MAOA Genotype, Childhood Maltreatment, and Their Interaction in the Etiology of Adult Antisocial Behaviors

Haberstick, Brett C.; Lessem, Jeffrey M.; Hewitt, John K.; Smolen, Andrew; Hopfer, Christian J.; Halpern, Carolyn Tucker; Killeya‐Jones, Ley A.; Boardman, Jason D.; Tabor, Joyce W.; Siegler, Ilene C.; Williams, Redford B.; Harris, Kathleen Mullan

doi:10.1016/j.biopsych.2013.03.028

Cited by 85 publications

(52 citation statements)

References 52 publications

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“…As a matter of fact, most of the studies on the genetic association with antisocial behavior reached statistical significance in groups of individuals who had been subjected to child abuse and maltreatment, low parenting, maternal distress, and/or low socio-economic status. 13,78,[125][126][127]140 On the other hand, previous G Â E association studies demonstrating that single gene variants in combination with the adverse environment are associated to aggression and conduct disorders, like the groundbreaking work of Caspi and colleagues on MAOA uVNTR, 7 failed to be replicated in larger samples of individuals by very recent publications, 49,50 raising again some doubts about such an association.…”

Section: Discussionmentioning

confidence: 99%

“…28 A number of subsequent studies confirmed these results, 29,31,[37][38][39][40][41][42][43][44][45] while others failed to replicate them. [46][47][48][49][50] Among these papers, two meta-analyses, published in 2006 and 2007, strongly supported the original hypothesis, 40,41 while two very recent studies published in 2013 and conducted in very large samples did not replicate these previous findings. In detail, as part of the Pelotas 1993 Birth Cohort Study, Kieling and colleagues tested 1998 adolescent males from low-and middle-income countries for the interaction between MAOA uVNTR genotype and childhood maltreatment in the occurrence of ''externalizing behavior,'' that is a behavior which comprises most antisocial traits including aggression, and represents a major risk factor for later juvenile delinquency, adult crime, and violence.…”

Section: Introductionmentioning

confidence: 88%

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Molecular genetics and antisocial behavior: Where do we stand?

Iofrida

Palumbo

Pellegrini

2014

Exp Biol Med (Maywood)

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Over the last two decades, it has become increasingly evident that control of aggressive behavior is modulated by the individual genetic profile as well. Several candidate genes have been proposed to play a role in the risk to develop antisocial behavior, and distinct brain imaging studies have shown that specific cortical areas may be functionally and/or structurally impaired in impulsive violent subjects on the basis of their genotypes. In this paper, we review the findings regarding four polymorphisms-MAOA (Monoamine oxidase A) uVNTR, SLC6A4 (solute carrier family 6 (neurotransmitter transporter), member 4) 5HTTLPR, COMT (Catechol-O-methyltransferase) Val158Met and DRD4 (dopamine D4 receptor) VNTR 1-11-that all have been found to be associated with an increased vulnerability for antisocial and impulsive behavior in response to aversive environmental conditions. These results, however, have not been replicated by other studies, likely because of crucial methodological discrepancies, including variability in the criteria used to define antisocial behavior and assessment of environmental factors. Finally, it has been recently proposed that these genetic variants may actually increase the individual susceptibility not merely to the negative environmental factors, but to the positive ones as well. In this view, such alleles would play a wider modulatory role, by acting as "plasticity" rather than "vulnerability" genes. Overall, these findings have potential important implications that span well outside of neuroscience and psychiatry, to embrace ethics, philosophy, and the law itself, as they pose new challenges to the very notion of Free Will. Novel properly controlled studies that examine multi-allelic genetic profiles, rather than focusing on distinct single variants, will make it possible to achieve a clearer understanding of the molecular underpinnings of the nature by nurture interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Molecular genetics and antisocial behavior: Where do we stand?

Iofrida

Palumbo

Pellegrini

2014

Exp Biol Med (Maywood)

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“…The most recent meta-analysis reported that early adversity predicted antisocial outcomes more strongly for low, relative to high, activity MAOA genotype (p = .0044), with the interaction being particularly pronounced for maltreatment (p = .0000008). However, the findings could not be confirmed in all samples (e.g., Kieling et al 2013;Haberstick et al 2014), leaving room for ambiguity. In female subjects, findings suggested differential interaction patterns.…”

Section: Introductionmentioning

confidence: 85%

Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood

et al. 2016

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Findings on the etiology of aggressive behavior have provided evidence for an effect both of genetic factors, such as variation in the monoamine oxidase A (MAOA) gene, and adverse environmental factors. Recent studies have supported the existence of gene × environment interactions, with early experiences playing a key role. In the present study, the effects of prenatal nicotine exposure, MAOA genotype and their interaction on aggressive behavior during young adulthood were examined. In a sample of 272 young adults (129 males, 143 females) from an epidemiological cohort study, smoking during pregnancy was measured with a standardized parent interview at the offspring's age of 3 months. Aggressive behavior was assessed between the ages of 19 and 25 years using the Young Adult Self-Report. DNA was genotyped for the MAOA 5' untranslated region variable number of tandem repeats polymorphism (VNTR). Results revealed a significant interaction between MAOA and smoking during pregnancy, indicating higher levels of aggressive behavior in young adults carrying the MAOA low-expressing genotype who had experienced prenatal nicotine exposure (n = 8, p = .025). In contrast, in carriers of the MAOA high-expressing genotype, maternal smoking during pregnancy had no effect on aggressive behavior during young adulthood (n = 20, p = .145). This study extends earlier findings demonstrating an interaction between MAOA genotype and prenatal nicotine exposure on aggressive behavior into young adulthood. The results point to the long-term adverse effects of smoking during pregnancy on the offspring's mental health, possibly underlining the importance of smoking cessation during pregnancy. According to the nature of the study (particularly sample size and power), analyses are exploratory and results need to be interpreted cautiously.

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“…10 However, the largest study on this issue, with more than 4000 individuals, could not confirm the hypothesis that this MAOA genotype moderates the relationship between childhood maltreatment and antisocial behavior, but found statistically non-significant evidence for a main effect of MAOA genotype on having disposition toward violence. 11 Thus, the issue of a ‘warrior gene’ has remained controversial.…”

Section: Introductionmentioning

confidence: 99%

Genetic background of extreme violent behavior

et al. 2014

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In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

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MAOA Genotype, Childhood Maltreatment, and Their Interaction in the Etiology of Adult Antisocial Behaviors

Cited by 85 publications

References 52 publications

Molecular genetics and antisocial behavior: Where do we stand?

Molecular genetics and antisocial behavior: Where do we stand?

Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood

Genetic background of extreme violent behavior

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