title: Manic symptom severity correlates with COMT activity in the striatum: A post-mortem study.
abstract: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity. Nevertheless, the specific relevance of COMT enzymatic activity in the pathophysiology of BD and schizophrenia dimensions remains elusive.
  
  
  
  We measured COMT catalytic activity in post-mortem prefrontal cortices, striata and cerebella of schizophrenia and BD patients, as well as non-affected controls. These values were then correlated with rs4680 genotypes and psychopathology scores in the last week of life.
  
  
  
  No direct correlation between COMT activity and rs4680 genotypes was found; however, the severity of manic symptoms was highly correlated with COMT activity in the striatum, irrespective of the diagnostic group.
  
  
  
  These results suggest that COMT striatal activity, but not rs4680 genotype, may serve as a biomarker for manic symptoms. Future studies are warranted to confirm these findings and assess the neurobiological links between COMT striatal activity and manic symptoms.
authors.affiliation: a Department of Pharmacology and Toxicology, College of Pharmacy , University of Utah , Salt Lake City , UT , USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.affiliation: b Department of Psychiatry and Behavioral Science, School of Medicine , University of Texas Health Science Center , Houston , TX , USA.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Walss-Bass
authors.affiliation: c Southwest Brain Bank, Department of Psychiatry , Texas Tech University Health Science Center at El Paso , El Paso , TX , USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: d Department of Pharmacology and Toxicology, School of Pharmacy , University of Kansas , Lawrence , KS , USA.
authors.forename: Jackob
authors.initials: J
authors.lastname: Moskovitz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D012720:Severity of Illness Index; D014481:United States; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: Catechol-O-methyltransferase; bipolar disorder; manic symptoms; schizophrenia; single nucleotide polymorphism