Molecular genetics and antisocial behavior: where do we stand?
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.
Laboratory of Molecular Biology, Department of Surgical, Medical and Molecular Pathology and of Critical Care, University of Pisa, Pisa I-56126, Italy.
Caterina
C
Iofrida
Laboratory of Molecular Biology, Department of Surgical, Medical and Molecular Pathology and of Critical Care, University of Pisa, Pisa I-56126, Italy.
Sara
S
Palumbo
Laboratory of Molecular Biology, Department of Surgical, Medical and Molecular Pathology and of Critical Care, University of Pisa, Pisa I-56126, Italy silvia.pellegrini@med.unipi.it.
Silvia
S
Pellegrini
D000987:Antisocial Personality Disorder / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004198:Disease Susceptibility; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D008995:Monoamine Oxidase / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
C493599:DRD4 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
COMT; DRD4; MAOA; SLC6A4; antisocial behavior; molecular biology