This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This application is a request for competitive renewal or our research on the diagnosis and phenomenology of schizophrenia. The work aims to understand the phenomenology of schizophrenia in terms of its underlying mechanisms, refine our definition of its phenotype, and describe the lifelong trajectory of the illness and its long-term outcome. Since the disorder is characterized by a prolonged lifetime course, longitudinal study of informative cohorts is one of the most powerful strategies for understanding its mechanisms and defining its phenotype. This project seeks to refine the definition of the phenotype of schizophrenia by examining the predictive validity of two different competing models in a large sample of first episode and recent onset patients who are followed longitudinally at multiple time points. One approach, a tridimensional model that defines the phenotype using three symptom clusters (psychoticism, disorganization, and negative symptoms) is currently widely accepted an d studied. The second approach proposes a new unitary model of schizophrenia as defined at the systems level by a fundamental cognitive deficit (""""""""cognitive dysmetria"""""""") and at the neural level by an abnormality in cortical-cerebellar-thalamic-cerebellar circuitry (CCTCC). The predictive validity of these two models will be compared using four validators derived from the evaluation of long-term course: clinical outcome psychosocial outcome, cognition, and brain morphology.
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