PET applications in schizophrenia : Functional and pharmacological dopamine studies

Sammanfattning: Schizophrenia is a group of disorders with a worldwide lifetime prevalence of 0.85%. Thefunctional outcome of the disorder seem stable from the first systematic outcome studies to thepresent day, and vary only with changes in diagnostic criteria.Positron emission tomography (PET) has enabled us to quantify receptor populations and inschizophrenia postsynaptic dopamine receptors have been thoroughly studied by use of 11C-raclopride (RAC). The PET tracer of the dopamine precursor L(β-11C)-DOPA, offers anopportunity of studying presynaptic function of the dopaminergic system.Presynaptic dopamine turnover was studied in twelve patients before antipsychotic treatment and compared to healthy volunteers. Increased dopamine synthesis in the striatum could be demonstrated in the patient group thus confirming a dopaminergic dysregulation in striatum. We could also demonstrate an increase in the dopamine synthesis in medial prefrontal cortex, suggesting alterations in limited areas also in cortex.Antipsychotic drug treatment is often the basis for the treatment of schizophrenia. We have studied quetiapine, an antipsychotic compound. In our PET studies we have found a consistent 45-50% dopamine D2 receptor blockade at time of maximum plasma concentration. The receptorblockade rapidly declined and was not detectable after 26 hours. Clinically no motor side effects was noted at any dose level, and we concluded that quetiapine fulfill stringent criteria for an atypical antipsychotic. Some quetiapine treated patients were PET scanned with RAC and the serotonin and dopamine receptor tracer (methylspiperone, NMSP) using the same dose level ofquetiapine as in the previous study. An dopamine D2 blockade could be determined by use of with11C-raclopride, but not when 11C-NMSP was used as the tracer. This difference may explainvariable data in the literature on the dopamine blocking properties of clozapine, the modelatypical antipsychotic.A novel antipsychotic, risperidone, with a more favorable effect/side effect profile compared with classical antipsychotics, was studied for the first time with repeated injections of a risperidone depot formulation in schizophrenic patients. We found an increase in plasma levels with increasing dose risperidone depot. The same trend was found with regard to D2 receptor occupancy. No side effects were noted. The risperidone depot formulation seems to be well suited for maintenance treatment of schizophrenia.

  Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.