Grant: Project Grant

Severe mental disorders such as schizophrenia or bipolar disorder affect more than 2% of the Canadian population, especially youth. Atypical antipsychotics (AAPs) are the first-line medications for treating these diseases, while they are often associated with severe metabolic side-effects (insulin resistance and diabetes) and heart disease. Increasing evidence is accumulating that metabolic abnormalities play a crucial role in the development of heart disease. Thus, studying the molecular mechanisms through which AAPs induce metabolic dysfunction and their effects on heart metabolism are essential to understanding the development of heart disease following AAP treatment. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory factor, well known to be involved in inflammation and also to play a role in regulating metabolism. Our preliminary data indicate that schizophrenic patients following treatments of AAPs for 2 months have increased plasma MIF. MIF plays a crucial role in the development of metabolic dysfunction induced by a classical AAP, olanzapine. Thus, we will use olanzapine as a representative atypical drug to explore the possible mechanisms of MIF in AAP induced metabolic dysfunction. Our research will include multiple techniques related to basic medicine and molecular biology. I hope to develop a novel strategy to inhibit metabolic side effects and heart disease during atypical antipsychotic treatment. We believe that MIF inhibitors will improve the clinical psychiatric treatment with atypical antipsychotics. Based on the results of these experiments, in our future studies, we are planning to extend the use of MIF inhibitors to clinical practice by collaborating with Dr. Donghong Cui in Shanghai Mental Health Center, China. We would then explore the pharmaceutical possibility of making a combined MIF inhibitor and AAP therapy.