MAOA genotype, social exclusion and aggression: an experimental test of a gene-environment interaction.

In 2002, Caspi and colleagues provided the first epidemiological evidence that genotype may moderate individuals' responses to environmental determinants. However, in a correlational study great care must be taken to ensure the proper estimation of the causal relationship. Here, a randomized experiment was performed to test the hypothesis that the MAOA gene promoter polymorphism (MAOA-LPR) interacts with environmental adversity in determining aggressive behavior using laboratory analogs of real-life conditions. A sample of 57 Caucasian male students of Catalan and Spanish origin was recruited at the University of Barcelona. Ostracism, or social exclusion, was induced as environmental adversity using the Cyberball software. Laboratory aggression was assessed with the Point Subtraction Aggression Paradigm (PSAP), which was used as an analog of antisocial behavior. We also measured aggressiveness by means of the reduced version of the Aggression Questionnaire. The MAOA-LPR polymorphism showed a significant effect on the number of aggressive responses in the PSAP (F(1,53) = 4.63, P = 0.03, partial η(2) = 0.08), as well as social exclusion (F(1,53) = 8.03, P = 0.01, partial η(2) = 0.13). Most notably, however, we found that the MAOA-LPR polymorphism interacts significantly with social exclusion in order to provoke aggressive behavior (F(1,53) = 4.42, P = 0.04, partial η(2) = 0.08), remarkably, the low-activity allele of the MAOA-LPR polymorphism carriers in the ostracized group show significantly higher aggression scores than the rest. Our results support the notion that gene-environment interactions can be successfully reproduced within a laboratory using analogs and an appropriate design. We provide guidelines to test gene-environment interactions hypotheses under controlled, experimental settings.

[The development of antisocial behavior: psychobiological and environmental factors and gene-environment interactions]. / Desarrollo del comportamiento antisocial: factores psicobiológicos, ambientales e interacciones genotipo-ambiente.

INTRODUCTION: Antisocial behavior is a complex phenomenon with strong implications in neurology and psychiatry. In order to study the ontogenetic development of antisocial behavior, we must check for the existence of physiological mechanisms related to it, and to understand its environmentally-modulated functioning. AIM: To review the state-of-the-art of the development of antisocial behavior, and especially, of the interaction between environmental and genetic factors. DEVELOPMENT: Recent research has highlighted certain brain alterations linked to violent behavior, either at structural, or functional or biochemical levels. Genetic research has also made some advances in this field, discovering some genes--i.e. monoamineoxidase A (MAOA)--related to antisocial behavior. However, the importance of environmental factors in its development must not be left behind. Recent studies have shown that individuals carrying a low transcriptional activity allele of the MAOA gene, and that also suffered severe maltreatment are more prone to antisocial behavior. This interaction is biologically relevant, as there are underlying biological mechanisms that may be able to explain the ethiopathogeny of antisocial behavior. CONCLUSIONS: Although the works herein presented pioneered the field, they are limited by the fact that all the reviewed variables are associated to antisocial behavior, but they lack direct causal evidence of their effects on antisocial behavior. Undoubtedly, future research on psychobiological mechanisms and the understanding of their environmental modulation will help finding therapeutic targets and preventive strategies for antisocial behavior.

Desarrollo del comportamiento antisocial: factores psicobiológicos, ambientales e interacciones genotipo-ambiente / The deelopment of antisocial behavior: psychobiological and environmental factors and gene-environment interactions

Resumen. Introducción. El comportamiento antisocial es un fenómeno amplio y complejo con profundas implicaciones en neurología y psiquiatría. Para poder enfrentarse a una tarea tan compleja como estudiar el desarrollo ontogenético del comportamiento antisocial hace falta comprobar la existencia de mecanismos fisiológicos relacionados con él y entender cómo los factores ambientales pueden modular su funcionamiento. Objetivo. Revisar los conocimientos que tenemos acerca del desarrollo del comportamiento antisocial, y de la interacción entre factores ambientales y genéticos. Desarrollo. Investigaciones recientes han puesto de relieve alteraciones cerebrales que están asociadas al comportamiento violento, tanto desde el punto de vista estructural como funcional o bioquímico. La investigación genética también ha realizado avances en este terreno, como la detección de algunos genes –como el de la monoaminooxidasa A (MAOA)– relacionados con el comportamiento antisocial. Sin embargo, no debemos olvidar los factores ambientales en el desarrollo de éste. Estudios recientes indican que aquellos individuos portadores de una versión poco funcional del gen MAOA y que reciben un grave maltrato son más proclives al comportamiento antisocial. La significación biológica de esta interacción es relevante, ya que ciertos mecanismos biológicos subyacentes pueden explicar la etiopatogenia del comportamiento antisocial, aunque sea a un nivel muy elemental. Conclusiones. Los estudios mostrados, a pesar de ser pioneros, tienen una gran limitación, y es que a pesar de las evidencias de que todas las variables presentadas están asociadas al comportamiento antisocial, no hay una evidencia causal directa sobre su efecto en éste último. Sin duda, el estudio futuro de los mecanismos psicobiológicos y la comprensión de su modulación ambiental ofrecerán dianas terapéuticas y de prevención para el abordaje del comportamiento antisocial en todas sus vertientes (AU)

Summary. Introduction. Antisocial behavior is a complex phenomenon with strong implications in neurology and psychiatry. In order to study the ontogenetic development of antisocial behavior, we must check for the existence of physiological mechanisms related to it, and to understand its environmentally-modulated functioning. Aim. To review the state-of-the-art of the development of antisocial behavior, and especially, of the interaction between environmental and genetic factors. Development. Recent research has highlighted certain brain alterations linked to violent behavior, either at structural, or functional or biochemical levels. Genetic research has also made some advances in this field, discovering some genes –i.e. monoamineoxidase A (MAOA)– related to antisocial behavior. However, the importance of environmental factors in its development must not be left behind. Recent studies have shown that individuals carrying a low transcriptional activity allele of the MAOA gene, and that also suffered severe maltreatment are more prone to antisocial behavior. This interaction is biologically relevant, as there are underlying biological mechanisms that may be able to explain the ethiopathogeny of antisocial behavior. Conclusions. Although the works herein presented pioneered the field, they are limited by the fact that all the reviewed variables are associated to antisocial behavior, but they lack direct causal evidence of their effects on antisocial behavior. Undoubtedly, future research on psychobiological mechanisms and the understanding of their environmental modulation will help finding therapeutic targets and preventive strategies for antisocial behavior (AU)