The TOP study - Identification of phenotypes and genetic susceptibility in severe mental disorders

Severe mental disorders (schizophrenia and bipolar/manic-depressive disorder) are major causes of disability worldwide, and rank as some of the most costly disorders to afflict humans. The etiology still remains elusive, but there is now overwhelming evid ence that genetic factors play a prominent role. The search for genetic mechanisms has been problematic because of the lack of valid diagnostic criteria and inadequate genetic methods. However, newly developed brain imaging techniques are potentially eff ective tools for identification of specific phenotypes (endophenotypes), and the sequencing of the human genome as well as new high throughput molecular genetic techniques have opened new and huge possibilities in this field of research. These new method s and approach to psychiatric genetics will be used in this project. The goal is to identify genetic factors that contribute to the development of schizophrenia and bipolar disorder by using endophenotypes based on clinical characteristics, cognitive func tion and brain imaging data. This proposal is based on a close collaboration between all psychiatric hospitals in Oslo and basic research groups through the thematic research area in psychosis. It will build on and extend ongoing clinical and brain imagi ng studies, and the goal is to include 1000 well characterized patients and 400 controls. A subgroup of these patients will be investigated with brain imaging techniques (MRI), and the collected DNA will be analyzed for genetic variants associated with th e endophenoypes as well as the diagnoses. The project will fund patient assessments (clinical and MRI investigations) as well as psychiatric molecular genetic analyses, and high-thoughput FUGE platforms will be used. An agreement for pooling data is made with several international partners. The project will contribute to a better understanding of the pathophysiology of these disorders, which may lead to better prevention and more effective treatment regimens.