Elevated dopamine receptor-coupled G(s) protein measures in mononuclear leukocytes of patients with schizophrenia

Heterotrimeric G proteins play a pivotal role in post-receptor information transduction and were previously implicated in the pathophysiology and trea tment of mood disorders. Changes previously detected in G protein levels in post-mortem brain of patients with schizophrenia could reflect effects of antipsychotic medication. The present study aims at quantitatively and func tionally evaluating receptor-coupled G proteins in mononuclear leukocytes o btained from 23 untreated patients with schizophrenia and 30 healthy subjec ts in an attempt to unravel a pattern of G protein measures in schizophreni a distinctive from patterns previously obtained in mood disorders. Dopamine -enhanced guanine nucleotide binding capacity to G(s) protein through D-1/D -5 receptor in mononuclear leukocytes of untreated patients with schizophre nia was significantly increased in comparison with healthy subjects, and po sitively correlated with both the total PANSS score and the positive subsca le. beta -Adrenergic and muscarinic receptor-coupled G protein functions. a s well as G(s)alpha, G(i)alpha and G beta immunoreactivities, were similar to healthy subjects. These findings, distinctive for schizophrenia, unrelat ed to drug treatment, and differential from previous findings in mania and depression, may potentially help to differentially diagnose, after the firs t psychotic episode. between the major psychoses: schizophrenia and manic-d epressive illness. (C) 2001 Elsevier Science B.V. All rights reserved.