title: Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains.
abstract: Catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamine neurotransmitters within the brain. A functional polymorphism COMT Val158Met has been associated with psychiatric disorders including suicidal behavior. In the present study we examined whether this polymorphism was related to COMT mRNA expression in frontal cortical regions, and whether the expression of COMT differed between depressed suicide victims and psychiatric healthy controls. The Val158Met polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The levels of COMT mRNA expression in the frontopolar cortex (FPC; 29 suicides vs. 27 controls) and orbital frontal cortex (OFC; 19 suicides vs. 15 controls) were significantly increased among depressed individuals that died by suicide relative to those of controls, being up-regulated by approximately 60% and 65% in the FPC and OFC, respectively. Furthermore, among individuals with the Met allele (Met/Met and Met/Val genotypes) who died by suicide COMT mRNA expression was elevated relative to that of the nondepressed Met allele carriers. However, significant differences were not detected between suicides (n=49) and controls (n=72) with respect to the Val158Met genotypic distribution and allelic frequencies. These results are consistent with the perspective that altered COMT mRNA expression in frontal cortical brain regions might contribute to suicide and/or depression, further supporting the role of dysregulation of catecholaminergic pathway genes in the pathophysiology of suicide behaviors.
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada. Electronic address: lishengdu@gmail.com.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Du
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada.
authors.forename: Zul
authors.initials: Z
authors.lastname: Merali
authors.affiliation: Molecular Brain Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
authors.affiliation: Neuromorphological and Neuroendocrine Research Laboratory, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.affiliation: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Faludi
authors.affiliation: Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics*; D003863:Depression / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism*; D013405:Suicide; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002394:Catechol O-Methyltransferase
keywords: COMT polymorphism; Depression; Prefrontal cortex; Suicide; mRNA expression