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

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.
Authors	Mayada Akil, Bhaskar S Kolachana, Debora A Rothmond, Thomas M Hyde, Daniel R Weinberger, Joel E Kleinman
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 23 Issue 6 Pg. 2008-13 (Mar 15 2003) ISSN: 1529-2401 [Electronic] United States
PMID	12657658 (Publication Type: Journal Article)
Chemical References	Dopamine Plasma Membrane Transport Proteins Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins RNA, Messenger Tyrosine 3-Monooxygenase Catechol O-Methyltransferase Cyclophilins Dopamine
Topics	Adult Alleles Amino Acid Substitution Autoradiography Brain (cytology, metabolism) Catechol O-Methyltransferase (genetics) Corpus Striatum (cytology, metabolism) Cyclophilins (biosynthesis, genetics) Dopamine (metabolism) Dopamine Plasma Membrane Transport Proteins Female Genotype Humans In Situ Hybridization Male Membrane Glycoproteins Membrane Transport Proteins (biosynthesis, genetics) Mesencephalon (cytology, metabolism) Middle Aged Nerve Tissue Proteins Neurons (metabolism) Prefrontal Cortex (metabolism) RNA, Messenger (analysis, biosynthesis) Reference Values Schizophrenia (genetics) Tyrosine 3-Monooxygenase (biosynthesis, genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!