Explainable and externally validated machine learning for neuropsychiatric diagnosis via electrocardiograms

Electrocardiogram (ECG) analysis has emerged as a promising tool for identifying physiological changes associated with neuropsychiatric conditions. The relationship between cardiovascular health and neuropsychiatric disorders suggests that ECG abnormalities could serve as valuable biomarkers for more efficient detection, therapy monitoring, and risk stratification. However, the potential of the ECG to accurately distinguish neuropsychiatric conditions, particularly among diverse patient populations, remains underexplored. This study utilized ECG markers and basic demographic data to predict neuropsychiatric conditions using machine learning models, with targets defined through ICD-10 codes. Both internal and external validation were performed using the MIMIC-IV and ECG-View datasets respectively. Performance was assessed using AUROC scores. To enhance model interpretability, Shapley values were applied to provide insights into the contributions of individual ECG features to the predictions. Significant predictive performance was observed for conditions within the neurological and psychiatric groups. For the neurological group, Alzheimer's disease (G30) achieved an internal AUROC of 0.813 (0.812-0.814) and an external AUROC of 0.868 (0.867-0.868). In the psychiatric group, unspecified dementia (F03) showed an internal AUROC of 0.849 (0.848-0.849) and an external AUROC of 0.862 (0.861-0.863). Discriminative features align with known ECG markers but also provide hints on potentially new markers. ECG offers significant promise for diagnosing and monitoring neuropsychiatric conditions, with robust predictive performance across internal and external cohorts. Future work should focus on addressing potential confounders, such as therapy-related cardiotoxicity, and expanding the scope of ECG applications, including personalized care and early intervention strategies.