9.3 Monoamine oxidase A, maltreatment during childhood and later violence
One Dutch family was found to have a history of antisocial (aggressive) behaviour. Genetic studies were conducted and a potential culprit gene MAOA, monoamine oxidase A, identified. The aggressive individuals in the family appeared to have a mutant gene which produced no MAOAP, an enzyme involved in the breakdown of certain neurotransmitters, including serotonin. A knockout mouse model, in which the MAOA gene was inactive, was also found to be aggressive, apparently confirming the role of MAOAP in aggression. However, surveys have shown that not all people showing antisocial behaviour have the mutant gene or abnormal levels of MAOAP.
In parallel with these genetic studies of human aggression, the role of childhood maltreatment as a risk factor in later antisocial behaviour has been studied. Boys who experience abuse, e.g. punitive parenting, are at risk of developing into violent offenders. The abuse increases the risk of later criminality by about 50 per cent. However, most maltreated children do not become violent adults. Just as with the MAOA study above, there is no clear cause and effect relationship.
Terrie Moffitt and Avshalom Caspi and colleagues at the Institute of Psychiatry in London wondered if these two factors, a mutant MAOA allele and maltreatment during childhood, might work in tandem in some way. Moffitt and Caspi turned to the Dunedin Multidisciplinary Health and Development Study underway in New Zealand to test their hypothesis. The Dunedin study has tested a cohort of 1037 people, born in 1972, approximately every two years, with the cohort remaining virtually intact (96 per cent), even after 26 years. The study had collected data on early childhood maltreatment and on aggressive behaviour as adolescents and young adults. All Moffitt and Caspi had to do was determine the MAOA alleles carried by the individuals in the cohort (Caspi et al., 2002). (They tested only the 442 individuals who fitted their selection criteria.)
The hypothesis they were testing was that individuals who had both childhood maltreatment and mutant MAOA would be more likely to exhibit antisocial behaviour than individuals who had childhood maltreatment but normal MAOA or no childhood maltreatment and mutant MAOA. One result is presented in Figure 23.
In Figure 23 histograms (a) to (d) all show effects on antisocial behaviour in adulthood. (a) Effect of normal MAOA and mutant MAOA, (b) effect of the absence of maltreatment and severe maltreatment during childhood, (c) combined effect of the absence of childhood maltreatment and either normal MAOA, or mutant MAOA, (d) combined effect of severe childhood maltreatment and either normal MAOA or mutant MAOA. Zero represents the mean level of antisocial behaviour of the people studied: values further away from the mean, above 0, represent higher levels of antisocial behaviour; values further away from the mean, below 0, represent lower levels of antisocial behaviour.
When the sample of individuals is divided into two groups on the basis of their MAOA alleles, and their antisocial behaviour indexes compared, no significant differences emerge (Figure 23a).
What does this result mean in terms of the gene of interest and antisocial behaviour?
The result means that the gene of interest does not, of itself, cause antisocial behaviour.
When the sample of individuals is divided into a no childhood maltreatment group and a severe childhood maltreatment group, and their antisocial behaviour indexes compared, a significant difference is found (Figure 23b).
What does this result mean in terms of childhood maltreatment and adult antisocial behaviour?
The result means that severe childhood maltreatment often causes adult antisocial behaviour.
The histogram in Figure 23c shows that in the absence of childhood maltreatment, antisocial adult behaviour is unlikely to occur, irrespective of whether individuals have normal MAOA or mutant MAOA.
What does the histogram in Figure 23d show?
Figure 23 shows that those individuals who endure severe childhood maltreatment show significantly less antisocial behaviour as adults if they also have normal MAOA. Conversely, those individuals who endure severe childhood maltreatment show significantly more antisocial behaviour as adults if they also have mutant MAOA.
The data clearly show what the authors refer to as a protective effect against childhood maltreatment of normal MAOA.
What do these data reveal about how the gene MAOA and the environmental factor childhood maltreatment affect development?
These data reveal very clearly the interaction between environmental factors and genetic factors in determining later behaviour.
These data do not reveal in any way that antisocial behaviour is a genetic disease. However, they begin to unravel the complex interplay between genes and environment and perhaps shed light on those who are at risk of developing antisocial behaviour