Dopamine- and serotonin-receptors in schizophrenia: results of imaging-studies and implications for pharmacotherapy in schizophrenia

Considerable progress has been achieved over the past 15 years in uncoverin g the biological basis of major psychiatric disorders. Since psychopharmaco logical treatment is thought to act on the underlying biological basis of t he disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. Positron emission tomography (PET) as well as single photon emission computerized tomography (SPECT) are important tools used to determine patterns of brain dysfunction and to uncover the mechanis m of action for antipsychotic compounds. These techniques allow us to deter mine striatal D-2 receptor as well as cortical 5-HT2A receptor occupancy ra tes which are linked, at least partly, to clinical efficacy as well as side effect rates. In general it has been shown that atypical antipsychotics ha ve a lower striatal D-2 receptor occupancy rate than typical antipsychotics , parallelling the more favorable extrapyramidal side effects of atypical a ntipsychotics, and as a group effect they have a high 5-HT2, occupancy comp ared to low rates for typical agents. However, there is no association betw een striatal D-2 receptor occupancy rates and antipsychotic efficacy but 5- HT2A occupancy rates are associated with favorable treatment for depressive symptoms within schizophrenia and improvement of cognitive function. The a vailability of ligands for measurement of extrastriatal D-2 receptors or di fferent 5-HT receptors (e.g. 5-HT1A) will further shed light on the pathoph ysiology of schizophrenia as well as possible psychopharmacological treatme nt perspectives.