ObjectiveWomen are more prone to anxiety than men. The catechol-O-methyltransferase functional polymorphism, Val158Met, is likely to be implicated in anxiety vulnerability. We hypothesized that, particularly in women, the low-activity Met158 allele would be associated with higher anxiety scores and a biological trait, low-voltage alpha resting electroencephalogram (EEG), previously associated with alcoholism and anxiety disorders.MethodsDNA was obtained from two independent groups of participants ascertained as community samples: 149 predominantly Caucasian individuals (92 women, 57 men), and 252 Plains American Indians (149 women, 103 men). Dimensional measures of anxiety (Tridimensional Personality Questionnaire harm avoidance subscales HA1 and HA2) were obtained and DSM-III-R lifetime psychiatric diagnoses were determined. EEGs were recorded and EEG phenotypes assigned.ResultIn both populations, women showed significant associations between catechol-O-methyltransferase genotype and elevated harm avoidance scores, and the Met158/Met158 genotype was most strongly associated: predominantly Caucasian participants: HA1,P=0.03, HA2,P=0.03; and Plains American Indians: HA2,P=0.01. This was also the case with low-voltage alpha resting EEG: predominantly Caucasian participants:P=0.01, odds ratio=5.0 (95% confidence interval, 1.3–18.7); Plains American Indians:P=0.03, odds ratio=3.7 (95% confidence interval, 1.1–12.7).ConclusionsThe results of the present study suggest that an inherited difference in catecholamine metabolism is important in the pathogenesis of anxiety in women.