Project Summary

Ofer Agid, M.D. (Young Investigator 2005) of Centre for Addiction and Mental Health/University of Toronto, will employ brain imaging of patients taking certain antipsychotics to study the drugs’ effect on the extrastriatal dopamine D2 receptor system, a different pathway than usually analyzed. Blockage of dopamine D2 receptors is a common feature of antipsychotic action, Dr. Agid explains, but which D2 system stimulates response remains unknown. While most imaging research focuses on striatal D2 receptors, Dr. Agid believes extrastriatal D2 receptors may be more important contributors to mental illness. Dr. Agid hopes to examine the relationship between antipsychotic response and extrastriatal receptors through the first double-blind, randomized, controlled clinical-imaging study in patients taking antipsychotics for their first episode of psychosis. Subjects will start on an atypical antipsychotic (olanzapine) and be randomized to high and standard doses. Clinical condition will be assessed using rating instruments weekly for four weeks. At the end of this period, PET scanning will then map out striatal and extrastriatal D2 receptor activity. If the extrastriatal receptors bear a closer relationship to response, the finding should stimulate the search for drugs that can achieve region-specific targeting of receptors.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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