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Intracellular free calcium concentrations ([Ca2+]1) were measured in platelets from healthy volunteers before and after adding thrombin, chlorpromazine, haloperidol and/or lithium, and in platelets from DSM-III-R diagnosed schizophrenic patients receiving neuroleptic medication. Thrombin increased [Ca2+] 1 in a dose- dependent fashion. Chlorpromazine and haloperidol also mobilized Ca2+ in a dose-dependent fashion, and augmented the response to low doses of thrombin without changing the maximal response to thrombin. The effects of all three drugs were not additive, suggesting that they affected the same intraplatelet calcium pool; most likely the dense tubular system. Lithium also increased [Ca2+ ] but without affecting the response to thrombin, chlorpromazine or haloperidol. The effects of the latter three drugs were additive to that of lithium, suggesting that lithium was acting on a different calcium pool. The response to thrombin was significantly lower in platelets from schizophrenic patients than in platelets from healthy volunteers. Further studies are required to explore potential causes for this observation. Such causes include schizophrenia per se and chronic neuroleptic treatment.

Abnormalities in blood cell membrane phospholipid composition and metabolism from schizophrenic patients have been reported by many groups of investigators. Among membrane phospholipids, inositol phospholipids are of special importance as they are involved in transduction system that generates second messengers such as inositol trisphosphate and diacylglycerol. Our studies on platelet inositol phospholipid turnover suggest a significant increase in platelet phosphatidylinositol 4,5-bisphosphate levels, an increased production of inositol trisphosphate in neuroleptic-treated and neuroleptic-free schizophrenic patients platelets and a reduced calcium release by thrombin in neuroleptic-treated schizophrenic patients platelets. The enhanced production of inositol trisphosphate may be due to an increase in its precursor phosphatidylinositol 4,5-bisphosphate with an associated desensitisation of the intracellular inositol trisphosphate receptor by neuroleptics, which may explain the diminished calcium response to thrombin in schizophrenic patients platelets.