Grant: Operating Grant

Schizophrenia is a severe, chronic, and debilitating mental disorder. It affects 1 of every 100 Canadians. The disease impacts a vast array of brain systems, seriously affecting a person's thoughts, feelings, and ability to function. Researchers have worked for decades to understand the biological pathways involved in schizophrenia and identify the root causes of the disorder. Over time, research provided evidence supporting the "dopamine D2 receptor hypothesis." This theory contends that there is an association between an impaired striatal dopaminergic neurotransmission and schizophrenia. In support of this theory, many studies found a positive correlation between the D2 binding affinity and effectiveness of anti-psychotic drugs. Additionally, mutation in a gene, called Disrupted-in-schizophrenia-1 (DISC1), recently emerged as a potential key. This genetic mutation appears to increase risk of schizophrenia. However, the specific biological mechanisms that increase risk are not understood. Detailed investigation of these biological mechanisms is an important priority. By investigating the role of DISC1 in the regulation of D2 receptor signaling, the project will: 1. Reveal molecular mechanisms underlying which DISC1 may modulate D2 receptor-mediated functions. 2. Provide a molecular framework in which to view DISC1 and D2 receptor interaction. 3. Provide a potential therapeutic target for the development of novel antipsychotics. Abnormalities in the communication between these two proteins may underlie psychiatric diseases such as schizophrenia. This project aims to provide a new avenue to identify specific targets for therapeutics to modulate dopamine deficit diseases and thereby improve health outcomes for Canadians suffering from schizophrenia as well as other conditions which involve this biological mechanism.