Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia

Mitsuyuki Matsumoto, Cynthia Shannon Weickert, Senda Beltaifa, Bhaskar Kolachana, Jingshan Chen, Thomas Hyde, Mary M. Herman, Daniel Weinberger, Joel Kleinman

Research output: Contribution to journalArticle

Abstract

Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism of COMT, Val108/158 Met, affects prefrontal function, and the high-activity Val allele has been reported to be a genetic risk factor for schizophrenia. We used in situ hybridization histochemistry to measure mRNA levels of COMT in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia (N = 14) and of normal controls (N = 15). While the groups did not differ in terms of mean level of COMT mRNA, there was a significantly different laminar pattern of COMT mRNA expression in pyramidal neurons (F = 2.68, df = 4,108, P < 0.04); patients with schizophrenia had relatively lower levels in the superficial (II/III) layers and higher levels in the intermediate/deep (IV/V) layers (P<0.01), while in controls, the expression was homogeneous across layers. Neither the mean level nor the laminar distribution of COMT mRNA was related to the Val108/158 Met genotype, suggesting that the feedback regulation of mRNA level is not a compensation for the functional effect of the COMT polymorphism. The disease-related laminar difference of COMT expression may be involved in dysregulation of dopamine signaling circuits in the DLPFC of patients with schizophrenia.

Original languageEnglish (US)
Pages (from-to)1521-1530
Number of pages10
JournalNeuropsychopharmacology
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2003
Externally publishedYes

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Keywords

  • Cortical layer
  • DLPFC
  • Dopamine
  • Functional Val/Met polymorphism
  • Human brain
  • In situ hybridization histochemistry
  • Pyramidal neuron

ASJC Scopus subject areas

  • Pharmacology

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