ISOTYPE-SPECIFIC G-PROTEIN ABNORMALITIES IN THE LEFT SUPERIOR TEMPORAL CORTEX AND LIMBIC STRUCTURES OF PATIENTS WITH CHRONIC-SCHIZOPHRENIA

Background: The potential role of signal transducing guanine nucleotid e-binding regulatory protein (G protein) in schizophrenia is largely u nknown. Methods: We immunoquantified isotypes of G protein using speci fic antisera against alpha and beta subunits of G protein in the super ior temporal, prefrontal, and entorhinal cortices as well as the nucle us accumbens and amygdala of postmortem brains from 19 schizophrenic a nd 28 control subjects. Results: In the left hemisphere of schizophren ics, the amount of Gi alpha, Go alpha, and Gq alpha but not that of Gs alpha or G beta decreased in the superior temporal cortex by 27%, 27% , and 16%, respectively, as compared with the values in ipsilateral co ntrols; the amount of any G protein isotype in the prefrontal and ento rhinal cortices was not changed In the nucleus accumbens and amygdala, the paranoid type schizophrenics showed a smaller amount of Gi alpha and Go alpha than the disorganized type schizophrenics. In the right s uperior temporal cortex, the isotype amount did not differ between the schizophrenic and control groups. Conclusions: The decreased Gq alpha immunoreactivity in the schizophrenic left superior temporal cortex m ay reflect the down-regulation of Gq alpha, resulting from chronic sti mulation of Gq alpha-coupled receptors, while the decreased Gi alpha a nd Goer in the nucleus accumbens and amygdala of paranoid type schizop hrenics may be related to the dopaminergic hyperactivity via dopamine D-2 receptors. (C) 1998 Society of Biological Psychiatry.