Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia: An in situ hybridization study

Daphne J. Holt, Susan E. Bachus, Thomas M. Hyde, Michael Wittie, Mary M. Herman, Mark Vangel, Clifford B. Saper, Joel E. Kleinman

Research output: Contribution to journalArticlepeer-review


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 β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-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 β-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.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalBiological psychiatry
Issue number5
StatePublished - Sep 1 2005
Externally publishedYes


  • Basal ganglia
  • Cholinergic
  • In situ hybridization
  • Postmortem
  • Schizophrenia
  • Striatum

ASJC Scopus subject areas

  • Biological Psychiatry


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