title: Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health.
abstract: OBJECTIVE
  Catechol-O-methyltransferase plays a central role in the metabolism of biogenic amines such as norepinephrine, dopamine and serotonin. Functional studies have demonstrated a dose relationship between ValMet genotypes and catechol-O-methyltransferase activity. Compared with the ValVal genotype, the ValMet and MetMet genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively. Two recent reports have observed the association between the MetMet genotype and risk of anxiety in adult populations. We examined the association between the ValMet genotypes and propensity to anxiety across adolescence.
  
  
  METHODS
  Participants were drawn from an eight-wave study of the mental and behavioural health of over 2000 young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 to present). DNA was received from 962 participants using a cheek swab collection method.
  
  
  RESULTS
  The odds of reporting persistent episodic anxiety (phobic avoidance, panic attacks) were doubled among carriers of the MetMet genotype (odds ratio 2.0, 95% confidence interval 1.1-3.4, P=0.014). A dose relationship between additional copies of the Met allele and persistent episodic anxiety was also observed (1.5, 1.1-1.94, P=0.007). Stratification by sex showed that the risk effect of the Met allele was among females only. No association was observed for measures of neuroticism, persistent generalized anxiety, or a composite measure of psychiatric distress.
  
  
  CONCLUSIONS
  These data replicate previous findings suggesting association between the ValMet polymorphism and specific expressions of anxiety among females.
authors.affiliation: Centre for Adolescent Health, Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Victoria, Australia. craig.olsson@rch.org.au
authors.forename: Craig A
authors.initials: CA
authors.lastname: Olsson
authors.forename: Richard J L
authors.initials: RJ
authors.lastname: Anney
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Lotfi-Miri
authors.forename: Graham B
authors.initials: GB
authors.lastname: Byrnes
authors.forename: Robert
authors.initials: R
authors.lastname: Williamson
authors.forename: George C
authors.initials: GC
authors.lastname: Patton
mesh_terms: D000293:Adolescent; D016497:Adolescent Health Services; D000328:Adult; D019943:Amino Acid Substitution; D001007:Anxiety / Q000235:genetics*; D001315:Australia; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014633:Valine
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine