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An accurate predictive model for depressive symptoms in patients with primary Sjögren’s disease based on machine learning algorithms
L. Yang1, Y. Tong2, Y. Jin3, X. Wang4, Y. Yan5, W. Lu6, D. Su7, J. Zou8, K. Huang9
- Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing; and Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing; and Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing; and Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing; and Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. sudinglei@njmu.edu.cn
- Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing; and Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China. zoujianjun100@126.com
- Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing; and Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China. kzhuang@nju.edu.cn
CER19235
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PMID: 41328611 [PubMed]
Received: 14/08/2025
Accepted : 13/11/2025
In Press: 25/11/2025
Abstract
OBJECTIVES:
To develop and validate a machine-learning (ML) model that flags primary Sjögren’s disease (pSjD) patients at high risk of depressive symptoms for earlier clinical attention.
METHODS:
We retrospectively studied 147 pSjD patients (Nanjing First Hospital, 2019-2022). Depressive symptoms were screened with Patient Health Questionnaire-9 (PHQ-9); PHQ-9 ≥5 was the primary endpoint. Missing data were handled by multiple imputation. Data were split 70/30 for training/testing. After univariate screening and LASSO selection, eight ML algorithms (e.g., logistic regression, support vector machine (SVM), tree/boosting methods) were trained with stratified 10-fold cross-validation. Performance was summarised by AUROC/AUPRC, accuracy, precision/recall, Brier score, and calibration; SHAP provided model explainability.
RESULTS:
Four routinely available predictors were retained: fatigue frequency, sleep duration, lymphocyte count, and anti-Ro52 status. Across repeated cross-validation, SVM showed the best overall discrimination (mean AUROC≈0.90) with strong precision and accuracy. In the held-out test set, SVM maintained high performance (AUROC=0.929; AUPRC=0.959; Brier=0.106). SHAP confirmed predictor importance, indicating higher risk with shorter sleep, lower lymphocyte counts, greater fatigue frequency, and anti-Ro52 positivity.
CONCLUSIONS:
This study presents the first ML-based model for predicting depressive symptoms in pSjD patients, highlighting the significance of immuno-inflammatory and clinical factors in depression pathogenesis. The SVM model offers a robust, non-invasive tool for early identification of high-risk individuals, enabling timely and personalised interventions. However, this single-centre, retrospective design with a modest sample limits generalisability; therefore, independent multi-centre validation is required before clinical use.
