Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys

Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
Biological Psychiatry (Impact Factor: 10.26). 02/2005; 57(2):167-72. DOI: 10.1016/j.biopsych.2004.10.012
Source: PubMed


Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences. We tested the hypothesis that a repeat polymorphism in the rhesus macaque MAOA gene promoter region influences aggressive behavior in male subjects.
Forty-five unrelated male monkeys raised with or without their mothers were tested for competitive and social group aggression. Functional activity of the MAOA gene promoter polymorphism was determined and genotypes scored for assessing genetic and environmental influences on aggression.
Transcription of the MAOA gene in rhesus monkeys is modulated by an orthologous polymorphism (rhMAOA-LPR) in its upstream regulatory region. High- and low-activity alleles of the rhMAOA-LPR show a genotype x environment interaction effect on aggressive behavior, such that mother-reared male monkeys with the low-activity-associated allele had higher aggression scores.
These results suggest that the behavioral expression of allelic variation in MAOA activity is sensitive to social experiences early in development and that its functional outcome might depend on social context.

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Available from: Jens Robert Wendland, Dec 26, 2013
    • "These variants have also been shown to participate in GxE interactions with early rearing experiences; for instance, male macaques raised with or without their mothers were found to exhibit competitive behavior and social group aggression in a MAOA-dependent fashion. In striking resemblance with the human data, carriers of low-activity alleles reared in small groups or without mothers were found to exhibit higher aggression and other anxiety-related maladaptive behaviors (Newman et al., 2005b;Karere et al., 2009). While no direct equivalent of uVNTR alleles exist in rodents, our group has begun studying the impact of early stress in a novel line of Maoa hypomorphic mice, generated through the insertion of a neomycin resistance cassette into the eighth intron of the Maoa gene (Bortolato et al., 2011). "
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    ABSTRACT: Drawing upon the recent resurgence of biological criminology, several studies have highlighted a critical role for genetic factors in the ontogeny of antisocial and violent conduct. In particular, converging lines of evidence have documented that these maladaptive manifestations of aggression are influenced by monoamine oxidase A (MAOA), the enzyme that catalyzes the degradation of brain serotonin, norepinephrine and dopamine. The interest on the link between MAOA and aggression was originally sparked by Han Brunner's discovery of a syndrome characterized by marked antisocial behaviors in male carriers of a nonsense mutation of this gene. Subsequent studies showed that MAOA allelic variants associated with low enzyme activity moderate the impact of early-life maltreatment on aggression propensity. In spite of overwhelming evidence pointing to the relationship between MAOA and aggression, the neurobiological substrates of this link remain surprisingly elusive; very little is also known about the interventions that may reduce the severity of pathological aggression in genetically predisposed subjects. Animal models offer a unique experimental tool to investigate these issues; in particular, several lines of transgenic mice harboring total or partial loss-of-function Maoa mutations have been shown to recapitulate numerous psychological and neurofunctional endophenotypes observed in humans. This review summarizes the current knowledge on the link between MAOA and aggression; in particular, we will emphasize how an integrated translational strategy coordinating clinical and preclinical research may prove critical to elucidate important aspects of the pathophysiology of aggression, and identify potential targets for its diagnosis, prevention and treatment.
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    • "Currently, however, only a few studies have investigated the effects of particular candidate genes on primate personality, respectively. In rhesus macaques (Macaca mulatta), playfulness and aggressiveness are influenced by length variations in the serotonin transporter gene (5-HTTLPR) (Barr et al., 2004) and MAOA gene (Newman et al., 2005). In vervet monkeys (Chlorocebus aethiops), an association between novelty seeking and the dopamine D4 receptor gene (DRD4) has been identified (Bailey et al., 2007), and chimpanzee (Pan troglodytes) neuroticism is associated with variation in the TPH2 gene (Hong et al., 2011). "
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    ABSTRACT: The importance of genes in regulating phenotypic variation of personality traits in humans and animals is becoming increasingly apparent in recent studies. Here we focus on variation in the vasopressin receptor gene 1a (Avpr1a) and oxytocin receptor gene (OXTR) and their effects on social personality traits in chimpanzees. We combine newly available genetic data on Avpr1a and OXTR allelic variation of 62 captive chimpanzees with individual variation in personality, based on behavioral assessments. Our study provides support for the positive association of the Avpr1a promoter region, in particular the presence of DupB, and sociability in chimpanzees. This complements findings of previous studies on adolescent chimpanzees and studies that assessed personality using questionnaire data. In contrast, no significant associations were found for the single nucleotide polymorphism (SNP) ss1388116472 of the OXTR and any of the personality components. Most importantly, our study provides additional evidence for the regulatory function of the 5' promoter region of Avpr1a on social behavior and its evolutionary stable effect across species, including rodents, chimpanzees and humans. Although it is generally accepted that complex social behavior is regulated by a combination of genes, the environment and their interaction, our findings highlight the importance of candidate genes with large effects on behavioral variation. Copyright © 2015. Published by Elsevier Inc.
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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.
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