Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity

Biol Psychiatry. 2006 Feb 15;59(4):334-40. doi: 10.1016/j.biopsych.2005.07.027. Epub 2005 Oct 3.

Abstract

Background: Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers.

Methods: We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging in 24 healthy men.

Results: Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmann's area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers.

Conclusions: These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Brain / physiology*
  • Brain Mapping
  • DNA / genetics
  • Genetic Variation
  • Genotype
  • Humans
  • Impulsive Behavior / genetics*
  • Impulsive Behavior / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Minisatellite Repeats
  • Monoamine Oxidase / genetics*
  • Oxygen / blood
  • Polymorphism, Genetic / genetics
  • Prefrontal Cortex / physiopathology
  • Visual Cortex / physiology

Substances

  • DNA
  • Monoamine Oxidase
  • Oxygen