Decreased serotonergic responsivity in platelets of drug-free patients with schizophrenia

Abstract

We have recently developed a simplified and time-saving method to measure the magnitude of serotonin (5-hydroxytryptamine, 5HT)-amplified platelet aggregation and dense granule secretion (DGS) responses. To study the effects of neuroleptics on peripheral serotonergic function, we measured physiologic responsivity of the platelet 5HT 2 receptor complex in schizophrenic patients ( n = 27), both before and after haloperidol withdrawal, and also in normal volunteers ( n = 18). In human platelets, 5HT amplifies the adenosine diphosphate (ADP)-induced platelet aggregation and DGS. Such an amplification was significantly enhanced in platelets from both normal volunteers and haloperidol-stabilized patients. Following haloperidol withdrawal, however, the magnitude of 5HT-amplified DGS response was no longer significant in drug-free patients, demonstrating a decreased serotonergic responsivity in schizophrenia. Moreover, in drug-free patients, the net changes of ADP-induced DGS, with and without the presence of 5HT, were correlated significantly and negatively with both Bunney-Hamburg psychosis ratings and Brief Psychiatric Rating Scale (total) scores, but not with scores on the Scale for the Assessment of Negative Symptoms. In the drug-free group, no significant difference of 5HT amplification was demonstrated between relapsed and nonrelapsed patients. The present finding thus suggests that drug-free schizophrenic patients may have a reduced physiologic responsivity mediated through the platelet 5HT 2 receptor complex, which can be modified by haloperidol treatment. The pharmacologic action of haloperidol may derive in part from serotonergic mechanisms. The magnitude of 5HT-amplified DGS may be useful in the prediction of therapeutic outcome after haloperidol treatment.