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) receptors using quantitative [3H]8-OH-DPAT autoradiography on sections of frozen postmortem cerebellum. Production of an ontogenetic map showed that human neonatal cerebellum acquired dense 5-HT1A receptors, most of which were eliminated by early childhood. Autoradiographic measurements on cerebellar vermis from 16 control adult subjects confirmed sparse 5-HT1A receptor binding. The data show a persistence of some vermal 5-HT1A receptors in brains from 19 adults with chronic schizophrenia in whom there may have been a slowed or arrested postnatal regression of vermal 5-HT1A receptors. Alternatively, some 5-HT1A receptors may have been re-expressed prior to, or subsequent to, the onset of the disease symptoms. The findings are not obviously explained by drug treatment 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 schizophrenia, undergoes misdirected reshaping during brain development. The findings support neurodevelopmental hypotheses of the disease.
Slater
P
P
School of Biological Sciences and Department of Psychiatry, Manchester University, United Kingdom.
Doyle
C A
CA
Deakin
J F
JF
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000368:Aged; D001345:Autoradiography; D002531:Cerebellum / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011689:Purkinje Cells / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D011985:Receptors, Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin