The role of genetic variants in genes regulating the oxytocin–vasopressin neurohumoral system in childhood-onset aggression

Malik, Ayesha; Zai, Clement C.; Berall, Laura; Abu, Zihad; Din, F.; Nowrouzi, Behdin; Chen, Sheng; Beitchman, Joseph H.

doi:10.1097/ypg.0000000000000044

Cited by 29 publications

(20 citation statements)

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“…Genomic DNA was extracted from saliva, blood, and buccal cells using procedures outlined by Malik et al (2014). Manufacturer's protocol for TaqMan s SNP Assays (Life Technologies, Applied Biosystems Inc., Foster City, CA, USA) was used to genotype five SNPs in FKBP5, rs4713916, rs9470080, rs1360780, rs9296158, and rs3800373 (see Supplementary materials for detailed positions and procedures).…”

Section: Dna Collection and Genotypingmentioning

confidence: 99%

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression

Bryushkova

Zai

Sheng

et al. 2016

Psychiatry Research

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Section: Dna Collection and Genotypingmentioning

confidence: 99%

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression

Bryushkova

Zai

Sheng

et al. 2016

Psychiatry Research

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“…The genes for vasopressin and for the oxytocin and vasopressin receptors (AVP, OXTR, AVPR1A and AVPR1B) have been associated with aggression in children [Malik et al, 2012[Malik et al, , 2014Zai et al, 2012b;Luppino et al, 2014]. Oxytocin and vasopressin encode neurohypophysial hormones with primary roles in sexual reproduction and in water retention, respectively, but they have also Sakai et al [2006Sakai et al [ , 2007Sakai et al [ , 2010 SLC6A3 (DAT1) Solute carrier family 6 (neurotransmitter transporter), member 3 (dopamine transporter)…”

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

114

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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“…3 Because ADHD is related strongly with aggression, studies that showed the association between aggression and the vasopressin system may also indicate the possible role of vasopressin in ADHD. 30,31 On the other hand, both oxytocin and vasopressin are regarded as social hormones and are closely related neuropeptides; recent studies that reported relations between ADHD and the oxytocinergic system have also suggested the link between the vasopressinergic system and ADHD. 7,8 The present study found no significant difference between the ADHD and control groups for plasma vasopressin levels and could not provide any direct evidence concerning the possible role of vasopressin in ADHD.…”

Section: Discussionmentioning

confidence: 99%

Exploratory study to evaluate plasma vasopressin and apelin‐13 levels in children with attention‐deficit hyperactivity disorder

Bi̇lgi̇ç

Toker

Uysal

2016

Psychiatry Clin Neurosci

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Aim: Vasopressin exerts robust influences on social communication and behavior in humans. Apelin is a relatively novel neuropeptide that could counteract vasopressin's actions and has been shown to be closely related with a broad range of physiological functions. Abnormalities in vasopressin and apelin have been detected in a variety of psychiatric disorders, but their relation to attention-deficit hyperactivity disorder (ADHD) is unknown. In the present study, we explored the plasma levels of vasopressin and apelin-13 in children with ADHD.Methods: Thirty-four children with ADHD and 36 healthy controls were enrolled in this study. The severity of ADHD symptoms was assessed via Conners' Parent Rating Scale and Conners' Teacher Rating Scale. Plasma levels of vasopressin and apelin-13 were measured using commercial enzymelinked immunosorbent assay kits. Results:The mean plasma apelin-13 levels were significantly higher in male children with ADHD than in male control subjects; no significant difference was found between the groups for plasma apelin-13 levels in girls or in the entire subject cohort. Plasma vasopressin levels did not show any significant differences between groups. There were no significant correlations between plasma levels of these neuropeptides and scores for Conners' Parent Rating Scale and Conners' Teacher Rating Scale. Conclusion:Our results suggest a sex-specific association between plasma apelin-13 levels and ADHD. Apelin-13 may play a role in the etiopathogenesis of ADHD either with a direct impact on the apelin receptor or via its opposing effect on the vasopressinergic system. Key words: apelin-13, attention-deficit hyperactivity disorder, children, plasma, vasopressin.A TTENTION-DEFICIT HYPERACTIVITY DISOR-DER (ADHD) is a childhood-onset neurodevelopmental condition characterized by inattention, hyperactivity, and/or impulsivity that can persist into adulthood with deleterious effects on social, academic, and behavioral outcomes.1 The etiology of ADHD involves complex interactions of neuroanatomical and neurochemical systems, but the precise neurobiological mechanisms underlying the disorder are currently unclear. Understanding the etiopathogenesis of ADHD would aid in both its diagnosis and in the development of new treatments for this complex disorder.The vasopressinergic system in the brain participates in the modulation of social behaviors, including social communication, parental care, parent-offspring bonding, pair-bonding, and sexual behavior.2 Because social deficiencies are core symptoms of autism spectrum disorders (ASD), in recent years, a growing number of studies have investigated the potential relation between the vasopressinergic system and ASD. [3][4][5] These studies have yielded conflicting results regarding the alteration of blood vasopressin concentrations

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The role of genetic variants in genes regulating the oxytocin–vasopressin neurohumoral system in childhood-onset aggression

Abstract: Genetic variants regulating the OXT-AVP system may be associated with childhood-onset aggression.

Cited by 29 publications

References 28 publications

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression

Genetics of aggressive behavior: An overview

Exploratory study to evaluate plasma vasopressin and apelin‐13 levels in children with attention‐deficit hyperactivity disorder

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