Serum cytokines and inflammatory proteins in individuals with heroin use disorder: potential mechanistically based biomarkers for diagnosis.

IF 5.8 1区 医学 Q1 PSYCHIATRY
Eduardo R Butelman, Yuefeng Huang, Flurin Cathomas, Pierre-Olivier Gaudreault, Panos Roussos, Scott J Russo, Rita Z Goldstein, Nelly Alia-Klein
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引用次数: 0

Abstract

Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin use disorder (iHUD) show dysregulated levels of several cytokines in the blood. However, there is limited data on a comprehensive panel of such markers in iHUD versus healthy controls (HC), especially considered as a multi-target biomarker. We used a validated proximity extension assay for the relative quantification of 92 cytokines and inflammatory proteins in the serum of iHUD on medication-assisted therapy (MAT; n = 21), compared to HC (n = 24). Twenty-nine targets showed significant group differences (primarily iHUD>HC), surviving multiple comparison corrections (p = 0.05). These targets included 19 members of canonical cytokine families, including specific chemokines, interleukins, growth factors, and tumor necrosis factor (TNF)-related proteins. For dimensionality reduction, data from these 19 cytokines were entered into a principal component (PC) analysis, with PC1 scores showing significant group differences (iHUD > HC; p < 0.0001). A receiver-operating characteristic (ROC) curve analysis yielded an AUROC = 91.7% (p < 0.0001). This PC1 score remained a positive predictor of being in the HUD group in a multivariable logistic regression, that included select demographic/clinical variables. Overall, this study shows a panel of cytokines that differ significantly between iHUD and HC, providing a multi-target "cytokine biomarker score" for potential diagnostic purposes, and future examination of disease severity.

海洛因使用障碍患者的血清细胞因子和炎症蛋白:用于诊断的潜在机理生物标志物。
阿片类药物使用障碍会导致严重的发病率和死亡率,因此迫切需要新的机理靶点和生物标志物来进行诊断和预后。接触μ阿片受体(MOR)激动剂会导致外周血细胞因子和炎症蛋白网络以及大脑胶质细胞和神经元发生变化。海洛因使用障碍(iHUD)患者血液中多种细胞因子水平失调。然而,有关 iHUD 与健康对照(HC)中此类标记物的综合数据有限,尤其是作为多目标生物标记物。我们使用了一种经过验证的近距离延伸测定法,对接受药物辅助治疗的 iHUD(MAT;n = 21)与健康对照组(n = 24)血清中的 92 种细胞因子和炎症蛋白进行了相对定量。经多重比较校正(P = 0.05),29 个靶标显示出明显的组间差异(主要是 iHUD>HC)。这些靶标包括 19 个典型细胞因子家族成员,包括特异性趋化因子、白细胞介素、生长因子和肿瘤坏死因子 (TNF) 相关蛋白。为了降维,将这 19 种细胞因子的数据输入主成分(PC)分析,PC1 分数显示出显著的组间差异(iHUD > HC; p
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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