Grant: Project Grant

Schizophrenia is a severe mental illness that affects approximately 1% of Canadians, placing considerable burden on individuals with the illness, their families and the health care system. The biological causes that underlie this disorder are not yet fully understood, limiting discovery of new and more effective treatments. Recent genetic advances have revealed that individuals with a specific variation in the gene for complement C4 are at increased risk of developing schizophrenia. While the main function of complement C4 is to activate the immune system in response to infection, recent studies have shown that complement C4 also plays an important role in normal brain development, where it regulates formation of synaptic connections between brain cells. In this study we will characterize alterations in complement C4 in postmortem brain tissue from individuals diagnosed with schizophrenia, and determine whether these alterations might lead to abnormal synaptic connections in this disorder. Our results will provide a greater understanding of the biological mechanisms by which complement C4 increases risk of schizophrenia. In the longer term, our data may provide clues to assist development of novel therapies for treating individuals with this disorder.