COMT Genotype, Schizophrenia, and Dopamine Transmission
type: CreativeWork
description: Catechol-o-methyltransferase (COMT) catabolism is the primary mechanism for dopamine signal deactivation in the dorsolateral prefrontal cortex, an area of the brain associated with working memory. Working memory deficits are found in persons with schizophrenia and their unaffected siblings. A single nucleotide polymorphism of the COMT gene results in a MET-->VAL shift at codon 158, increased enzyme thermostability, and increased enzymatic activity. The hypothesized result of this shift is decreased dopamine transmission in the brain area associated with working memory due to increased dopamine catabolism. The current study analyzed the effect of COMT genotype and schizophrenia on the mRNA expression of genes known to be influenced by dopamine signal transmission with qPCR of RNA extracted from high-quality, fresh-frozen postmortem dorsolateral prefrontal cortex tissue. While no significant difference was observed between genotypes, a significant effect of diagnosis was found for the D1 dopamine receptor, COMT, and tyrosine hydroxylase, the rate-limiting step of dopamine synthesis. The current findings support a model decreased dopamine synthesis and increased catabolism leading to deficient dopamine signal transmission in persons with schizophrenia.
abstract: Catechol-o-methyltransferase (COMT) catabolism is the primary mechanism for dopamine signal deactivation in the dorsolateral prefrontal cortex, an area of the brain associated with working memory. Working memory deficits are found in persons with schizophrenia and their unaffected siblings. A single nucleotide polymorphism of the COMT gene results in a MET-->VAL shift at codon 158, increased enzyme thermostability, and increased enzymatic activity. The hypothesized result of this shift is decreased dopamine transmission in the brain area associated with working memory due to increased dopamine catabolism. The current study analyzed the effect of COMT genotype and schizophrenia on the mRNA expression of genes known to be influenced by dopamine signal transmission with qPCR of RNA extracted from high-quality, fresh-frozen postmortem dorsolateral prefrontal cortex tissue. While no significant difference was observed between genotypes, a significant effect of diagnosis was found for the D1 dopamine receptor, COMT, and tyrosine hydroxylase, the rate-limiting step of dopamine synthesis. The current findings support a model decreased dopamine synthesis and increased catabolism leading to deficient dopamine signal transmission in persons with schizophrenia.
author: Birchfield, Thomas Richard
language: en
keywords: Schizophrenia, Dopamine, Catechol O-Methyltransferase
date published: 2011-02-01T19:33:08Z
date modified: 2026-07-24T05:52:15Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/839