COMT Genotype, Schizophrenia, and Dopamine Transmission

dc.contributor.advisorGhose, Subrotoen
dc.creatorBirchfield, Thomas Richarden
dc.date.accessioned2011-02-01T19:33:08Z
dc.date.available2011-02-01T19:33:08Z
dc.date.issued2011-02-01
dc.description.abstractCatechol-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.en
dc.identifier.oclc708581408
dc.identifier.urihttps://hdl.handle.net/2152.5/839
dc.language.isoenen
dc.subjectSchizophreniaen
dc.subjectDopamineen
dc.subjectCatechol O-Methyltransferaseen
dc.titleCOMT Genotype, Schizophrenia, and Dopamine Transmissionen
dc.typeThesisen
dc.type.materialTexten
thesis.date.available2011-01-26
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineRehabilitation Counseling Psychologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelMastersen
thesis.degree.nameMaster of Scienceen

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