Decreased serotonergic responsivity in platelets of drug-free patients with schizophrenia.
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 5HT2 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 5HT2 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.
Yao
J K
JK
Pathology & Laboratory Medicine Service, Department of Veterans Affairs Medical Center, Pittsburgh, PA 15206, USA.
van Kammen
D P
DP
Moss
H B
HB
Sokulski
D E
DE
D000244:Adenosine Diphosphate / Q000502:physiology; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010976:Platelet Count; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D012701:Serotonin / Q000097:blood*
D014150:Antipsychotic Agents; D012701:Serotonin; D000244:Adenosine Diphosphate; D006220:Haloperidol