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Biol Psychiatry. 2005 Sep 1;58(5):408-16.

Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: an in situ hybridization study.

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Department of Psychiatry, Massachusetts General Hospital East, Room 2625, 149 13th Street, Charlestown, MA 02129, USA.



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.


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.


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.


There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.

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