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Phenotypic heterogeneity within patients and controls may explain why the genetic variants contributing to schizophrenia risk explain only a fraction of the heritability. The aim of this study is to investigate quantitative and qualitative differences in psychosis symptoms in a sample including psychosis patients, their relatives, and community controls. We combined factor analysis and latent class analysis to analyze variation in Comprehensive Assessment of Symptoms and History lifetime-rated symptoms in 4286 subjects. The Wechsler Adult Intelligence Scale-Intelligence Quotient (N = 2663) and the Camberwell Assessment of Need rating scale (N = 625) were assessed in a subsample. Variation in 5 continuous dimensions (disorganization, positive, negative, mania, and depression) was accounted for by the presence of 7 homogeneous classes (Kraepelinian schizophrenia, affective psychosis, manic-depression, deficit nonpsychosis, depression, healthy, and no symptoms). Eighty-five percent of the schizophrenia patients was assigned to the Kraepelinian schizophrenia class (characterized by high scores on the 5 dimensions, low IQ, and poor outcome) while 15% was assigned to the affective psychosis class (relatively low disorganization and negative scores, normal IQ, and good outcome). In bipolar patients (91% bipolar I), 41% was assigned to the Kraepelinian schizophrenia class, 44% to the affective psychosis class, and 10% to the manic-depression class. Latent class membership was associated with intelligence in psychosis patients and in their relatives but not in community controls. In conclusion, symptom heterogeneity is more pronounced in bipolar disorder compared with schizophrenia. Reducing phenotypic heterogeneity within psychosis patients and controls may facilitate etiological research.

Kraepelin Was Right: A Latent Class Analysis of Symptom Dimensions in Patients and Controls