Hoth et al 1999; Henderson et al 2000). The COMT polymorphism has also been examined in relation to obsessive-compulsive disorder (Schindler et al 2000; Azzam and Mathews 2003; Erdal et al 2003; Olsson et al 2005), phobic anxiety (Ohara et al 1998a; McGrath et al 2004), and panic disorder (Hamilton et al 2002; Woo et al 2004) with mixed results. Several recent studies examined the association between COMT and personality traits in nonclinical samples. Eley and colleagues (2003) explored the role of monoamine oxidase type A (MAOA) and COMT on the expression of neuroticism using a selected extremes design. The authors reported an excess of the low-activity genotype among females with high neuroticism. The focus on neuroticism in the study by Eley and colleagues (2003) provided a unique contribution to the literature; however, several aspects of the study warrant further s t u d y. F i r s t , t h e a u t h o r s o b t a i n e d p e e r- r e p o r t o f participants’ personality using a translated version of the NEO-FFI, rather than using the original standardized self- report measure. In addition, only data from the top and bottom 10% of scores on the neuroticism measure were analyzed in the study. Selecting only those individuals with the most extreme personality scores may have biased the relationships by focusing only on critical aspects of the normal distribution. Stein and colleagues (2005) extended the findings described above by examining the hypothesis that functional variants in the COMT gene would be associated with both high neuroticism and low extraversion among a sample of 497 college students. Results revealed that two of the three single nucleotide polymorphisms examined were associated with low extraversion and high neuroticism, with the effects confined to women. Overall, the authors concluded that the involvement of COMT is unlikely to be entirely attributable to the Val/Met polymorphism. Future research examining the additional contribution of other factors such as other genetic variation and gene–environment interactions may clarify the relationships. Early life stress represents one important environmental condition that may affect genetic vulnerabilities to adult psychosocial health. In a recent study, Henderson and colleagues (2000) examined COMT and DRD3 poly- morphisms in a large community sample. In this study, there was no relationship between COMT and DRD3 poly- morphisms and personality traits conferring vulnerability to anxiety or depression. Results also revealed no relationship between DRD3 genotype and exposure to childhood and recent environmental stressors; interestingly, 220 the relationships between COMT polymorphism, early life stress, and mental health were not examined. In the present study we examined the association between COMT genotype and personality among a cohort of healthy adults. Consistent with previous studies, we hypothesized that individuals with the Met/Met genotype (low enzyme activity) would report higher levels of neuroticism and lower extraversion on the NEO-FFI than individuals with the Val/Val genotype (high activity enzyme). We also examined the relationship between COMT and personality traits by sex. We expected that the association between COMT and neuroticism and extraversion would be stronger for females than for males. In addition, to further clarify the association between COMT genotype and anxiety-related personality traits, we examined the interaction between genotype and environmental exposure to early life stress. Exposure to early life stress was expected to moderate the association between COMT genotype and neuroticism and extraversion. Specifically, we hypothesized that individuals with both the Met/Met genotype and a history of early life stress would endorse greater neuroticism and lower extraversion. Methods Procedures All individuals in the present study were participants in a large multi-site, multi-national study of brain function, including, in part, emotional and genetic data (Brain Resource International Database, BRID www.brainresource.com; Gordon 2003; Gordon et al 2005). As part of the parent study, individuals were excluded if they had a history of any medical (eg, diabetes, hypertension, stroke, degenerative disease, thyroid disease), or psychiatric condition (eg, psychosis, mood disorder). The screening procedure included a comprehensive web-based medical history questionnaire and the SPHERE (Hickie et al 2001). Participants were examined at one of five research sites in Australia, North America, and Europe. Written informed consent was obtained for all individuals after receiving a thorough explanation of the study. The parent study was approved by local IRBs at each of the participating research sites. Participants were financially compensated for participation. Genotyping Genomic DNA was extracted from cheek swabs. Buccal cells were pelleted by centrifugation and digested overnight Neuropsychiatric Disease and Treatment 2006:2(2)