Neural mechanisms of genetic risk for impulsivity and violence in humans.
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.
Unit for Systems Neuroscience in Psychiatry, Neuroimaging Core Facility, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD 20892-1365, USA. andreasml@nih.gov
Andreas
A
Meyer-Lindenberg
Joshua W
JW
Buckholtz
Bhaskar
B
Kolachana
Ahmad
A
R Hariri
Lukas
L
Pezawas
Giuseppe
G
Blasi
Ashley
A
Wabnitz
Robyn
R
Honea
Beth
B
Verchinski
Joseph H
JH
Callicott
Michael
M
Egan
Venkata
V
Mattay
Daniel R
DR
Weinberger
D000483:Alleles; D004644:Emotions / Q000502:physiology; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008032:Limbic System / Q000033:anatomy & histology / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D009474:Neurons / Q000201:enzymology; D012306:Risk; D014754:Violence; D049951:X Chromosome Inactivation / Q000235:genetics
D008995:Monoamine Oxidase