Neural mechanisms of genetic risk for impulsivity and violence in humans
Open accessAbstract
Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.
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The MAO-A allele is associated with diminished brain circuitry related to impulse control that would promote aggression.
“The MAO-A allele is associated with diminished brain circuitry related to impulse control that would promote aggression.”
From Mediators and Mechanisms of Change in Psychotherapy Research (2007) · cites this paper as Meyer-Lindenberg et al. 2006
The paper reports that the low-expression MAOA allele is associated with impaired cingulate activation during cognitive inhibition and with increased risk of violent behavior (opening summary; page not supplied). Its Discussion proposes that impaired emotional or cognitive control may contribute to violence, but does not establish that the circuitry change would promote aggression. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRecent findings show neural mechanisms through which the genetic influence is likely to operate.
“For example, recent findings show the neural mechanisms through which the genetic influence is likely to operate (Meyer-Lindenberg et al. 2006).”
From Mediators and Mechanisms of Change in Psychotherapy Research (2007) · cites this paper as Meyer-Lindenberg et al. 2006
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- Authors
- Meyer-Lindenberg, A., Buckholtz, J. W., Kolachana, B., R. Hariri, A., Pezawas, L., Blasi, G., Wabnitz, A., Honea, R., Verchinski, B., Callicott, J. H., Egan, M., Mattay, V., & Weinberger, D. R.
- Affiliations
- *Unit for Systems Neuroscience in Psychiatry,
- National Institutes of Health (US)
- Neuroimaging Core Facility, and
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-04-18
- Volume
- 103
- Issue
- 16
- Pages
- 6269-6274
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2132089117
- Cited by
- 876
- References
- 10
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 18 · 2023: 6 · 2022: 12 · 2021: 39 · 2020: 44 · 2019: 49 · 2018: 38 · 2017: 34 · 2016: 35 · 2015: 51 · 2014: 60 · 2013: 54 · 2012: 58
- FWCI
- 26.95
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- MAOA gene, monoamine oxidase A, impulsivity, aggression, violence, X-linked polymorphism, X chromosome inactivation, limbic system, orbitofrontal cortex, hippocampus, prefrontal cortex, emotion regulation, cognitive control, cognitive inhibition, genetic risk
- MeSH terms
- Alleles, Emotions, Gene Frequency, Genotype, Humans, Limbic System, Male, Monoamine Oxidase, Neurons, Risk, Violence, Gene Expression, X Chromosome Inactivation
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