A machine learning approach to predicting clinical trajectories in bipolar disorder

Bipolar disorder (BD) is characterized by significant heterogeneity in clinical presentation, age of onset, and diagnostic delays. Identifying clinical trajectories and subtypes is a central aim of precision psychiatry, with the goal of improving risk stratification and characterization of illness courses, enabling early recognition of high-risk patients and facilitating timely interventions that improve long-term outcomes.

This is a dual-site retrospective cross-sectional secondary analysis of 203 clinical datasets from BD patients to develop machine learning models: Random Forest, Weighted Logistic Regression (LR), and XGBoost, supplemented by statistical modelling, to predict age of onset timing (early/late onset) and illness severity. Survival analysis (Kaplan-Meier and Cox proportional hazards) investigated factors influencing diagnostic delay, while clustering identified patient subtypes.

Single-split Weighted LR (AUC = 0.733) and nested cross-validation XGBoost (AUC = 0.729) achieved superior performance in predicting onset timing. Cluster analysis identified three distinct phenotypes: baseline low complexity, late-onset familial-severe, and an early-onset comorbid group. Survival analysis revealed that the time to diagnosis was independent of clinical risk profiles (Log-Rank p = 0.34), with the most severe cases experiencing significant diagnostic latency.

Machine learning accurately predicts BD clinical trajectories using routinely collected data in an African cohort. Diagnostic delay did not differ significantly across clinical risk or severity strata, indicating that the measured variables did not explain variation in time to diagnosis.