Catechol-O-methyltransferase genotype and dopamine regulation in the human brain

Mayada Akil, Bhaskar S. Kolachana, Debora A. Rothmond, Thomas M. Hyde, Daniel R. Weinberger, Joel E. Kleinman

Research output: Contribution to journalArticle

Abstract

A functional polymorphism in the gene for catechol-O-methyltransferase (COMT) has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans, probably by affecting prefrontal dopamine signaling. The COMT valine allele, associated with relatively poor prefrontal function, is also a gene that may increase risk for schizophrenia. Although poor performance on executive cognitive tasks and abnormal prefrontal function are characteristics of schizophrenia, so is psychosis, which has been related to excessive presynaptic dopamine activity in the striatum. Studies in animals have shown that diminished prefrontal dopamine neurotransmission leads to upregulation of striatal dopamine activity. We measured tyrosine hydroxylase (TH) mRNA in mesencephalic dopamine neurons in human brain and found that the COMT valine allele is also associated with increased TH gene expression, especially in neuronal populations that project to the striatum. This indicates that COMT genotype is a heritable aspect of dopamine regulation and it further explicates the mechanism by which the COMT valine allele increases susceptibility for psychosis.

Original languageEnglish (US)
Pages (from-to)2008-2013
Number of pages6
JournalJournal of Neuroscience
Volume23
Issue number6
DOIs
StatePublished - Mar 15 2003

Keywords

  • Catechol-O-methyltransferase
  • Dopamine
  • Genotype
  • Human
  • Midbrain
  • Psychosis
  • Schizophrenia
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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