Subtyping first-episode psychosis based on longitudinal symptom trajectories using machine learning

Clinical course after first episode psychosis (FEP) is heterogeneous. Subgrouping and predicting longitudinal symptom trajectories after FEP may help develop personalized treatment approaches. We utilized k-means clustering to identify clusters of 411 FEP patients based on longitudinal positive and negative symptoms. Three clusters were identified. Cluster 1 exhibits lower positive and negative symptoms (LS), lower antipsychotic dose, and relatively higher affective psychosis; Cluster 2 shows lower positive symptoms, persistent negative symptoms (LPPN), and intermediate antipsychotic doses; Cluster 3 presents persistently high levels of both positive and negative symptoms (PPNS), and higher antipsychotic doses. We predicted cluster membership (AUC of 0.74) using ridge logistic regression on baseline data. Key predictors included lower levels of apathy, affective flattening, and anhedonia/asociality in the LS cluster, compared to the LPPN cluster. Hallucination severity, positive thought disorder and manic hostility predicted PPNS. These results help parse the FEP trajectory heterogeneity and may facilitate the development of personalized treatments.