Test of association between 10 single nucleotide polymorphisms in the oxytocin receptor gene and conduct disorder

Sakai, Joseph T.; Crowley, Thomas J.; Stallings, Michael C.; McQueen, Matthew B.; Hewitt, John K.; Hopfer, Christian J.; Hoft, Nicole R.; Ehringer, Marissa A.

doi:10.1097/ypg.0b013e32834c0cb2

Cited by 19 publications

(15 citation statements)

References 34 publications

(38 reference statements)

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“…A main effect of OXTR on aggression has implications for OXTR 's role in the etiology of disorders of which aggression is a core feature and for the consideration of aggression and related social behavior as behavioral dimensions. OXTR has been found to show no association with conduct disorder after correcting for the number of SNPs tested in one study [Sakai et al, ] and has not been investigated in relation to antisocial personality disorder, borderline personality disorder, oppositional defiant disorder, or intermittent‐explosive disorder. Nevertheless, OXTR 's influence on aggression may cut across these disorders and partially explain the etiology of an aggressive behavioral dimension that is more reliably measured and etiologically simple than the more complex traditional diagnostic categories.…”

Section: Discussionmentioning

confidence: 99%

Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression

LoParo

Johansson

Walum

et al. 2015

American J of Med Genetics Pt B

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Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (r GE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition.

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Section: Discussionmentioning

confidence: 99%

Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression

LoParo

Johansson

Walum

et al. 2015

American J of Med Genetics Pt B

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“…The genes for the serotonergic receptors HTR1B and HTR2A have been associated with CD and CU [Jensen et al, 2009;Moul et al, 2013]. Several variants within the OXTR gene have been associated with CD and CU Malik et al, 2012;Sakai et al, 2012;Dadds et al, 2014;Smearman et al, 2015]. Also, associations have been described for BDNF with ODD and CU [Willoughby et al, 2013].…”

Section: Candidate Genes Studied In Children and Adolescentsmentioning

confidence: 99%

Genetics of aggressive behavior: An overview

Veroude

Zhang‐James

Fernàndez‐Castillo

et al. 2015

American J of Med Genetics Pt B

118

107

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The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative.

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“…Psychological processes that are disturbed in psychopathy, i.e., emotion recognition, empathy, and social affiliation, are all influenced by oxytocin signaling. However, apart from a few candidate gene studies associating OXTR SNPs with conduct problems or CU traits (Beitchman et al, 2012; Sakai et al, 2012), empirical evidence is scarce. Dadds et al (in press) provide first evidence that OXTR promoter methylation is associated with CU traits in males.…”

Section: Callous-unemotional Traitsmentioning

confidence: 99%

Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience

Kumsta¹,

Hummel²,

Chen³

et al. 2013

Front. Neurosci.

169

124

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Genetic approaches have improved our understanding of the neurobiological basis of social behavior and cognition. For instance, common polymorphisms of genes involved in oxytocin signaling have been associated with sociobehavioral phenotypes in healthy samples as well as in subjects with mental disorders. More recently, attention has been drawn to epigenetic mechanisms, which regulate genetic function and expression without changes to the underlying DNA sequence. We provide an overview of the functional importance of oxytocin receptor gene (OXTR) promoter methylation and summarize studies that have investigated the role of OXTR methylation in behavioral phenotypes. There is first evidence that OXTR methylation is associated with autism, high callous-unemotional traits, and differential activation of brain regions involved in social perception. Furthermore, psychosocial stress exposure might dynamically regulate OXTR. Given evidence that epigenetic states of genes can be modified by experiences, especially those occurring in sensitive periods early in development, we conclude with a discussion on the effects of traumatic experience on the developing oxytocin system. Epigenetic modification of genes involved in oxytocin signaling might be involved in the mechanisms mediating the long-term influence of early adverse experiences on socio-behavioral outcomes.

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Test of association between 10 single nucleotide polymorphisms in the oxytocin receptor gene and conduct disorder

Cited by 19 publications

References 34 publications

Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression

Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression

Genetics of aggressive behavior: An overview

Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience

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