A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity

Psychiatry Res. 2000 Jul 24;95(1):9-23. doi: 10.1016/s0165-1781(00)00162-1.

Abstract

This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aggression / physiology*
  • Alleles
  • Brain / physiopathology*
  • Dinucleotide Repeats / genetics
  • Gene Expression Regulation, Enzymologic / physiology
  • Genes, Regulator / genetics*
  • Genotype
  • Hostility
  • Humans
  • Impulsive Behavior / genetics*
  • Impulsive Behavior / physiopathology
  • Male
  • Middle Aged
  • Minisatellite Repeats
  • Monoamine Oxidase / genetics*
  • Monoamine Oxidase / physiology
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / physiology
  • Serotonin / physiology

Substances

  • Receptors, Serotonin
  • Serotonin
  • Monoamine Oxidase