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

Abstract

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought to act on the underlying biological basis of the 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 mechanism of action for antipsychotic compounds. These techniques allow us to determine striatal D₂ receptor as well as cortical 5-HT_2A receptor occupancy rates which are linked, at least partly, to clinical efficacy as well as side effect rates. In general it has been shown that atypical antipsychotics have a lower striatal D₂ receptor occupancy rate than typical antipsychotics, parallelling the more favorable extrapyramidal side effects of atypical antipsychotics, and as a group effect they have a high 5-HT_2A occupancy compared to low rates for typical agents. However, there is no association between striatal D₂ receptor occupancy rates and antipsychotic efficacy but 5-HT_2A occupancy rates are associated with favorable treatment for depressive symptoms within schizophrenia and improvement of cognitive function. The availability of ligands for measurement of extrastriatal D₂ receptors or different 5-HT receptors (e.g. 5-HT_1A) will further shed light on the pathophysiology of schizophrenia as well as possible psychopharmacological treatment perspectives.