Grant: CIHR Fellowship

Antipsychotics are used to treat schizophrenia and other mental illnesses, but antipsychotics cause insulin resistance and increase the risk of type 2 diabetes. Historically, it was thought that blood sugars were regulated by the key hormone insulin through effects in the periphery. We now know that insulin also has an important role in the brain to regulate whole body glucose levels and metabolism. We have shown that antipsychotics can inhibit the central effects of insulin and cause defects in whole body glucose metabolism. Insulin also acts in a brain region called the hippocampus to help with memory and cognition. People with schizophrenia have cognitive dysfunction, and antipsychotics fail to improve this critical aspect of the illness. To help understand why antipsychotics do not improve cognition, we want to examine whether olanzapine, a widely used antipsychotic, prevents insulin in the hippocampus of rats from enhancing cognition. We also want to know if there is a way to alleviate this problem. We will do this by testing if two antidiabetic medications co-administered with olanzapine can restore insulin function in improving cognition and memory. If we see promising results in rodents, we can conduct similar experiments in humans using insulin nasal. Our objective is to investigate how antipsychotics impact insulin pathways in the brain, so that we can use current antidiabetic treatments, or find new ones (using new technologies that use software tools to understand biological data, called "bioinformatics"), to help improve cognition and ultimately better outcomes for patients suffering from schizophrenia.