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用于检测抑郁症的免疫-神经内分泌生物标志物组合的鉴定:一种联合效应统计方法。

Identification of an Immune-Neuroendocrine Biomarker Panel for Detection of Depression: A Joint Effects Statistical Approach.

作者信息

Chan Man K, Cooper Jason D, Bot Mariska, Steiner Johann, Penninx Brenda W J H, Bahn Sabine

机构信息

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.

出版信息

Neuroendocrinology. 2016;103(6):693-710. doi: 10.1159/000442208. Epub 2015 Nov 19.

Abstract

BACKGROUND/AIMS: Less than half of depression patients are correctly diagnosed within the primary care setting. Previous proteomic studies have identified numerous immune and neuroendocrine changes in patients. However, few studies have considered the joint effects of biological molecules and their diagnostic potential. Our aim was to develop and validate a diagnostic serum biomarker panel identified through joint effects analysis of multiplex immunoassay profiling data from 1,007 clinical samples.

METHODS

In stage 1, we conducted a meta-analysis of two independent cohorts of 78 first-/recent-onset drug-naive/drug-free depression patients and 156 controls and applied the 10-fold cross-validation with least absolute shrinkage and selection operator regression to identify an optimal diagnostic prediction model (biomarker panel). In stage 2, we tested the discriminatory performance of this biomarker panel using the naturalistic Netherlands Study of Depression and Anxiety (NESDA) cohort of 468 depression patients and 305 controls.

RESULTS

An optimal panel of 33 immune-neuroendocrine biomarkers and gender was selected in the meta-analysis. Testing this biomarker-gender panel using the NESDA cohort resulted in a moderate to good performance to differentiate patients from controls (0.69 < AUC < 0.86), particularly the first-episode patients free of chronic non-psychiatric diseases or medications and following incorporation of sociodemographic covariates (0.76 < AUC < 0.92).

CONCLUSION

Despite the need for additional validation studies, we demonstrated that a blood-based biomarker-sociodemographic panel can detect depression in naturalistic healthcare settings with good discriminatory power. Further refinements of blood biomarker panels aiding in the diagnosis of depression may provide a cost-effective means to increase accuracy of clinical diagnosis within the primary care setting.

摘要

背景/目的:在初级医疗环境中,不到一半的抑郁症患者能得到正确诊断。以往的蛋白质组学研究已确定患者存在众多免疫和神经内分泌变化。然而,很少有研究考虑生物分子的联合作用及其诊断潜力。我们的目的是开发并验证一个诊断血清生物标志物组合,该组合是通过对1007份临床样本的多重免疫分析数据进行联合效应分析确定的。

方法

在第一阶段,我们对两个独立队列进行了荟萃分析,一个队列有78例首发/近期发病、未使用过药物/未服用药物的抑郁症患者,另一个队列有156例对照,并应用具有最小绝对收缩和选择算子回归的10倍交叉验证来确定一个最佳诊断预测模型(生物标志物组合)。在第二阶段,我们使用荷兰抑郁症和焦虑症自然主义研究(NESDA)队列中的468例抑郁症患者和305例对照来测试该生物标志物组合的鉴别性能。

结果

在荟萃分析中选择了一个由33种免疫-神经内分泌生物标志物和性别组成的最佳组合。使用NESDA队列测试该生物标志物-性别组合,结果显示其在区分患者和对照方面具有中等至良好的性能(0.69 < AUC < 0.86),特别是对于没有慢性非精神疾病或药物治疗的首发患者,纳入社会人口统计学协变量后性能更佳(0.76 < AUC < 0.92)。

结论

尽管需要更多的验证研究,但我们证明了基于血液的生物标志物-社会人口统计学组合能够在自然主义医疗环境中以良好的鉴别能力检测出抑郁症。进一步优化有助于抑郁症诊断的血液生物标志物组合可能为提高初级医疗环境中临床诊断的准确性提供一种经济有效的方法。

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