A study of children and adolescents with very early onset by age 12 (COS) of DSM-III-R defined schizophrenia is examining the clinical, neurobiological, early neurodevelopmental, genetic, and clinical drug response characteristics of these cases, under Protocols 97-M-0126 and 03-M-0035. Earlier studies have documented the continuity between COS and adult-onset cases. The focus has now shifted to increasing the sample size and evaluation of familial risk factors including: psychiatric diagnoses of family members; neuropsychological testing, anatomic and functional brain imaging, and obtaining blood and fibroblasts for cell lines for genetic studies.