Machine Learning Based on Routine Hematological Parameters and Derived Inflammatory Indices for the Diagnosis of Schizophrenia

Background: Schizophrenia is frequently underdiagnosed or diagnosed late due to the lack of objective diagnostic markers. This study aimed to develop and validate a machine learning model using routine hematological parameters for the auxiliary diagnosis of schizophrenia. Methods: A total of 150 first-episode drug-naïve schizophrenia patients and 150 healthy controls were enrolled. Study parameters included routine hematological parameters and its derived inflammatory markers. Feature selection was performed using Elastic Net regression, followed by the construction of an L2-regularized logistic regression model. Model discriminative performance, calibration, and clinical utility were assessed through internal validation, area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. An independent cohort of 50 schizophrenia patients and 50 patients with major depressive disorder (MDD) was used for exploratory differential diagnostic evaluation. Results: The final model incorporated 12 features: neutrophil count (NEUT), eosinophil count (EO), mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-platelet ratio (NPR), along with age and sex. The model achieved an AUC of 0.859 (95% CI: 0.780–0.937) on the test set, with an accuracy of 0.767, sensitivity of 0.711, and specificity of 0.822. Calibration curves confirmed good calibration, and decision curve analysis further verified its clinical utility. In the exploratory differential diagnostic analysis, the model showed limited performance in distinguishing schizophrenia from MDD. Conclusions: The model based on routine hematological parameters and L2-regularized logistic regression can effectively differentiate first-episode drug-naïve schizophrenia patients from healthy controls, providing a low-cost and easily accessible auxiliary diagnostic tool for clinical practice.