ABNORMAL PERSISTENCE OF CEREBELLAR SEROTONIN-1A RECEPTORS IN SCHIZOPHRENIA SUGGESTS FAILURE TO REGRESS IN NEONATES

This study investigated the neurodevelopmental basis of schizophrenia by examining an early transient population of serotonin-1A (5-HT1A) re ceptors using quantitative [H-3]8-OH-DPAT autoradiography on sections of frozen postmortem cerebellum. Production of an ontogenetic map show ed that human neonatal cerebellum acquired dense 5-HT1A receptors, mos t of which were eliminated by early childhood. Autoradiographic measur ements on cerebellar vermis from 16 control adult subjects confirmed s parse 5-HT1A receptor binding. The data show a persistence of some ver mal 5-HT1A receptors in brains from 19 adults with chronic schizophren ia in whom there may have been a slowed or arrested postnatal regressi on of vermal 5-HT1A receptors. Alternatively, some 5-HT1A receptors ma y have been re-expressed prior to, or subsequent to, the onset of the disease symptoms. The findings are not obviously explained by drug tre atment and there are no data to explain how neuroleptics might promote expression of cerebellar 5-HT1A receptors. We propose that the study has identified a neurotransmitter receptor population which, in schizo phrenia, undergoes misdirected reshaping during brain development. The findings support neurodevelopmental hypotheses of the disease.