We have recently demonstrated the capacity to label dopamine-2 receptors in human volunteers using 11C-N-Methylspiperone positron emission tomography. To date, utilize a population of normal volunteers, we have demonstrated its safety and efficacy in labeling a sub-population of dopamine receptors. Because the dopamine system has been strongly implicated in the pathogenesis of schizophrenic disorders and of tardive dyskinesia, it is important that this new technology be applied to patients with these disorders to investigate for the possibility of dopamine receptor abnormalities. We, therefore, propose to collect a cohort of drug naive schizophrenic patients over the next three years. By diligently attempting to collect patients who have never been exposed to neuroleptic medications, we will be able to investigate for dopamine receptor abnormalities without the confounding variable of drug exposure. In a second study, we propose to investigate that the value of N-Methylspiperone PET Scan as a categorizing variable. Initially we will identify two sub-groups of schizophrenic patients, the Type-I and the Type-II schizophrenics of Crow. Lastly, in a third and separate study, we will compare drug-free patients with tardive dyskinesia with age-matched controls and with age-matched schizophrenic patients without tardive dyskinesia. In all instances, we will be looking primarily for abnormalities in dopamine-2 receptor binding. Additionally, because of the binding characteristics of N-Methylspiperone, we will also be able to investigate for abnormalities in serotonin receptor binding. It is anticipated that the collective data from these studies will be of considerable importance in identifying and characterizing abnormalities in dopamine receptor function that have been postulated for both schizophrenia and tardive dyskinesia.
