This study is based on three hypotheses: 1) 5-HT2A serotonin density is decreased in the cortex of schizophrenia patients, 2) 5HT reuptake sites are decreased in SCZ, and 3) the ratio of the 5HT2A/5HT reuptake sites may be abnormal. [11C]MDL100,907, a radiolabeled form of atypical antipsychotic, and [11C]McN5652 that binds with the affinity and selectivity to the 5HT2A receptor and 5HT transporter, respectively, will provide superior information about density of 5-HT2 receptors in the living human brain relative to other ligands that have less receptor specificity. MDL100,907 is a new and highly selective 5HT2A ligand under development in clinical trials of schizophrenia. McN5652(+)is potent reuptake inhibitor and its McN5652 can be used for non-specific binding measure. Studies will be carried out on patients meeting DSMIV criteria for chronic schizophrenia. They will either be drug free or receiving one of two typical antipsychotics, Haldol or Prolixin. These two drugs have low but different affinity to 5HT2A receptor. Studies are performed on an age and gender matched control group. All subjects are on a tryptophan free diet for 24 hours prior to the study. All drug free patients will be studied under Hypothesis 1, 2 and 3. All patients who are currently on medications are studied under hypothesis 2 and 3. All controls are studied under hypothesis 1, 2 and 3. We will evaluate the reliability of the measurements of 5HT2 receptor and transporter in schizophrenics receiving typical antipsychotics. This was done by studying 2-5 normal subjects before and after taking one dose of the same antipsychotic, 7.5 mg of Haldol or 4mg of Prolixin.
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