Possible genetic association between vasopressin receptor 1B and child aggression

Zai, Clement C.; Muir, Katherine; Nowrouzi, Behdin; Shaikh, Sajid; Choi, Esther; Berall, Laura; Trépanier, Marc-Olivier; Beitchman, Joseph H.; Kennedy, James L.

doi:10.1016/j.psychres.2012.07.031

Cited by 34 publications

(32 citation statements)

References 39 publications

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“…As mentioned earlier, Avpr1b −/− mice show decreased aggression and altered dominance behavior (Caldwell et al, 2010; Pagani et al, 2015). Human studies including our results have linked AVPR1B to disorders with social components including bipolar type I, depression, autistic traits as measured by EQ, childhood aggression, COMD, suicidal attempts, prosociality, and emotional empathy (Dempster et al, 2007; Chakrabarti et al, 2009; Leszczynska-Rodziewicz et al, 2012; Zai et al, 2012; Szczepankiewicz et al, 2013; Luppino et al, 2014; Wu et al, 2015). Specifically, Zai et al (2012) found rs3536969C to be underrepresented in 177 aggressive child cases as compared to adult matched controls.…”

Section: Discussionmentioning

confidence: 68%

“…Additionally, Caldwell et al (2010) observed increased aggression in Avpr1b −/− mice under specific social conditions including competition, food deprivation, and social experience. In humans, SNPs in AVPR1B have been linked to child aggression, childhood-onset mood disorders (COMD), prosociality, and autistic traits (Dempster et al, 2007, 2009; Chakrabarti et al, 2009; Zai et al, 2012; Wu et al, 2015). In 2015, Wu et al observed a significant association between prosociality (mediated through emotional empathy) and AVPR1B in a non-clinical Han Chinese male sample.…”

Section: Introductionmentioning

confidence: 99%

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ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

et al. 2016

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Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 (p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p = 0.013) and Insistence on Sameness (p = 0.039). Further analyses demonstrated that the haplotype, rs2254298–rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction for multiple comparisons was performed for SNPs tested in each gene region, only AVPR1B SNPs remained significantly associated with ASD diagnosis.Conclusions: Autism is a heterogeneous disorder with many genes and pathways that contribute to its development. SNPs and microsatellites in the receptor genes of OT and AVP are associated with ASD diagnosis and measures of social behavior as well as restricted repetitive behaviors. We reported a novel association with ASD and AVPR1B SNPs. Understanding of genotype-phenotype relationships may be helpful in the development of pharmacological interventions for the OT/AVP system.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

et al. 2016

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“…These findings support the idea that social recognition, as mediated by the Avpr1b in he CA2, is a cognitive ability critical for the expression of appropriate social aggression. Interestingly, in humans, polymorphisms of the Avpr1b are associated with childhood aggression 68 , autistic traits 69 , and a protective effect against recurrent major depression 70 . Also, CA2 non-pyramidal neurons in schizophrenics seem to be preferentially lost 19 and pyramidal neurons in CA2 of schizophrenics are smaller 20 .…”

Section: Discussionmentioning

confidence: 99%

Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2

et al. 2014

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The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator.

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“…OXTR and V1aR are abundant in the developing and adult brain and are typically assumed to be the main brain receptors in the adult, with V1bR expression limited to the pituitary and V2R receptor in the kidney. The presence of V1bR (Hernando et al, 2001) and V2R (Kato et al, 1995;Vargas et al, 2009) in the brain during development has not been ruled out, and this could be an important research avenue for V1bR in particular (Wersinger et al, 2002(Wersinger et al, , 2004Caldwell et al, 2008;Stevenson and Caldwell, 2012;Zai et al, 2012). OXTR and V1aR mRNA and ligand-binding capacity have both been detected prenatally in rats, but their interesting transient developmental patterns appear postnatally, with an adult-like pattern around the time of typical weaning, and further maturing in quantity into adulthood (Lukas et al, 2010) Some, but not all adult sex differences in OXTR expression are influenced by developmental exposure to testosterone (Tribollet et al, 1990;Uhl-Bronner et al, 2005;Dumais et al, 2013) and are actively regulated in adulthood (Bale and Dorsa, 1995a, b;Bale et al, 1995a, b).…”

Section: Dynamic Developmental Profiles: When and Where Are The Factomentioning

confidence: 99%

Developmental Perspectives on Oxytocin and Vasopressin

Hammock

2014

Neuropsychopharmacol

151

146

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The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life.

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Possible genetic association between vasopressin receptor 1B and child aggression

Cited by 34 publications

References 39 publications

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2

Developmental Perspectives on Oxytocin and Vasopressin

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