Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

Transl Psychiatry. 2012 Feb 28;2(2):e85. doi: 10.1038/tp.2012.7.


A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene-brain-behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ~6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aggression / physiology*
  • Alleles*
  • Brain / physiopathology*
  • Child
  • Child Behavior Disorders / genetics*
  • Child Behavior Disorders / physiopathology
  • Chromosome Banding
  • Chromosomes, Human, X / genetics
  • Dopamine / physiology*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine beta-Hydroxylase / genetics
  • Endophenotypes
  • Female
  • Genetic Association Studies*
  • Humans
  • Internal-External Control
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term / physiology*
  • Monoamine Oxidase / genetics*
  • Nerve Net / physiopathology
  • Oxygen / blood
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Dopamine D4 / genetics
  • Receptors, Dopamine D5 / genetics
  • Risk Factors
  • Young Adult


  • DRD5 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human
  • Receptors, Dopamine D4
  • Receptors, Dopamine D5
  • Dopamine beta-Hydroxylase
  • Monoamine Oxidase
  • Oxygen
  • Dopamine