Brain monoamine oxidase A activity predicts trait aggression

Abstract

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression.

Figures

Figure 1.

Trait aggression and brain MAO A activity in cortical regions (left) and in subcortical regions (right). The r and p values at the top of each scatter plot represent the correlation value and significance for the whole population (df = 25). The units of MAO A activity, λk3, are an index of the amount of catalytically active MAO A. Data from the two hemispheres was combined by averaging the right and the left sides of each region. White circles denote low MAO A genotype (n = 10), and black circles denote high MAO A genotype (n = 17).

Figure 2.

Brain MAO A activity in aggressive and in nonaggressive participants. On the left vertical panel marked as “A” is averaged images of participants who endorsed 10 or more aggression questions (n = 4). On the right is an averaged image of participants who endorsed two or less aggression questions (n = 5; marked as “N”) based on 1 SD above or below the aggression mean for this sample. The images are presented in continuous axial slices throughout most of the brain from superior to inferior planes for both participant groups. To increase the signal-to-noise in these images, we used discrete frame averaging of images from each subject before the formation of parametric images (Reimold et al., 2004). The dynamic images were normalized to the SPM PET template (http://www.fil.ion.ucl.ac.uk/spm/). Average dynamic images weighted by the radiotracer dose were formed for each group. Average blood input functions were also formed from data of the participants in each group. Parametric images of model parameter λk3 were constructed using the method of Feng et al. (1996) for a two-tissue compartment irreversible model. A small amount of averaging to increase the signal-to-noise was allowed for local pixels using a method described previously (Logan et al., 2002). The average number of pixels grouped was on the order of 4.

Figure 3.

The mean ± SD of brain MAO A activity, λk3, in aggressive versus nonaggressive participants in cortical and subcortical regions. White triangles represent the mean for the aggressive group (n = 4), and black triangles represent the nonaggressive group (n = 5). *p < 0.05; **p < 0.01.