Gene-brain-behavior relationships: Evidence that aggression is associated with brain MAO A activity in healthy males

Abstract

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Objectives: Differences in brain and behavior have been reported from individuals stratified solely by polymorphism in the promoter region of the monoamine oxidase A genotype (MAO A, low or high). The low MAO A genotype was associated with aggressive behavior. In turn, the relationship between brain MAO A activity and traits as aggression is unexplored, prompting this study. Methods: Brain MAO A activity was measured in cortical and subcortical regions with PET and [11C]clorgyline (an irreversible MAO A-specific radiotracer), in 38 healthy non-smoking males who were genotyped for MAO A uVNTR. Subjects were assessed for verbal and non-verbal intelligence (Reading Achievement and Matrix Reasoning) the Beck Depression Inventory and Multidimensional Personality Questionnaire (MPQ; n=27). Results: High (n=26) and low (n=12) MAO A genotype groups did not differ on any of the measures. However, MAO A activity correlated only to trait aggression in both cortical and subcortical brain regions (range: r=-0.53-0.60, p=0.03-0.0004) correcting for non-verbal intelligence (which was correlated with brain MAO A activity across the genotype groups: r=-0.34, p<0.05) and not to negative emotionality nor with depression (p>0.10). Conclusions: Subjects with higher scores on trait aggression had lower MAO A activity throughout the brain and this association was similar for both MAO A genotype groups. This finding corroborates the relevance of brain MAO A in aggressive behaviors. Lack of association between the genotype and aggression could reflect a gene X environment interaction, which may be necessary for the expression of an aggressive phenotype.

Research Support (if any): DOE-OBER, NIDA (K05 DA 020001) and NARSAD