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. These investigators have developed a research study focusing on the genetics of atypical antipsychotic induced weight gain (AAP wt gain). More than 50% of patients on AAPs gain >10% of their initial weight, although some gain >40%. This weight gain often results in significant medical morbidity, substantial financial burden, and increased medication non-compliance. Little is known about the underlying mechanism for this weight gain. Identifying risk factors may prevent medical and financial morbidity, disease relapse, and improve overall quality of life (QOL) for patients with schizophrenia. Current research in this area does not take into account genetics, physiology, diet, and physical activity in a controlled manner. Based on pilot data provided by these investigators, they propose a pharmacogenetic study of AAP wt gain in schizophrenia to examine the role of both genetic and physiologic risk factors in the mechanism behind this phenomenon. Specifically, the goals of the study are: 1) to determine the relationship of cytochrome P450 polymorphisms to wieght measures and AAP serum levels. Patients with schizophrenia treated with quetiapine, risperidone, and olanzapine will be recruited and genotyped for CYP 2D6, 1A2, 3A4, 2C9, 2C19, and 2E1; 2) to genotype for polymorphisms of the beta 3 and 5HT receptors to determine the relationship between these polymorphisms and weight measures; 3) to measure serum levels of leptin, insulin, glucose, and homocystine over a year and examine their relationship to weight changes; and 4) to serially measure weight, medication compliance, and QOL in patients receiving AAPs and examine the influence of weight on QOL and medication compliance.
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