Neurochemical brain imaging studies conducted over the past two decades have largely focused on the evaluation of the dopamine system, in particular the striatal D2/D3 dopamine receptor. These studies have evaluated differences in striatal D2/D3 receptor availability between unmedicated patients and demographically matched controls and assessed the time course and magnitude of occupancy of striatal D2/D3 receptors by first and second generation antipsychotic medications. The findings of the occupancy studies have yielded valuable and consistent information with respect to identifying relationships between plasma drug concentrations and receptor occupancy and a therapeutic window for symptom improvement and side effects. However, the data are less consistent with respect to whether striatal D2/D3 receptor availability in the unmedicated state is normal or altered in patients compared to controls, in part perhaps because prior studies were conducted largely in patients who had been previously treated with antipsychotic medications. In addition, the variability between studies and the failure to detect a difference between patients and controls may be related to a lack of consideration of such variables as symptoms at the time of scanning, clinical treatment outcome and D2/D3 receptor polymorphisms.
The specific aims of the project are to evaluate striatal dopamine (D2/D3) receptor availability in first episode schizophrenia patients prior to treatment and to evaluate the association between baseline striatal dopamine (D2/D3) receptor availability and the variance observed between patients in the CIDAR treatment trial, such as symptom response and side effects. Relationship to polymorphisms in dopamine-related genes will also be examined. 65 patients and 40 normal comparison subjects will undergo a Positron Emission Tomography (PET) scan using the well established dopamine (D2/D3) receptor radiotracer [11C]-raclopride. The patients will be antipsychotic naive and will be scanned prior to starting treatment. Having accomplished the specific aims of this project, unique data will be obtained regarding striatal D2/D3 receptor availability in patients with schizophrenia prior to initiating antipsychotic treatment and the relationship to clinical and genetic variables.
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