MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma.
paper
Cited
Public
- Authors
- Weder, Natalie; Yang, Bao Zhu; Douglas-Palumberi, Heather; Massey, Johari; Krystal, John H; Gelernter, Joel; Kaufman, Joan
- Year
- 2009
- Journal
- Biological psychiatry
- PMID
- 18996506
- DOI
- 10.1016/j.biopsych.2008.09.013
- PMCID
- PMC3816252
BACKGROUND: Childhood adversity has been shown to interact with monoamine oxidase-A (MAOA) genotype to confer risk for antisocial behavior. Studies examining this gene-by-environment (G x E) association, however, have produced mixed results. METHODS: Relevant research is reviewed, and results of a study with 114 children (73 maltreated and 41 control subjects) are presented. The maltreated children represent the extreme on a continuum of adversity and were assessed at a time of extreme stress-shortly after removal from their parents' care due to abuse. Measures of aggressive behavior were obtained using standard research instruments, and monoamine oxidase-A MAOA genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled for using ancestral proportion scores computed on the basis of genotypes of ancestry informative markers. RESULTS: Many prior investigations appear to have had reduced power to detect the predicted G x E interaction because of low base rates of maltreatment and antisocial behavior in their samples and failure to use optimal procedures to control for population structure in ethnically diverse cohorts. In this investigation, a significant interaction was detected between exposure to moderate trauma and the "low-activity" MAOA genotype in conferring risk for aggression. Children with exposure to extreme levels of trauma, however, had high aggression scores regardless of genotype. CONCLUSIONS: Our study suggests that problems in aggressive behavior in maltreated children are moderated by MAOA genotype, but only up to moderate levels of trauma exposure. Extreme levels of trauma appear to overshadow the effect of MAOA genotype, especially in children assessed at time of acute crisis.
The low-activity MAOA gene (blue) was associated with increased aggression in the low to moderate range on the Trauma Exposure index. With Trauma Exposure Scores greater than this, genotype made no difference in childrenβs aggression scores (A). In predicting rule-breaking scores, only the Trauma Exposure Index was a significant predictor of childrenβs scores, with greater adversity associated with more rule-breaking behavior, regardless of genotype (B). There was a main effect for genotype and a GΓE interaction in predicting childrenβs inattention scores. Overall, higher inattention scores were associated with the low-activity version ofthe MAOA gene. At low to moderate levels of Trauma Exposure, higher inattention scores were associated with the low-activity version of the gene. At the most extreme level of Trauma Exposure, both genotypes were associated with high inattention scores, with the greatest scores observed in children with the high-activity MAOA gene (C). Analyses were conducted using the continuous Trauma Exposure scale. For illustrative purposes, children were grouped into low (N = 30), moderate (n = 14), severe (N = 42), and extreme (N = 28) categories, but analyses were conducted using the full TTES range of scores (0β9).
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