Grant: CIHR Clinician Scientist - Phase 2

Schizophrenia is a chronic mental illness that usually begins in early adulthood, with symptoms like hearing voices (auditory hallucinations) and believing that people are conspiring against you or controlling your thoughts (paranoid delusions). Most scientists agree that schizophrenia results from abnormal brain development that produces subtle changes in the way in which some neurons are arranged and located. Recently, genetic studies have identified a number of strong candidate genes that likely increase the risk of getting schizophrenia or cause the illness in a subset of patients. One of these genes, DISC1, plays a role in controlling the migration of neurons to their proper locations as the brain develops. However, no one knows for sure whether mutations or variations in this gene can actually cause the abnormalities seen in the brains of patients with schizophrenia. We propose several experiments to see if alterations in the DISC1 gene in mice produces the same kind of abnormalities seen in human schizophrenia brains, and how these genetic changes affect the way in which individual neurons move. These experiments will show for the first time how a gene implicated in mental illness can disrupt brain development, and this knowledge will form the basis to develop new treatments targeted at this mechanism. Currently, all treatments for schizophrenia address only the symptoms, not the cause, and real progress in improving patient care will depend on more specific treatments based on understanding disease mechanisms.