Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning

Abstract Cognitive impairments are generally observed in patients with schizophrenia. However, it is unclear whether neurocognitive dysfunction can predict the efficacy of antipsychotics for first-episode schizophrenia (FES). Machine learning methods provide a relatively unbiased approach when evalu...

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Main Authors: Xianghe Wang, Tianqi Gao, Xiaodong Guo, Bingjie Huang, Yunfei Ji, Wanheng Hu, Xiaolin Yin, Yue Zheng, Chengcheng Pu, Xin Yu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Schizophrenia
Online Access:https://doi.org/10.1038/s41537-025-00640-y
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author Xianghe Wang
Tianqi Gao
Xiaodong Guo
Bingjie Huang
Yunfei Ji
Wanheng Hu
Xiaolin Yin
Yue Zheng
Chengcheng Pu
Xin Yu
author_facet Xianghe Wang
Tianqi Gao
Xiaodong Guo
Bingjie Huang
Yunfei Ji
Wanheng Hu
Xiaolin Yin
Yue Zheng
Chengcheng Pu
Xin Yu
author_sort Xianghe Wang
collection DOAJ
description Abstract Cognitive impairments are generally observed in patients with schizophrenia. However, it is unclear whether neurocognitive dysfunction can predict the efficacy of antipsychotics for first-episode schizophrenia (FES). Machine learning methods provide a relatively unbiased approach when evaluating heterogeneous data, especially when building multifactor prediction models. This study conducted a secondary analysis based on the Chinese FES Trial (CNFEST), which was a 1-year study involving a randomized controlled trial for the first eight weeks followed by a 48-week open-label observation. The current study aimed to build a prediction model of eight-week antipsychotic response based on baseline clinical and demographic features. Six machine learning algorithms, including random forest, eXtreme gradient boosting (XGBoost), logistic regression, linear support vector machine (SVM), radial basis function SVM and poly SVM were applied and compared to draw the prediction model. The predictive effects were evaluated by balanced accuracy, sensitivity and specificity. The predictive factors were compared with F scores. A total of 450 qualified subjects contributed to the model. The prediction model constructed via XGBoost algorithm had the highest accuracy (68.8%) and prognostic certainty (44.3%) among all the algorithms. The baseline neurocognitive tests with strong predictive significance were the Grooved Pegboard Test, Trail Making Test Part A, Paced Auditory Serial Addition Test, Brief Visuospatial Learning Test, Hopkins Verbal Learning Test and Color Trails Test. This study emphasizes the importance of fine motor skills, verbal learning, visual learning, working memory and attention for the response of drug-naïve FES patients to antipsychotics. The model generated by XGBoost, which shows preferable accuracy, provides psychiatric practitioners with a possible way to predict efficacy for FES patients.
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language English
publishDate 2025-07-01
publisher Nature Portfolio
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series Schizophrenia
spelling doaj-art-3b666bd901b44bcdac9cd5bf0076d73a2025-08-20T04:02:56ZengNature PortfolioSchizophrenia2754-69932025-07-011111910.1038/s41537-025-00640-yNeurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learningXianghe Wang0Tianqi Gao1Xiaodong Guo2Bingjie Huang3Yunfei Ji4Wanheng Hu5Xiaolin Yin6Yue Zheng7Chengcheng Pu8Xin Yu9Peking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalPeking University Sixth HospitalAbstract Cognitive impairments are generally observed in patients with schizophrenia. However, it is unclear whether neurocognitive dysfunction can predict the efficacy of antipsychotics for first-episode schizophrenia (FES). Machine learning methods provide a relatively unbiased approach when evaluating heterogeneous data, especially when building multifactor prediction models. This study conducted a secondary analysis based on the Chinese FES Trial (CNFEST), which was a 1-year study involving a randomized controlled trial for the first eight weeks followed by a 48-week open-label observation. The current study aimed to build a prediction model of eight-week antipsychotic response based on baseline clinical and demographic features. Six machine learning algorithms, including random forest, eXtreme gradient boosting (XGBoost), logistic regression, linear support vector machine (SVM), radial basis function SVM and poly SVM were applied and compared to draw the prediction model. The predictive effects were evaluated by balanced accuracy, sensitivity and specificity. The predictive factors were compared with F scores. A total of 450 qualified subjects contributed to the model. The prediction model constructed via XGBoost algorithm had the highest accuracy (68.8%) and prognostic certainty (44.3%) among all the algorithms. The baseline neurocognitive tests with strong predictive significance were the Grooved Pegboard Test, Trail Making Test Part A, Paced Auditory Serial Addition Test, Brief Visuospatial Learning Test, Hopkins Verbal Learning Test and Color Trails Test. This study emphasizes the importance of fine motor skills, verbal learning, visual learning, working memory and attention for the response of drug-naïve FES patients to antipsychotics. The model generated by XGBoost, which shows preferable accuracy, provides psychiatric practitioners with a possible way to predict efficacy for FES patients.https://doi.org/10.1038/s41537-025-00640-y
spellingShingle Xianghe Wang
Tianqi Gao
Xiaodong Guo
Bingjie Huang
Yunfei Ji
Wanheng Hu
Xiaolin Yin
Yue Zheng
Chengcheng Pu
Xin Yu
Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
Schizophrenia
title Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
title_full Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
title_fullStr Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
title_full_unstemmed Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
title_short Neurocognition as a major predictor of 8-week response to antipsychotics for drug-naïve first-episode schizophrenia using machine learning
title_sort neurocognition as a major predictor of 8 week response to antipsychotics for drug naive first episode schizophrenia using machine learning
url https://doi.org/10.1038/s41537-025-00640-y
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