Grant: Michael Smith New Investigator Award - Schizophrenia

Recent evidence suggests that the symptoms of schizophrenia may arise from dysfunction of the nerve fibres that connect different brain regions together. However, exactly how this might occur at the microscopic level is not clear. Oligodendrocytes are brain cells that produce a fatty insulating substance called myelin, which surrounds nerve fibres and speeds up the transmission of nerve impulses between brain regions. We suggest that the number of oligodendrocytes is lower in individuals with schizophrenia then in healthy people. We believe that this may result from genetic or environmental events that take place during brain development. Having fewer oligodendrocytes would lead to lower levels of myelin surrounding nerve fibres and accordingly faulty transmission of nerve impulses between brain regions. In this study we intend to use post-mortem samples to compare the number of oligodendrocyte cells in the brains of individuals with schizophrenia against that in healthy subjects. We will also measure levels of proteins and fats found in myelin to test if less myelin is present in individuals with schizophrenia. We will then compare the levels of N-acetylaspartate, a molecule that is an indicator of how well axons are working, between the two groups. Finally, we plan to test if antipsychotic drugs are causing changes in the schizophrenia samples by giving these drugs to rats. Identifying abnormalities in nerve fibre connections could offer clues as to the causes of schizophrenia and may provide us with targets for new drugs.