Searching for valid psychiatric phenotypes: discrete latent variable models

INTRODUCTION: A primary challenge in psychiatric genetics is the lack of a completely validated system of classification for mental disorders. Appropriate statistical methods are needed to empirically derive more homogenous disorder subtypes. METHODS: Using the framework of Robins and Guze's ('Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia', American Journal of Psychiatry, 1970, 126(7), 983-987) five phases, latent variable models to derive and validate diagnostic groups are described. A process of iterative validation is proposed through which refined phenotypes would facilitate research on genetics, pathogenesis, and treatment, which would in turn aid further refinement of disorder definitions. CONCLUSIONS: Latent variable methods are useful tools for defining and validating psychiatric phenotypes. Further methodological research should address sample size issues and application to iterative validation.