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利用欧盟多国基因与环境研究(EU-GEI)病例对照研究及现代统计学习方法开发并验证首次发作精神病诊断预测模型

Development and Validation of Predictive Model for a Diagnosis of First Episode Psychosis Using the Multinational EU-GEI Case-control Study and Modern Statistical Learning Methods.

作者信息

Ajnakina Olesya, Fadilah Ihsan, Quattrone Diego, Arango Celso, Berardi Domenico, Bernardo Miguel, Bobes Julio, de Haan Lieuwe, Del-Ben Cristina Marta, Gayer-Anderson Charlotte, Stilo Simona, Jongsma Hannah E, Lasalvia Antonio, Tosato Sarah, Llorca Pierre-Michel, Menezes Paulo Rossi, Rutten Bart P, Santos Jose Luis, Sanjuán Julio, Selten Jean-Paul, Szöke Andrei, Tarricone Ilaria, D'Andrea Giuseppe, Tortelli Andrea, Velthorst Eva, Jones Peter B, Romero Manuel Arrojo, La Cascia Caterina, Kirkbride James B, van Os Jim, O'Donovan Michael, Morgan Craig, di Forti Marta, Murray Robin M, Stahl Daniel

机构信息

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, University of London, London, UK.

Department of Behavioural Science and Health, Institute of Epidemiology and Health Care, University College London, London, UK.

出版信息

Schizophr Bull Open. 2023 Mar 10;4(1):sgad008. doi: 10.1093/schizbullopen/sgad008. eCollection 2023 Jan.

Abstract

BACKGROUND AND HYPOTHESIS

It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries.

STUDY DESIGN

We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity.

STUDY RESULTS

Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (ranges = 0.84-0.86). Specificity (range = 73.9-78.0%) and sensitivity (range = 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands.

CONCLUSIONS

The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.

摘要

背景与假设

有人认为,诊断模型的可用性将有助于更快地识别首次发作精神病(FEP)风险较高的个体。因此,我们开发、评估并验证了一种诊断风险估计模型,用于对六个国家的FEP个体和对照进行分类。

研究设计

我们使用了一项大型多中心研究的数据,该研究涵盖了从六个国家的17个研究地点招募的2627名表型明确的参与者(年龄在18 - 64岁之间),这是欧洲国家精神分裂症网络研究基因 - 环境相互作用研究网络的一部分。为了构建诊断模型并确定估计个体FEP风险的重要因素,我们应用了带有最小绝对收缩和选择算子正则化的二元逻辑模型。该模型采用内部 - 外部交叉验证方法进行验证。模型性能通过受试者操作特征曲线下面积(AUROC)、校准、敏感性和特异性进行评估。

研究结果

纳入预先选择的22个预测变量后,该模型能够在所有六个国家中以高精度区分患有FEP的成年人和对照(范围 = 0.84 - 0.86)。特异性(范围 = 73.9 - 78.0%)和敏感性(范围 = 75.6 - 79.3%)同样良好,累积表明模型准确性极佳;不过,当专门应用于来自法国、英国和荷兰的参与者时,诊断模型的校准斜率显示存在一些过拟合。

结论

新的FEP模型在六个具有不同种族构成的国家中实现了良好的区分度和校准,支持了其稳健性和良好的通用性。

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