Platelet serotonin transporter in schizophrenic patients with and without neuroleptic treatment

Abstract

Among various hypotheses put forth to account for the etiology of schizophrenia, the abnormal function of serotonergic system has recently gained marked interest. Our previous study showed that drug-free schizophrenic patients had a significant increase in maximum numbers ( B max) of platelet 5-HT 2A receptors that declined to normal level after treatment with different neuroleptic drugs. To elucidate the role of the serotonin system in schizophrenia, the serotonin transporters on human platelets were examined in this study. Platelet serotonin transporters obtained from normal control subjects and schizophrenic patients were identified by using [ 3H]imipramine as the radioligand and fluoxetine to define the non-specific binding. The data showed that the mean B max of serotonin transporter sites for schizophrenic patients without neuroleptic therapy was significantly higher than in normal controls. The B max values for schizophrenic patients on phenothiazine, butyrophenone, thioxanthene and serotonin-dopamine antagonist (SDA) therapies were significantly lower than the B max values obtained from schizophrenic patients without neuroleptic therapy, and were comparable to those found in normal control subjects. The dissociation equilibrium constant ( K d) values in all subject groups remained unchanged. The effect of various medication periods on platelet serotonin transporters was also studied. We found that, B max values of 1–4 weeks, 1–4 months, 4–12 months and >1 year of neuroleptic therapies were significantly decreased when compared with the unmedicated group. Significant reduction of brief psychiatric rating scale (BPRS) occurred in all types of neuroleptics and every period of drug treatments compared with the unmedicated group. The present results indicate that alteration of platelet serotonin transporters is associated with schizophrenia. Treatment with various types of neuroleptics suppresses the hypersensitivity of platelet serotonin transporters. The mechanisms of how neuroleptics achieve their therapeutic effects, whether they act via or modulate serotonin system in certain brain area, still need to be further evaluated.