Brain Monoamine Oxidase A Activity Predicts Trait Aggression

Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 06/2008; 28(19):5099-104. DOI: 10.1523/JNEUROSCI.0925-08.2008
Source: PubMed


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.

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    • "Integration of these results is complicated by variation in methods and measures across groups; however, three meta-analyses—the most recent and largest of which included 20 studies involving male subjects with over 5,800 participants—support the association between MAOA and antisocial behavior by maltreated boys (Byrd & Manuck, 2014; Kim-Cohen et al., 2006; Taylor & Kim-Cohen, 2007). 1 Further supporting this finding, the same gene– environment interaction was found to be associated with symptoms of antisocial personality disorder (Beach et al., 2010). Mechanisms for the differential effects of MAOA alleles are currently being elucidated (Alia-Klein et al., 2008; Buckholtz & Meyer- Lindenberg, 2014). Within only a few years of the initial report of a link between MAOA and antisocial behavior in humans, the legal profession was aware of the data and beginning to explore their implications for the criminal justice system. "
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    ABSTRACT: Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants' responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants' apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants' decisions. Moreover, participants' beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition.
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    • "Human genomes contain VNTRs within the 5= untranslated region (UTR) of the monoamine oxidase A (MAOA) gene, which are 30 bp in length with tandem repeats of three, four, or five (Sabol et al. 1998). Expression of the MAOA gene is related to aggressive character and behavior (Lawson et al. 2003; Newman et al. 2005; Wendland et al. 2006b; Alia-Klein et al. 2008), and the MAOA VNTR polymorphism in the 5= UTR region affects its transcription (Deckert et al. 1999). Connection studies between MAOA VNTR polymorphisms and the transcriptional regulation of the MAOA gene have been reported in humans (Beach et al. 2010; Guo et al. 2008; Pai et al. 2007). "
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    ABSTRACT: Variable number of tandem repeats (VNTRs) are scattered throughout the primate genome, and genetic variation of these VNTRs have been accumulated during primate radiation. Here, we analyzed VNTRs upstream of the monoamine oxidase A (MAOA) gene in 11 different gibbon species. An abundance of truncated VNTR sequences and copy number differences were observed compared to those of human VNTR sequences. To better understand the biological role of these VNTRs, a luciferase activity assay was conducted and results indicated that selected VNTR sequences of the MAOA gene from human and three different gibbon species (Hylobates klossii, Hylobates lar, and Nomascus concolor) showed silencing ability. Together, these data could be useful for understanding the evolutionary history and functional significance of MAOA VNTR sequences in gibbon species.
    Full-text · Article · Oct 2014 · Genome
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    • "Alia-Klein et al72 confirmed the functional relevance of the MAOA enzyme by showing moderate negative correlations of brain MAOA activity with trait aggression. However, no differences in enzymatic activity were found regarding genotype, in line with other research failing to find such relationship.73 "
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    ABSTRACT: Hereditary factors are increasingly attracting the interest of behavioral scientists and practitioners. Our aim in the present article is to introduce some state-of-the-art topics in behavioral genetics, as well as selected findings in the field, in order to illustrate how genetic makeup can modulate the impact of environmental factors. We focus on the most-studied polymorphism to date for antisocial responses to adversity: the monoamine oxidase A gene. Advances, caveats, and promises of current research are reviewed. We also discuss implications for the use of genetic information in applied settings.
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