Hoth et al interaction between COMT genotype, exposure to early life stress, and personality. COMT genotype and ELS severity (high vs low) were entered as fixed factors, with NEO-FFI personality dimensions entered as the dependent variables. An alpha level of 0.05 was retained for all analyses, as specific a priori hypotheses were tested, and the relative risk of Type I error was deemed to be more acceptable than Type II error given the fact that relatively subtle effects were anticipated. Results There were no significant differences on key demographic variables (ie, age, education, sex, number of early life stressful events) between the COMT genotype groups. Allele frequencies did not differ across subsamples collected on each of the continents; thus, all individuals were grouped for the primary analysis. Mean scores on the NEO-FFI are presented in Tables 2 and 3 by COMT genotype and severity of early life stress. Those individuals who were homozygous for the low-activity COMT enzyme allele (Met/Met) had lower scores on the extraversion personality dimension than those participants with the high-enzyme genotype (Val/Val) (F(1,253) = 5.10, p < 0.05); there was a nonsignificant trend for individuals with the low-activity genotype to have higher neuroticism (F(1,252) = 0.10, p = 0.08). The COMT polymorphism accounted for 2.0% of the variance in extraversion and 1.2% of the variance in neuroticism scores. There were no significant statistically significant interactions between COMT genotype and sex for any of the personality dimensions. Approximately 69% of the sample reported exposure to early life stress, with the most common events including hospitalization, severe personal illness, natural disaster, and major family conflict. Of the sample, 54.5% were classified as “low ELS” and 45.5% classified as “high ELS.” Regarding the association between environmental exposure Table 2 Mean scores on the NEO-FFI by COMT genotype COMT genotype Val/Val Met/Met (n = 96) (n = 182) 16.66 (6.65) 31.28 (4.87) 30.62(6.10) 32.23 (5.69) 32.73 (6.10) 18.22 (6.74) 29.72 (5.44) 30.72 (6.24) 31.61 (5.04) 32.18 (7.00) F 3.10 5.10 0.02 0.78 0.40 p value (ANOVA) 0.08 0.03 0.90 0.38 0.53 Measure NEO-FFIa Neuroticism Extraversion Openness Agreeableness Conscientiousness a NEO-Five Factor Inventory 222 Table 3 Mean scores on the NEO-FFI by severity of early life stress NEO-FFIb Neuroticism Extraversion Openness Agreeableness Conscientiousness a Early life stress. b NEO-Five Factor Inventory ELSa severity Low ELS High ELS (n = 261) (n = 211) F p value (ANOVA) 16.69 (6.38) 30.35 (5.66) 29.97 (5.98) 31.96 (5.14) 32.56 (6.89) 19.21 (7.03) 15.66 29.79 (5.65) 0.711 31.47 (6.21) 6.71 31.53 (5.50) 0.74 31.88 (6.38) 1.16 0.001 0.40 0.010 0.39 0.28 to early life stress and mental health, individuals who were exposed to high early life stress endorsed higher neuroticism (F(1,442) = 15.66, p < 0.001) and openness to experience (F(1,445) = 6.71, p < 0.05) on the NEO-FFI than those participants who were not exposed to early life stressful events. The level of exposure to early life stress accounted for 3.4% of the variance in neuroticism scores and 2.0% of the variance in openness to experience. Finally, the interaction between COMT genotype and severity of early life stress was examined. The interaction terms were not statistically significant for any of the NEO-FFI personality dimensions. Discussion The current study extends previous research associating the COMT polymorphism and mental health by assessing personality traits associated with negative affect in a sample of healthy adults, and examining the potential moderating effects of sex and early life stress on these relationships. The results provide weak support for an association between the COMT polymorphism and individual differences in extraversion and neuroticism among a sample of 486 medically and psychiatrically screened healthy adults. Specifically, findings revealed that participants who were homozygous for the COMT low-enzyme-activity allele (Met/ Met) endorsed significantly lower extraversion and a tendency toward higher neuroticism on the NEO-FFI than those with the high-enzyme-activity genotype (Val/Val), though the magnitude of the effect was small. In contrast with previous studies, no sex-specific effects were observed. Finally, exposure to early life stress did not moderate the influence of the COMT low-enzyme-activity genotype on personality. Examining the role of candidate genes on the expression of normally distributed anxiety related traits in healthy individuals provides a strategy to identify underlying genetic Neuropsychiatric Disease and Treatment 2006:2(2)