症患者。所分析组别的严格纳入和排除标准显著提高了所得结果的价值。本研究的研究问题是,通过炎症标志物白细胞介素-6(IL-6)、白细胞介素-1α(IL-1α)和肿瘤坏死因子-α(TNF-α)衡量的炎症水平是否能够预测抑郁症状的严重程度。这可以为炎症在抑郁症发病机制中起显著作用这一假说提供额外证据。数据分析支持炎症的生物学机制促成抑郁症临床表现这一假说。与健康对照的结果相比,已确定重度抑郁症患者体内炎症标志物水平升高,尤其是白细胞介素(IL-6、IL-1α)和肿瘤坏死因子-α(TNF-α)。在罗马尼亚雅西的索科拉精神病学研究所住院的92例患者样本中测量了炎症标志物(IL-6、IL-1α和TNF-α),并与无抑郁症或炎症状况的对照组(n = 76)进行比较。使用汉密尔顿抑郁量表(HAM-D)评分评估抑郁症状的严重程度。研究结果表明,与对照组相比,重度抑郁症(MDD)患者的血浆炎症标志物值显著更高(IL-1α:1.16±0.44 pg/mL对0.89±0.25 pg/mL,P = 0.0004;IL-6:9.21±4.82 pg/mL对7.16±4.32 pg/mL,P = 0.0149;TNF-α:2.02±0.96 pg/mL对1.67±0.8 pg/mL,P = 0.0286)。在应用对数转换后差异仍然显著,对数转换对于校正异常值是必要的。人口统计学特征分析表明,MDD患者中女性的比例(67.4%对36.84%,P < 0.001)、同居个体的比例(28.26%对10.53%,P = 0.0001)和饮酒者的比例(67.39%对47.37%,P = 0.0087)显著更高。MDD患者的教育水平显著更低(中位数(四分位间距):12(2.5)年对14(8)年,P = 0.0016)。使用多元线性回归模型对包括患者性别、婚姻状况、教育水平和饮酒情况在内的混杂变量进行评估。结果表明,这些人口统计学变量并未显著影响HAM-D评分与IL-6、IL-1α和TNF-α值之间的相关性。在男性中观察到HAM-D评分与IL-1α的对数值之间存在显著相关性(r = 0.355,P = 0.0014),在女性中观察到HAM-D评分与IL-6的对数值之间存在显著相关性(r = 0.313,P = 0.0027),在女性中观察到HAM-D评分与TNF-α的对数值之间存在显著相关性(r = 0.3922,P = 0.0001)。多元线性回归和预测分析的结果表明,IL-1α(曲线下面积(AUC)= 0.677,P = 0.0004)、IL-6(AUC = 0.724,P < 0.001)和TNF-α(AUC = 0.861,P < 0.001)在区分MDD患者方面表现出高准确性。结果突出表明,IL-6(AUC = 0.724;95%置信区间:0.648 - 0.801)和TNF-α(AUC = 0.861;95%置信区间:0.797 - 0.925)是重度抑郁症的显著预测指标。该研究突出了细胞因子(IL-1α、IL-6和TNF-α)作为诊断标志物的潜力。这些发现支持炎症可能在抑郁症状的发生或加重中起重要作用这一假说。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7afc/11591788/01c53a091519/biomedicines-12-02501-g001.jpg

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