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.

Download full-text


Available from: Jens Robert Wendland, Dec 26, 2013
1 Follower
38 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Hormones and Behavior 08/2015; 75. DOI:10.1016/j.yhbeh.2015.08.006 · 4.63 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Genome 10/2014; 57(8):1-6. DOI:10.1139/gen-2014-0065 · 1.42 Impact Factor
  • Source
    • "In these studies, candidate genes are selected based on what is known in humans so as to establish the rhesus monkey as a reliable model for the study of the trait or pathology of interest. The most commonly studied genes in monkeys are those which genetic studies have identified as functionally equivalent genetic single nucleotide polymorphisms (SNPs) in rhesus monkeys to those found in humans, including the serotonin-transporter-linked polymorphic region (5-HTTLPR; Lesch et al. 1997), the µ-opioid receptor (OPRM1; Miller et al. 2004), the monoamine oxidase A (MAOA) gene promoter (Newman et al. 2005), and the corticotropin releasing hormone (CRH) promoter (Barr et al. 2008) and the brain-derived neurotrophic factor (BDNF) gene (Cirulli et al. 2011). Further research has expanded on the identification of these SNPs by genotyping individual subjects using DNA isolated from blood samples and associating particular genotypes with behaviors of interest (see Part II, below). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This report reviews the scientific literature from the past several decades that focuses on nonhuman primates (NHPs) as models of neuropsychiatric disorders, including anxiety, and alcoholism. In particular, we highlight the approaches, advantages, and disadvantages of the rearing, genetic, and epigenetic methodologies behind these studies as a means of evaluating the application of these methods in assessing disorders in NHPs as models of human disease. Finally, we describe the contributions the NHP studies have made to neuropsychiatric research and areas for future research.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):361-70. DOI:10.1093/ilar/ilu025 · 2.39 Impact Factor
Show more