This application is a request for a competitive renewal of our research on the diagnosis and phenomenology of schizophrenia. To our knowledge, this is the largest ongoing study of first-episode schizophrenia in existence. This study is currently following 293 first-episode patients, some of whom have been followed for as long as 15 years. The study emphasizes understanding the phenomenology of schizophrenia by examining the lifetime trajectory of the illness and its long-term outcome. Since the disorder is characterized by a prolonged lifetime course, longitudinal study of a large group of informative patients is one of the most powerful strategies for examining measures that will illuminate its mechanisms or refine the definition of its phenotype. This study examines 4 domains of variables: Symptoms, psychosocial function, brain morphology as measured by morphometric magnetic resonance imaging, and cognition as measured by both standard neuropsychological tests and a group of experimental tests. We have found that, although symptoms stabilize relatively quickly after initial onset in the majority of patients, the other domains tend to worsen throughout the first decade after onset. This suggests that the disorder may have a worse prognosis, despite adequate treatment, than originally anticipated. We also will divide the patients into groups based levels of recovery and determine the predictors of recovery group. In order to understand the long-term outcome of schizophrenia at the clinical, neural, and cognitive levels, it is important that we continue to study this large group of patients longitudinally on into the second decade of the illness so that we can examine the interrelationships between these four domains and determine whether the downward trends persist or stabilize.
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