vulnerabilities to developing anxiety and mood disorders. Studies have indicated that anxiety and depression share a common genetic diathesis that renders certain individuals vulnerable to develop both types of disorder (Kendler et al 1992). It has been proposed that individual differences in neuroticism may result in vulnerability to subjective distress and negative affect and ultimately development of anxiety and depression (Mineka et al 1998). In an effort to examine underlying genetic vulnerabilities for anxiety and depression, previous studies have observed associations between the serotonin transporter promoter polymorphism and neuroticism (see Schinka et al 2004 for a review). Other studies have examined monoamine oxidase type A (Eley et al 2003), GABA-A (Sen et al 2004), and COMT (Henderson et al 2000; Eley et al 2003; Stein et al 2005). Variations in the COMT polymorphism have been associated with several normally distributed personality traits including harm avoidance (Enoch et al 2003), aggression (Rujescu et al 2003), and neuroticism in some (Eley et al 2003; Stein et al 2005) but not all (Henderson et al 2000) studies. Extraversion has been less studied in association with anxiety; however, Stein and colleagues (2005) observed that COMT polymorphism was associated with lower extraversion among female college students. These authors point out that extraversion is heritable (Jang et al 1996) and has been associated with several anxiety disorders (eg, agoraphobia and social phobia; Bienvenu et al 2001; Bienvenu and Stein 2003). Findings from the current study provide limited support to the associations between the low-enzyme-activity variation of the COMT polymorphism, lower extraversion, and higher neuroticism. The variance in the expression of the personality dimensions that was accounted for by COMT polymorphism is small, consistent with previous literature finding that specific polymorphisms examined alone account for limited variation in the phenotype (eg, Berrettini 1997, 2000). It is important to note that the sample that was examined in the current study included a highly selected healthy subset of the overall population, as individuals with a history of psychiatric disorders and chronic medical illnesses were excluded. This likely reduced the variability in personality traits by excluding individuals with clinically significant anxiety and depression. However, examining the relation- ships within a sample of healthy individuals extends findings in clinical populations in an important way. Differences in the expression of “normal” personality traits may reflect a subtle association between the low-activity genotype and individual vulnerability to subjective distress among adults Neuropsychiatric Disease and Treatment 2006:2(2) COMT polymorphism and personality free of anxiety or mood disorders. Furthermore, there is evidence that neuroticism and to a lesser extent extraversion, are risk factors for mood and anxiety disorders and that in the presence of exposure to stress the personality disorders interact to yield psychopathology. Several studies have observed sex-specific effects of the COMT polymorphism on anxiety; specifically, the associations between the low activity COMT genotype and symptoms of anxiety have been found to be pronounced for females (Eley et al 2003; Olsson et al 2005; Stein et al 2005). In contrast with these previous findings, in the present study there was no evidence of differential sex effects. It is possible that the current study was limited by a relatively small sample size, reducing power to detect subtle effects. Previous studies have examined the association between the COMT polymorphism and anxiety related personality traits by examining females and males separately. In the current study, we investigated potential sex specific effects by statistically testing the interaction between COMT and sex, thus using a more conservative test. Future studies in larger samples of healthy adults will help to clarify potential sex effects. An important contribution of the present study was the examination of the potential interaction between COMT genotype, early life stress, and personality traits associated with anxiety and negative affect. Multiple authors have pointed out that inconsistencies in the neuropsychiatric genetics literature are likely due, in part, to the fact that the expression of behavioral syndromes result from complex gene–environment interactions (eg, Berrettini 1997, 2000). Systematically examining interactions between genetic vulnerabilities and environmental exposure provides an important approach to clarify the multiple factors that influence the expression of anxiety. Exposure to early life stress has been associated with a range of adult psycho- pathology (eg, Harrison et al 1997; Friedman et al 2002). Alterations in the HPA axis and mesolimbic dopamine pathways have been implicated as a potential mechanism by which stress influences the expression of anxiety (Sapolsky 1996; Heim et al 2000). Given that the COMT polymorphism alters dopamine metabolism, the poly- morphism may confer an underlying sensitivity to effects of early life stress via this neurotransmitter system. However, the effects of COMT on dopamine metabolism and subsequently anxiety and depression require further study at the neurochemical level. Our data suggest that exposure to early life stress in itself was associated with higher scores on the personality 223