Association between the COMT Val158Met polymorphism and... : Psychiatric Genetics (original) (raw)

ORIGINAL ARTICLES

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

Olsson, Craig A.a b; Anney, Richard J.L.b; Lotfi-Miri, Mehrnoushb; Byrnes, Graham B.c; Williamson, Robertb; Patton, George C.a

aCentre for Adolescent Health, Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne

bBehavioural Genetics Laboratory, Murdoch Childrens Research Institute, University of Melbourne, Department of Paediatrics, Royal Children's Hospital, University of Melbourne

cSchool of Population Health, University of Melbourne, Victoria, Australia

Correspondence and requests for reprints to Dr. Craig Olsson, Centre for Adolescent Health, 2 Gatehouse Street, Parkville 3052 Victoria, Australia

Tel: +61 03 9345 6250; fax: +61 03 9345 6502;

e-mail: [email protected]

Abstract

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 Val158Met genotypes and catechol-O-methyltransferase activity. Compared with the Val158Val genotype, the Val158Met and Met158Met genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively. Two recent reports have observed the association between the Met158Met genotype and risk of anxiety in adult populations. We examined the association between the Val158Met 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 Met158Met genotype (odds ratio 2.0, 95% confidence interval 1.1–3.4, _P_=0.014). A dose relationship between additional copies of the Met158 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 Met158 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 Val158Met polymorphism and specific expressions of anxiety among females.