Frequency of 3’ VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior

Черепкова, Е. В.; Aftanas, Lyubomir I.; Максимов, Н. И.; Menshanov, Petr N.

doi:10.1007/s10517-016-3551-7

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…Two hundred individuals were asked to respond to fifty-six moral dilemmas, each one proposing to adopt an utilitarian choice, that is, to sacrifice a person in order to save a larger group of people. Behavioral responses were analyzed in respect to five alleles of genes that regulate dopaminergic neurotransmission and that, taken individually, are known to affect behavioral and personality traits in humans (Balestri et al, 2014 ; Iofrida et al, 2014 ; Cherepkova et al, 2016 ; Heinrich et al, 2016 ). As the five selected genetic variants were all located in genes belonging to the same biological pathway, they were considered to act synergistically.…”

Section: Discussionmentioning

confidence: 99%

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study

Pellegrini

Palumbo

Iofrida

et al. 2017

Front. Behav. Neurosci.

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Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment. Moreover, while it is well-known that responses to the same moral dilemmas differ across individuals, to what extent this variability may be rooted in genetics still remains to be understood. As dopamine is a key modulator of neural processes underlying executive functions, we questioned whether genetic polymorphisms associated with decision-making and dopaminergic neurotransmission modulation would contribute to the observed variability in moral judgment. To this aim, we genotyped five genetic variants of the dopaminergic pathway [rs1800955 in the dopamine receptor D4 (DRD4) gene, DRD4 48 bp variable number of tandem repeat (VNTR), solute carrier family 6 member 3 (SLC6A3) 40 bp VNTR, rs4680 in the catechol-O-methyl transferase (COMT) gene, and rs1800497 in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene] in 200 subjects, who were requested to answer 56 moral dilemmas. As these variants are all located in genes belonging to the dopaminergic pathway, they were combined in multilocus genetic profiles for the association analysis. While no individual variant showed any significant effects on moral dilemma responses, the multilocus genetic profile analysis revealed a significant gender-specific influence on human moral acceptability. Specifically, those genotype combinations that improve dopaminergic signaling selectively increased moral acceptability in females, by making their responses to moral dilemmas more similar to those provided by males. As females usually give more emotionally-based answers and engage the “emotional brain” more than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.

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Section: Discussionmentioning

confidence: 99%

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study

Pellegrini

Palumbo

Iofrida

et al. 2017

Front. Behav. Neurosci.

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“…The DRD4 gene includes in its 3rd exon a variable region with 2 to 11 repeats with 48 base pair length, the highest linking ability of the receptor is observed for 4 repeats, whereas expression level decreases significantly for 7 repeats (VanNess et al, 2005). It was found in course of studying aggressive and antisocial behavior that the*7R repeats were more often encountered in people convicted for violent crimes (Cherepkova et al, 2016), especially the ones, who experienced stress factors in their childhood (Schlomer et al, 2015). At the same time, it was shown for the Russian sample of inmates that the *5R allele carriers also demonstrated high aggression levels similar to those of the*7R allele carriers (Cherepkova et al, 2015), which agrees with the data on identical functional changes in the DRD4 receptor with 5 or 7 repeats (Takeuchi et al, 2015).…”

Section: Molecular-genetic Markers Of Predisposition Towards Aggressimentioning

confidence: 99%

“…Tandem repeat of VNTR40 (from 3 to 11 times) is found in the SLC6A3 gene, however, the presence of a link between the repeat count and gene expression activity remains unconfirmed. Numerous papers show associations between the *10R allele (Cherepkova et al, 2016), as well as the*9R allele (Qadeer et al, 2017), and antisocial behavior. Furthermore, the association between the*9R allele and increased aggressiveness was earlier confirmed by the longitudinal twin study (Young et al, 2002).…”

Section: Molecular-genetic Markers Of Predisposition Towards Aggressimentioning

confidence: 99%

Recent advances in genetics of aggressive behavior

Davydova¹,

Litvinov²,

Enikeeva³

et al. 2018

Vestn. VOGiS

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One of the most important problems of modern neurobiology and medicine is an understanding of the mechanisms of normal and pathological behavior of a person. Aggressive behavior is an integral part of the human psyche. However, environmental risk factors, mental illness and somatic diseases can lead to increased aggression to be the biological basis of antisocial behavior in a human society. An important role in development of aggressive behavior belongs to the hereditary factors that may be linked to abnormal functioning of neurotransmitter systems in the brain yet the underlying genetic mechanisms remain unclear, which is due to a large number of single nucleotide polymorphisms, insertions and deletions in the structure of genes that encode the components of the neurotransmitter systems. The most studied candidate genes for aggressive behavior are serotonergic (TPH1, TPH2, HTR2A, SLC6A4) and dopaminergic (DRD4, SLC6A3) system genes, as well as the serotonin or catecholamine metabolizing enzyme genes (COMT, MAOA). In addition, there is evidence that the hypothalamic-pituitary system genes (OXT, OXTR, AVPR1A, AVPR1B), the sex hormone receptors genes (ER1, AR), neurotrophin (BDNF) and neuronal apoptosis genes (CASP3, BAX) may also be involved in development of aggressive behavior. The results of Genome-Wide Association Studies (GWAS) have demonstrated that FYN, LRRTM4, NTM, CDH13, DYRK1A and other genes are involved in regulation of aggressive behavior. These and other evidence suggest that genetic predisposition to aggressive behavior may be a very complex process.

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“…CU traits have been shown to be highly heritable (on the order of 0.80; Viding et al 2008) and are presumed to be a function of polygenic liability (Dick et al 2011; Rautiainen et al 2016; Tielbeek et al 2017). Candidate gene studies involving common allelic variation in the serotonin transporter gene SLC6A4 (Sadeh et al 2010; Cherepkova et al 2016), the COMT gene (located in the 22q11 region outside of the duplication carried by this patient), and the MAOA gene have shown significant, if inconsistent, associations with antisocial outcome (Fowler et al 2009; Hirata et al 2013). Rare variants in MAOA have been associated with aggression (Brunner et al 1993), but we are not aware of any prior report of rare variants associated with extreme CU traits.…”

Section: Introductionmentioning

confidence: 99%

22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy

Vyas

Constantino

Baldridge

2019

Cold Spring Harb Mol Case Stud

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Callous-unemotional (CU) traits are highly disabling behavioral characteristics, common predictors of delinquency and criminality, and pathognomonic for antisocial personality disorder. They are highly heritable, but their specific molecular genetic causes are unknown. Here, we briefly review the literature on neuropsychiatric correlates of 22q11.2 duplication and describe a newly identified case of a 737-kb microduplication within the low copy repeat (LCR) B-D region, involving a 13-yr-old early adoptee with mild developmental delay and severe, chronic antisocial behavior of early childhood onset. When psychiatric symptoms have been reported in relation to duplications in this specific region, 19% of the reports feature aggression—but never previously CU traits—as a component of the phenotype. We discuss the potential implications of gain of function in this chromosomal region for heritable origins of sociopathy and their possible relation to genetic influences on aggression.

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Frequency of 3’ VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior

Cited by 5 publications

References 13 publications

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study

Recent advances in genetics of aggressive behavior

22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy

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