Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: an in situ hybridization study.
BACKGROUND
The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia.


METHODS
To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and beta-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and beta-actin mRNA expression levels were measured.


RESULTS
There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of beta-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group.


CONCLUSIONS
There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.
Holt
Daphne J
DJ
Department of Psychiatry, Massachusetts General Hospital East, Room 2625, 149 13th Street, Charlestown, MA 02129, USA. dholt@partners.org
Bachus
Susan E
SE
Hyde
Thomas M
TM
Wittie
Michael
M
Herman
Mary M
MM
Vangel
Mark
M
Saper
Clifford B
CB
Kleinman
Joel E
JE
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*
D002795:Choline O-Acetyltransferase