Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour: current and future directions

J Neural Transm (Vienna). 2018 Nov;125(11):1601-1626. doi: 10.1007/s00702-018-1892-2. Epub 2018 Jun 7.


Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene-environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed.

Keywords: Antisocial personality disorder; Brunner syndrome; Conduct disorder; Genetic association studies; Genetic susceptibility; Gene–environment interaction; Juvenile delinquency; Monoamine oxidase A; Review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Antisocial Personality Disorder / etiology*
  • Antisocial Personality Disorder / genetics
  • Antisocial Personality Disorder / psychology
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Juvenile Delinquency / psychology*
  • Monoamine Oxidase / genetics*
  • Polymorphism, Single Nucleotide*
  • Social Environment*


  • Monoamine Oxidase