We first checked, in each population, whether there was a difference in ASPD trait scores between high and low activity subjects (). Amongst Caucasians, the mean ASPD trait score for low activity subjects was 2.14 whereas it was 1.9 for high activity subjects, which was not significantly different. Amongst African Americans, the mean ASPD trait score for low activity subjects was 2.2 whereas it was 2.15 for high activity subjects, which was also not significantly different.
Mean number of adult ASPD items scored “1” or “2” by MAOA allele.
We had previously observed both high reports of childhood physical abuse in the HEPS sample and a strong correlation between it and later ASP.22
To determine whether MAOA alleles modified the risk of ASP after childhood physical abuse, we analyzed this relationship separately in subjects who reported abuse and those that did not (). We did not find that MAOA activity modified the number of ASPD traits in subjects who had been physically abused. In fact, ASPD trait scores were non-significantly lower amongst Caucasians with a history of abuse and low activity MAOA activity. However, in Caucasian subjects with no history of childhood physical abuse, mean ASPD trait score was 1.38 in high activity subjects and 1.94 in low activity subjects (p<0.05), an increase of 41%. When Native Americans, Hispanics, Asians and ‘Other’ were excluded from the analysis, the results were very similar with the ASPD trait score amongst “true” Caucasians at 1.37 for high activity allele subjects and at 1.97 (p<0.05) for low activity allele subjects, an increase of 44%. Similar trends were also obtained when Caucasian males and females were analyzed separately, although the results did not reach statistical significance. ASPD trait scores amongst African Americans with no history of abuse were virtually identical in low and high MAOA activity subjects. Also the chances of experiencing childhood physical abuse were not significantly affected by MAOA allele length in either Caucasians or African Americans.
To further evaluate the relative roles of physical abuse and the MAOA allele in ASPD trait scores amongst Caucasians, we performed a multiple linear regression analysis with ASPD trait score as the dependent variable and physical abuse, the MAOA allele and a physical abuse × MAOA allele interaction term as independent variables. The results shown in support the stratification analysis although the effect of the interaction term did not reach statistical significance. The data suggest reporting a history of childhood physical abuse is associated with an approximately one point higher ASPD trait score on average than not reporting physical abuse regardless of MAOA allele type, consistent with the stratification analysis. Among those not reporting a history of childhood physical abuse, the high activity allele is associated with approximately a half-point lower ASPD trait score than that of the low activity allele, also consistent with the stratification analysis. The data also suggest that the effect of physical abuse is stronger for those with the high activity MAOA allele compared with those the low activity allele. As the ASPD trait score is a right-skewed score running from 0–7 and thus not normally distributed, we also performed ordinal logistic regression to assess sensitivity to failure of normality, and findings were qualitatively and quantitatively similar.
Multiple linear regression analysis of effects of physical abuse, MAOA allele and the interaction term physical abuse × MAOA allele on number of adult antisocial personality traits amongst Caucasians.
We also evaluated how MAOA allele activity influences the likelihood of each ASPD trait in Caucasians and African Americans who had not suffered physical abuse (). Amongst Caucasians, the proportion of subjects positive on each trait was higher in those with the low activity allele compared with those with the high activity allele. The difference was statistically significant at the 0.05 level for “Impulsivity to plan ahead” and for “Lack of remorse”, and significant at the 0.1 level for “Reckless disregard for safety of self and others”. Amongst African Americans, there was no pattern or trend regarding likelihood of being positive on a trait amongst individuals with low versus high allele activity genotypes.
Proportion of subjects without a history of physical abuse scoring “1” or “2” on each antisocial personality disorder trait by MAOA allele.
We also used an alternate methodology to confirm our finding that MAOA genotype influences ASPD trait score in Caucasians who have not suffered physical abuse. We checked NEO trait scores by MAOA allele activity in Caucasians who had not suffered childhood physical abuse (using a two-tailed unpaired t test). We found that individuals with low activity alleles had higher neuroticism factor scores than those with high activity alleles (p<0.1). Several neuroticism facet scores, namely vulnerability (p<0.1), angry hostility (p<0.05) and anxiety (p<0.05) were higher in individuals with low activity compared with high activity alleles. Individuals with low activity alleles also had lower scores on the agreeableness factor (p<0.05) and lower agreeableness facet scores on trust (p<0.05), altruism (p<0.05) and compliance (p<0.1). We also evaluated whether an expert generated prototypic ASPD profile generated by Lynam and colleagues varied by MAOA allele. Prototypes formed by experts have been used to verify the facets that capture pure antisocial traits.30,31
Miller et al.32
developed a NEO-PI-R index which captures DSM-IV antisocial personality disorder criteria, comprising the sum of 17 individual facets (see Supplementary Data
). We found that individuals with low activity alleles had higher scores on the scale than those with high activity alleles (p<0.1).
We also checked whether the MAOA polymorphism influenced childhood conduct disorder scores in Caucasians with no history of childhood physical abuse. We did not find MAOA genotype influenced conduct disorder scores when scores of ‘1’ and ‘2’ were assigned a value of one. However, when scores of ‘1’ were assigned a value of zero and scores of ‘2’ were assigned a value of one, creating a scale which reflected severe childhood conduct pathology, those with low activity MAOA alleles had significantly higher scores than those with high activity alleles (p<0.01, Mann-Whitney U test). Amongst childhood conduct disorder traits, those that were significantly more like to score ‘2’ compared with ‘0’ or ‘1’ amongst low activity individuals were “Lied/conned” (p<0.01), “Destroy property” (p<0.1), “Burglary” (p<0.05) and “Truant” (p<0.05). (For these calculations we used a Pearson’s chi-square test to compare rates between MAOA alleles except when a cell contained less than 5 subjects in which case we used a Fisher’s exact test.)