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Cited by 46Neurotransmitter Receptor Influence on BehaviorPsychopathy, Forensic Psychiatry, Sexual OffendingNeuroendocrine regulation and behavior

Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder

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Philibert, Robert A., Wernett, Pamela, Plume, Jeff, Packer, Hans, Brody, Gene H., Beach, Steven R.H.·2011·Biological Psychology
DOI 10.1016/j.biopsycho.2011.04.007PMC PMC3134149
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Abstract

Monoamine Oxidase A (MAOA) is a critical enzyme in the catabolism of monoaminergic neurotransmitters. MAOA transcriptional activity is thought to be regulated by a well characterized 30 base pair (bp) variable nucleotide repeat (VNTR) that lies approximately ∼1000 bp upstream of the transcriptional start site (TSS). However, clinical associations between this VNTR genotype and behavioral states have been inconsistent. Herein, we describe a second, 10 bp VNTR that lies ∼1500 bp upstream of the TSS. We provide in vitro and in silico evidence that this new VNTR region may be more influential in regulating MAOA transcription than the more proximal VNTR and that methylation of this CpG-rich VNTR is genotype dependent in females. Finally, we demonstrate that genotype at this new VNTR interacts significantly with history of child abuse to predict antisocial personality disorder (ASPD) in women and accounts for variance in addition to that explained by the prior VNTR.

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  • Nine-repeat carriers (lower risk allele) of the 10 bp MAOA VNTR show lower methylation level in the MAOA promoter in females.

    “nine-repeat (9R) carriers (the lower risk allele) of the 10 bp MAOA VNTR show a lower methylation level in the MAOA promoter in females (129).”

    From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [129]

    The Results report significantly lower MAOA promoter-associated methylation in female 9R/9R subjects than in females with a 10R allele. This does not establish lower methylation for all 9R carriers, including 9R/10R heterozygotes. The Results also associate the 10R allele with greater vulnerability to childhood maltreatment, so the description of 9R as lower risk is supported in that context, not as an unqualified risk designation. (LLM, conf=0.88)

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  • A VNTR comprising CCCCTCCCCG (A repeat) and CTCCTCCCCG (B repeat) of a 10-base pair unit near the transcription start site of MAOA contributes to antisocial behavior after exposure to childhood trauma in females.

    “There is a VNTR comprising CCCCTCCCCG (known as the “A repeat”) and CTCCTCCCCG (known as the “B repeat”) of a 10-base pair unit near the transcription start site (TSS) of MAOA that contributes to antisocial behavior after exposure to childhood trauma in females (129).”

    From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [129]

    The Results (page unavailable) identify the A and B decamer repeats and report that, in women, MAOA P2 genotype interacted with a history of child abuse to predict symptoms of antisocial personality disorder. The claim broadens those measured outcomes and exposures to antisocial behavior and childhood trauma generally; the paper does not establish those broader claims or a causal contribution. (LLM, conf=0.84)

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Research works printed but not linked: 2

  1. American Psychiatric Association 1987 Diagnostic and Statistics Manual of Mental Disorders, Version III-Revised American Psychiatric Press Washington DC
  2. Philibert RA Beach SR Gunter TD Brody GH Madan A Gerrard M 2010 The effect of smoking on MAOA promoter methylation in DNA prepared from lymphoblasts and whole blood Am J Med Genet B Neuropsychiatr Genet 153B 619 628 19777560 PMC3694401

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Authors
Philibert, R. A., Wernett, P., Plume, J., Packer, H., Brody, G. H., & Beach, S. R. H.
Affiliations
  • University of Iowa (US)
  • University of Georgia (US)
Corresponding author
Philibert, Robert A.
ORCID
Venue
Biological Psychology
Publisher
Elsevier BV
Published
2011-07
Volume
87
Issue
3
Pages
366-371
ISSN
0301-0511 (ISSN-L)
DOI
10.1016/j.biopsycho.2011.04.007
PMC
PMC3134149
OpenAlex
W2096963490
Cited by
46
References
42
Citations by year
2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 4 · 2012: 4
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (MH080898, R01MH080898)
  • National Institute on Drug Abuse (R01DA015789, P30DA027827, DA015789)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
monoamine oxidase A, antisocial personality disorder, variable number tandem repeats, enhancers, gene-environment interaction, child abuse, DNA methylation, CpG methylation, sex differences, women, gene expression regulation
MeSH terms
Adult, Alleles, Antisocial Personality Disorder, Female, Gene Expression Regulation, Genotype, Humans, Male, Middle Aged, Monoamine Oxidase, Promoter Regions, Genetic, Polymorphism, Single Nucleotide

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