Molecular genetics and antisocial behavior: Where do we stand?

Abstract

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.

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure

“…145,146 Also epistasis effects between gene variants have to be considered, for example between the 5-HTT, MAOA and DRD4 genes. [147][148][149] Epistasis effects between variants of the 5-HTT and BDNF genes have also been shown both in animal experiments (reviewed by, 150 and in humans regarding the degree of neuroticism. 151 For instance, Grabe et al 152 showed that, depending on the genotype of BDNF, which mediate neuronal plasticity, the 5-HTTLPR s allele showed either protective or risk properties with regard to depressive symptoms.…”

“…Also epistasis effects between gene variants have to be considered, for example between the 5‐HTT , MAOA and DRD4 genes . Epistasis effects between variants of the 5‐HTT and BDNF genes have also been shown both in animal experiments (reviewed by, and in humans regarding the degree of neuroticism .…”

Adolescent externalizing behaviour, psychological control, and peer rejection: Transactional links and dopaminergic moderation

“…Therefore we investigate longitudinal, transactional associations between behavioural problems and aspects of two different environments: psychological control for the family context and peer rejection for the peer context. Finally, GxE studies often adopt a candidate gene approach which underestimates the polygenic nature of complex behavioural outcomes such as externalizing problems (Iofrida, Palumbo, & Pellegrini, ). We use a biologically informed polygenic score including four polymorphisms within the dopamine system as a possible moderator.…”

Effects of behavioral genetic evidence on perceptions of criminal responsibility and appropriate punishment.

“…Two large twin studies estimated heritabilities of 37-57% for 5 kinds of aggressive behaviors (Yeh, Coccaro, & Jacobson, 2010), and 67% for antisocial behavior (Tuvblad, Narusyte, Grann, Sarnecki, & Lichtenstein, 2011). Work is ongoing to identify genes that may be linked to anti-social behavior, including monoamine oxidase A (MAOA), catechol-O-methyltransferase (COMT), dopamine transporter (DAT1), dopamine receptor (DRD2 and DRD 4), and serotonin transporter (5-HTTLPR) (Ferguson & Beaver, 2009; Iofrida, Plaumbo, & Pellegrini, 2014), although many of the findings remain a subject of contention (Vassos, Collier, & Fazel, 2014). It seems likely that data regarding genes associated with increased risk for criminal behavior will continue to appear (Tiihonen et al, 2014).…”