Deficit psychopathology and a paradigm shift in schizophrenia research.

Despite recognition that schizophrenia must have syndrome status in the absence of proof of a single etiopathophysiologic process, a century of work has been based on designs that conceptualize schizophrenia as a single disease entity. Reducing heterogeneity at several levels of functioning is desirable. In this article we summarize progress using deficit syndrome psychopathology to address heterogeneity. The deficit syndrome has proven to be reliable, with construct validity, as well as predictive validity with biological, treatment, and course variables. We propose a shift in schizophrenia research away from the syndrome level toward study designs that identify more homogeneous entities. Doing so will increase the statistical power of study designs by reducing false positive cases.