RECENT DEVELOPMENTS IN PET SCAN IMAGING OF NEURORECEPTORS IN SCHIZOPHRENIA

Among the brain imaging techniques developed during the past two decad es, positron emission tomography (PET) has the highest sensitivity all owing the analysis of specific neurotransmitter mechanisms in the livi ng human brain. By using a combination of selective ligands labeled wi th positron emitting isotopes D1 - and D2 dopamine, serotonin 5HT2, an d benzodiazepine receptors were examined in schizophrenic patients (DS M-III-R) and healthy control subjects. With this technique receptor po pulations could be excellently visualized and quantified with regard t o number and binding characteristics in several brain regions. The cha racteristics of the total D1 and D2 dopamine receptor populations in t he caudate and putamen did not differ in young drug-naive schizophreni c patients and age-matched control subjects. Also for 5HT2 and benzodi azepine receptors no major alteration of receptor characteristics was observed in several neocortical and limbic brain regions. However, in schizophrenic patients treated with chemically different types of anti psychotic drugs major reductions of ligand binding was observed indica ting specific induction of neuroreceptor occupancy. Thus, all chemical ly different types of antipsychotic drugs examined induced a substanti al occupancy of D2 dopamine receptors. Clozapine in high doses induced a significantly lower degree of D2 dopamine receptor occupancy than t he conventional drugs. Some but not all antipsychotics also induced a significant D1 dopamine receptor occupancy. In spite of the fact that the selective D1 antagonist SCH 39166 induced a substantial D1 occupan cy, this drug did not exhibit an antipsychotic effect in schizophrenic patients. A very high degree of 5HT2 occupancy in neocortical regions was observed after clinical treatment with antipsychotic drugs as clo zapine, risperidone and thioridazine. Haloperidol did not affect 5HT2 occupancy. There was no major alteration of benzodiazepine receptor oc cupancy during antipsychotic drug treatment. Quantitative relationship s between D2 dopamine receptor occupancy and extrapyramidal side-effec ts as well as antipsychotic effect could also be growing potential of PET scan imaging for diagnostic purposes in neuropsychiatric disorders and also for the elucidation of mechanisms of antipsychotic drug acti on as well as in clinical practice and for the rehabilitation of schiz ophrenic patients.