Three biomarker-based categories, called biotypes, outperformed traditional diagnoses, such as schizophrenia and bipolar disorder with psychosis, in sorting psychosis cases into distinct subgroups on the basis of brain biology. The biotypes were more biologically homogeneous than categories based on observable symptoms. Just as fever or infection can have many different causes, multiple psychosis-causing disease processes -- operating via different biological pathways -- can lead to similar symptoms and confound the search for improved treatments.