ELEVATED PLATELET CALCIUM MOBILIZATION AND NITRIC-OXIDE SYNTHASE ACTIVITY MAY REFLECT ABNORMALITIES IN SCHIZOPHRENIC BRAIN

Schizophrenia has a diverse nature of clinical symptoms and a number o f hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, recepto r-activated calcium mobilization and calcium activated nitric oxide sy nthase activity in schizophrenic subjects. Thrombin induces mobilizati on of calcium ions from intracellular stores. The platelet response of drug naive schizophrenics was found to be significantly increased ove r a range of thrombin concentrations (0.01 to 0.60 U/ml) compared to c ontrol subjects. Possible involvement of nitric oxide (NO) in the aeti ology of schizophrenia was investigated. NO has been functionally link ed to both dopaminergic and glutamatergic systems both of which are st rongly implicated in the biochemical pathology of schizophrenia. Nitri c oxide synthase (NOS) activity was determined in platelets of control s, schizophrenic and panic disorder subjects. Enzyme activity was foun d to be significantly higher in platelets of drug naive schizophrenic subjects compared to controls, drug treated schizophrenics and panic d isorder subjects. It is suggested that there is an imbalance of the ca lcium-induced L-arginine- nitric oxide pathway in platelets of schizop hrenic subjects which may be modified by neuroleptic treatment. This i mbalance may be mirrored in the central nervous system in particular a t the NMDA receptor. It is possible that such a disturbance in the L-a rginine-nitric oxide pathway may have pathological implications in the aetiology of schizophrenia. (C) 1995 Academic Press, Inc.