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预测对选择性5-羟色胺再摄取抑制剂(SSRI)的耐药性:基于支持向量机的临床特征和标签单核苷酸多态性(tagSNP)预测模型

Predicting SSRI-Resistance: Clinical Features and tagSNPs Prediction Models Based on Support Vector Machine.

作者信息

Zhang Huijie, Li Xianglu, Pang Jianyue, Zhao Xiaofeng, Cao Suxia, Wang Xinyou, Wang Xingbang, Li Hengfen

机构信息

Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

College of Economics and Management, Zhongyuan University of Technology, Zhengzhou, China.

出版信息

Front Psychiatry. 2020 Jun 3;11:493. doi: 10.3389/fpsyt.2020.00493. eCollection 2020.

Abstract

BACKGROUND

A large proportion of major depressive patients will experience recurring episodes. Many patients still do not response to available antidepressants. In order to meaningfully predict who will not respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables.

METHODS

Eight hundred fifty-seven patients with recurrent major depressive disorder who were followed up 3-10 years involved 32 variables including socio-demographic, clinical features, and SSRIs treatment features when they received the first treatment. Also, 34 tagSNPs related to 5-HT signaling pathway, were detected by using mass spectrometry analysis. The training samples which had 12 clinical variables and four tagSNPs with statistical differences were learned repeatedly to establish prediction models based on support vector machine (SVM).

RESULTS

Twelve clinical features (psychomotor retardation, psychotic symptoms, suicidality, weight loss, SSRIs average dose, first-course treatment response, sleep disturbance, residual symptoms, personality, onset age, frequency of episode, and duration) were found significantly difference () between 302 SSRI-resistance and 304 SSRI non-resistance group. Ten SSRI-resistance predicting models were finally selected by using support vector machine, and our study found that mutations in tagSNPs increased the accuracy of these models to a certain degree.

CONCLUSION

Using a data-driven machine learning method, we found 10 predictive models by mining existing clinical data, which might enable prospective identification of patients who are likely to resistance to SSRIs antidepressant.

摘要

背景

很大一部分重度抑郁症患者会经历复发。许多患者对现有的抗抑郁药仍无反应。为了有意义地预测谁对哪种抗抑郁药无反应,可能需要结合多种生物标志物和临床变量。

方法

857例复发性重度抑郁症患者接受了3至10年的随访,他们在首次治疗时涉及32个变量,包括社会人口统计学、临床特征和选择性5-羟色胺再摄取抑制剂(SSRI)治疗特征。此外,通过质谱分析检测了与5-羟色胺信号通路相关的34个标签单核苷酸多态性(tagSNP)。对具有12个临床变量和4个具有统计学差异的tagSNP的训练样本进行反复学习,以建立基于支持向量机(SVM)的预测模型。

结果

在302例SSRI抵抗组和304例SSRI非抵抗组之间,发现12个临床特征(精神运动迟缓、精神病性症状、自杀倾向、体重减轻、SSRI平均剂量、首次疗程治疗反应、睡眠障碍、残留症状、人格、发病年龄、发作频率和病程)存在显著差异()。最终使用支持向量机选择了10个SSRI抵抗预测模型,我们的研究发现tagSNP中的突变在一定程度上提高了这些模型的准确性。

结论

使用数据驱动的机器学习方法,我们通过挖掘现有临床数据发现了10个预测模型,这可能有助于前瞻性地识别可能对SSRI抗抑郁药耐药的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb1a/7283444/ccabfcefbf1a/fpsyt-11-00493-g001.jpg

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