Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health

Objectives 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 Val(158)Met genotypes and catechol-O-methyltransferase activity. Compared with the Val(158)Val genotype, the Val(158-1) Met and Met(158)Met genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively. Two recent reports have observed the association between the Met(158)Met genotype and risk of anxiety in adult populations. We examined the association between the Val(158)Met 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 Met(158)Met genotype (odds ratio 2.0, 95% confidence interval 1.1-3.4, P=0.014). A dose relationship between additional copies of the Met(158) 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(158) allele was among females only. No association was observed for measures of neuroticism, persistent generalized anxiety, or a composite measure of psychiatric distress. Conclusion These data replicate previous findings suggesting association between the Val(158) Met polymorphism and specific expressions of anxiety among females. (c) 2005 Lippincott Williams & Wilkins.