Schizophrenia, the most serious of the mental disorders, afflicts 1% of the population, causing suffering to patients and their families and stretching health care resources to a maximum. It is the mission of Gabriel Pharma to improve the treatment and health care for patients with mental illnesses through genetic, pharmacological and other technologies. A primary goal of this grant is to establish a genetic screen for antipsychotic drug response and genetic predictors of outcome of schizophrenia, enabling an individualized approach to treatment and resource allocation. This proposal describes the rationale, design and scientific development of the Interactive Clinical Information and DNA database (CI-DNA) introduced in Phase I. The CI-Database will be expanded to include two pharmacological database components designed for pharmacogenetics analysis and a first-of-its-kind clinical outcome database for schizophrenia designed for genetic predictor analysis. Phase I successfully developed the clinical portion of a database for the pharmacogenetics of clozapine. As part of the Phase I feasibility study Gabriel Pharma established, for the first time, genetic predictors of negative symptom response to clozapine. In Phase II, subjects in the expanded database will be genotyped for a panel of ten functional candidate gene variants. These genes are chosen for their relationship to the central nervous system (CNS), schizophrenia and antipsychotic drug mechanisms. In addition, three recently discovered schizophrenia susceptibility genes will be examined in the database. The fully developed proprietary CI-DNA database system is a unique innovation enabling the establishment of genetic screens for antipsychotic drug response and schizophrenia outcome through internal and collaborative scientific efforts. This work has the potential of impacting the individual patient with schizophrenia as well as broader needs in related health care delivery. ? ?
