COATS: Comparison of Optimal Antipsychotic Treatments for Schizophrenia Abstract: Using innovative, preemptive approaches to prevent and manage adverse effects, this study compares aripiprazole, perphenazine, and olanzapine in the treatment of patients who are in the early years of schizophrenia or schizoaffective disorder and who have had a recent exacerbation of their illness. The goal is to optimize clinical outcomes by minimizing adverse effects, by preemptively managing known adverse reactions to these medications. Sixty patients who are within 5 years of their first hospitalization for schizophrenia will be randomized to up to 6 months of open-label treatment with olanzapine, perphenazine, or aripiprazole. Psychopathology ratings will be done blind to treatment assignment. There will be monitoring for and management of weight gain, insulin resistance, cholesterol elevation, and extrapyramidal side effects (EPSE) using pre-determined and consistent strategies. Unmanageable and troubling levels of these adverse outcomes that cannot be attenuated by the pre-determined strategies will be considered outcome failures. Because this is a pilot study, the specific aims reflect efforts to establish feasibility for a larger, definitive study. METS: Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia Abstract: Life expectancy for individuals with schizophrenia is up to 25 years shorter than for the general population. Weight gain and metabolic abnormalities that are associated with morbidity and mortality are common in schizophrenia and have been linked with several antipsychotic medications. However, the most appropriate strategies to ameliorate the risks of weight gain and metabolic abnormalities have not been established. One innovative approach, adjunctive treatment with metformin, has shown promising results in randomized studies of patients early in the course of psychotic illnesses, but this approach has not been systematically tested on a large scale among individuals with chronic schizophrenia or schizoaffective disorder. This study will enroll 140 individuals with schizophrenia or schizoaffective disorder who have a BMI &#8805;27 and are treated with one or a combination of two antipsychotic medications. Participants will be randomized to augmentation treatment with metformin or placebo. All participants will receive a manualized behavioral intervention aimed at reducing their risk of cardiovascular disease. The study began as a pilot study, but because it was so feasible and important, it was expanded to include a larger sample size for a full efficacy study. Thus the specific aims include both feasibility outcomes (Aims 1-3) as well as substantive outcome goals (Aims 4-5). CRSTN: Cognitive Remediation on the Schizophrenia Trials Network Abstract: This study will determine the feasibility of implementing a cognitive remediation program in a network of sites that do not specialize in this area of research, and will help determine the feasibility of multi-site cognitive remediation projects as an intervention in itself and as a platform for pharmacologic cognitive enhancement trials. Forty eight (48) patients with schizophrenia or schizoaffective disorder will be randomly assigned to 8 - 12 weeks of a cognitive remediation program or a control program consisting of video games. Because this is a pilot study, the specific aims reflect efforts to establish feasibility for a larger, definitive study.