The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Larry J Young - One of the best experts on this subject based on the ideXlab platform.
-
variation in the Oxytocin Receptor gene predicts brain region specific expression and social attachment
Biological Psychiatry, 2016Co-Authors: Lanikea B. King, Nicholas W. Eyrich, Hasse Walum, Kiyoshi Inoue, Larry J YoungAbstract:Abstract Background Oxytocin (OXT) modulates several aspects of social behavior. Intranasal OXT is a leading candidate for treating social deficits in patients with autism spectrum disorder, and common genetic variants in the human OXTR gene are associated with emotion recognition, relationship quality, and autism spectrum disorder. Animal models have revealed that individual differences in Oxtr expression in the brain drive social behavior variation. Our understanding of how genetic variation contributes to brain OXTR expression is very limited. Methods We investigated Oxtr expression in monogamous prairie voles, which have a well-characterized OXT system. We quantified brain region–specific levels of Oxtr messenger RNA and Oxytocin Receptor protein with established neuroanatomic methods. We used pyrosequencing to investigate allelic imbalance of Oxtr mRNA, a molecular signature of polymorphic genetic regulatory elements. We performed next-generation sequencing to discover variants in and near the Oxtr gene. We investigated social attachment using the partner preference test. Results Our allelic imbalance data demonstrate that genetic variants contribute to individual differences in Oxtr expression, but only in particular brain regions, including the nucleus accumbens, where Oxytocin Receptor signaling facilitates social attachment. Next-generation sequencing identified one polymorphism in the Oxtr intron, near a putative cis -regulatory element, explaining 74% of the variance in striatal Oxtr expression specifically. Males homozygous for the high expressing allele display enhanced social attachment. Conclusions Taken together, these findings provide convincing evidence for robust genetic influence on Oxtr expression and provide novel insights into how noncoding polymorphisms in OXTR might influence individual differences in human social cognition and behavior.
-
common polymorphism in the Oxytocin Receptor gene oxtr is associated with human social recognition skills
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Karen N Conneely, David Skuse, Adriana Lori, Joseph F Cubells, Irene Lee, Kaija Puura, Terho Lehtimaki, Elisabeth B Binder, Larry J YoungAbstract:The neuropeptides Oxytocin and vasopressin are evolutionarily conserved regulators of social perception and behavior. Evidence is building that they are critically involved in the development of social recognition skills within rodent species, primates, and humans. We investigated whether common polymorphisms in the genes encoding the Oxytocin and vasopressin 1a Receptors influence social memory for faces. Our sample comprised 198 families, from the United Kingdom and Finland, in whom a single child had been diagnosed with high-functioning autism. Previous research has shown that impaired social perception, characteristic of autism, extends to the first-degree relatives of autistic individuals, implying heritable risk. Assessments of face recognition memory, discrimination of facial emotions, and direction of gaze detection were standardized for age (7–60 y) and sex. A common SNP in the Oxytocin Receptor (rs237887) was strongly associated with recognition memory in combined probands, parents, and siblings after correction for multiple comparisons. Homozygotes for the ancestral A allele had impairments in the range −0.6 to −1.15 SD scores, irrespective of their diagnostic status. Our findings imply that a critical role for the Oxytocin system in social recognition has been conserved across perceptual boundaries through evolution, from olfaction in rodents to visual memory in humans.
-
evidence that Oxytocin exerts anxiolytic effects via Oxytocin Receptor expressed in serotonergic neurons in mice
The Journal of Neuroscience, 2009Co-Authors: Masahide Yoshida, Larry J Young, Yuki Takayanagi, Kiyoshi Inoue, Tadashi Kimura, Tatsushi Onaka, Katsuhiko NishimoriAbstract:The Oxytocin Receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which Oxytocin Receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize Oxytocin Receptor-expressing neurons within the brain, we generated an Oxytocin Receptor-reporter mouse in which part of the Oxytocin Receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for Oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT 2A/2C Receptor antagonist blocked the anxiolytic effect of Oxytocin, suggesting that Oxytocin Receptor activation in serotonergic neurons mediates the anxiolytic effects of Oxytocin. This is the first demonstration that Oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of Oxytocin Receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the Oxytocin and serotonin systems have been implicated.
-
variation in Oxytocin Receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles
The Journal of Neuroscience, 2009Co-Authors: Heather E Ross, Sara M Freeman, Lauren L Spiegel, Xianghui Ren, Ernest Terwilliger, Larry J YoungAbstract:Oxytocin Receptors in the nucleus accumbens have been implicated in the regulation of alloparental behavior and pair bond formation in the socially monogamous prairie vole. Oxytocin Receptor density in the nucleus accumbens is positively correlated with alloparenting in juvenile and adult female prairie voles, and Oxytocin Receptor antagonist infused into the nucleus accumbens blocks this behavior. Furthermore, prairie voles have higher densities of Oxytocin Receptors in the accumbens than nonmonogamous rodent species, and blocking accumbal Oxytocin Receptors prevents mating-induced partner preference formation. Here we used adeno-associated viral vector gene transfer to examine the functional relationship between accumbal Oxytocin Receptor density and social behavior in prairie and meadow voles. Adult female prairie voles that overexpress Oxytocin Receptor in the nucleus accumbens displayed accelerated partner preference formation after cohabitation with a male, but did not display enhanced alloparental behavior. However, partner preference was not facilitated in nonmonogamous meadow voles by introducing Oxytocin Receptor into the nucleus accumbens. These data confirm a role for Oxytocin Receptor in the accumbens in the regulation of partner preferences in female prairie voles, and suggest that Oxytocin Receptor expression in the accumbens is not sufficient to promote partner preferences in nonmonogamous species. These data are the first to demonstrate a direct relationship between Oxytocin Receptor density in the nucleus accumbens and variation in social attachment behaviors. Thus, individual variation in Oxytocin Receptor expression in the striatum may contribute to natural diversity in social behaviors.
-
pervasive social deficits but normal parturition in Oxytocin Receptor deficient mice
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Yuki Takayanagi, Masahide Yoshida, Tadashi Kimura, Tatsushi Onaka, Heather E Ross, Isadora F Bielsky, Masaki Kawamata, Teruyuki Yanagisawa, Martin M Matzuk, Larry J YoungAbstract:The Oxytocin Receptor (OXTR) and its ligand, Oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr-/-) and compared them with OXT-deficient (Oxt-/-) mice. Oxtr-/- mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr-/- dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr-/- males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr-/- males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt-/- males from Oxt-/- dams, but not from Oxt+/- dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.
David Skuse - One of the best experts on this subject based on the ideXlab platform.
-
common polymorphism in the Oxytocin Receptor gene oxtr is associated with human social recognition skills
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Karen N Conneely, David Skuse, Adriana Lori, Joseph F Cubells, Irene Lee, Kaija Puura, Terho Lehtimaki, Elisabeth B Binder, Larry J YoungAbstract:The neuropeptides Oxytocin and vasopressin are evolutionarily conserved regulators of social perception and behavior. Evidence is building that they are critically involved in the development of social recognition skills within rodent species, primates, and humans. We investigated whether common polymorphisms in the genes encoding the Oxytocin and vasopressin 1a Receptors influence social memory for faces. Our sample comprised 198 families, from the United Kingdom and Finland, in whom a single child had been diagnosed with high-functioning autism. Previous research has shown that impaired social perception, characteristic of autism, extends to the first-degree relatives of autistic individuals, implying heritable risk. Assessments of face recognition memory, discrimination of facial emotions, and direction of gaze detection were standardized for age (7–60 y) and sex. A common SNP in the Oxytocin Receptor (rs237887) was strongly associated with recognition memory in combined probands, parents, and siblings after correction for multiple comparisons. Homozygotes for the ancestral A allele had impairments in the range −0.6 to −1.15 SD scores, irrespective of their diagnostic status. Our findings imply that a critical role for the Oxytocin system in social recognition has been conserved across perceptual boundaries through evolution, from olfaction in rodents to visual memory in humans.
Florina Uzefovsky - One of the best experts on this subject based on the ideXlab platform.
-
the Oxytocin Receptor gene predicts brain activity during an emotion recognition task in autism
Molecular Autism, 2019Co-Authors: Varun Warrier, Florina Uzefovsky, Richard A I Bethlehem, Simone G Shamaytsoory, Amber N V Ruigrok, Rosemary Holt, Michael D Spencer, Lindsay R Chura, Bhismadev ChakrabartiAbstract:Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the Oxytocin Receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Participants were adolescents (mean age = 14.7 ± 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the ‘Reading the Mind in the Eyes’ Test (Eyes Test). Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism.
-
Oxytocin Receptor and vasopressin Receptor 1a genes are respectively associated with emotional and cognitive empathy
Hormones and Behavior, 2015Co-Authors: Salomon Israel, Idan Shalev, Florina Uzefovsky, Shany Edelman, Yael Raz, David Mankuta, Ariel Knafonoam, Richard P EbsteinAbstract:Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the Oxytocin Receptor (OXTR) and the arginine vasopressin Receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both Oxytocin and vasopressin in modulating human emotions.
-
the Oxytocin Receptor oxtr contributes to prosocial fund allocations in the dictator game and the social value orientations task
PLOS ONE, 2009Co-Authors: Salomon Israel, Elad Lerer, Idan Shalev, Florina Uzefovsky, Mathias Riebold, Efrat Laiba, Rachel Bachnermelman, Anat Maril, Gary Bornstein, Ariel KnafoAbstract:Background Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a Receptor gene (AVPR1a). In the current investigation, the gene encoding the related Oxytocin Receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (p<0.05). A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher's exact test). Conclusions The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decision making converges with a large body of animal research showing that Oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the Oxytocin Receptor gene, an important element of mammalian social circuitry, underlie such individual differences.
Joseph D Dougherty - One of the best experts on this subject based on the ideXlab platform.
-
Oxytocin Receptor activation does not mediate associative fear deficits in a williams syndrome model
Genes Brain and Behavior, 2021Co-Authors: Kayla R Nygaard, Georgianna G. Gould, Raylynn G Swift, Rebecca M Glick, Rachael E Wagner, Susan E Maloney, Joseph D DoughertyAbstract:Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias, and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, Oxytocin dysregulation is hypothesized to be involved as some studies have shown elevated blood Oxytocin and altered Oxytocin Receptor expression in patients. A 'Complete Deletion' mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These Complete Deletion mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether Oxytocin dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an Oxytocin Receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in Complete Deletion mice. Thus, increased Oxytocin signaling is not acutely responsible for this phenotype. We also evaluated Oxytocin Receptor and serotonin transporter availability in regions related to fear learning, memory, and sociability using autoradiography in wild type and Complete Deletion mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in Oxytocin Receptor expression in the lateral septal nucleus, and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the Oxytocinergic system caused by deletion of the Williams locus.
-
Oxytocin Receptor activation does not mediate associative fear deficits in a williams syndrome model
bioRxiv, 2021Co-Authors: Kayla R Nygaard, Georgianna G. Gould, Raylynn G Swift, Rebecca M Glick, Rachael E Wagner, Susan E Maloney, Joseph D DoughertyAbstract:Williams Syndrome is caused by a deletion of 26-28 genes on chromosome 7q11.23. Patients with this disorder have distinct behavioral phenotypes including learning deficits, anxiety, increased phobias, and hypersociability. Some studies also suggest elevated blood Oxytocin and altered Oxytocin Receptor expression, and this Oxytocin dysregulation is hypothesized to be involved in the underlying mechanisms driving a subset of these phenotypes. A 9Complete Deletion9 mouse, modeling the hemizygous critical region deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These Complete Deletion mice also exhibited impaired fear responses in the conditioned fear task. Here, we address whether Oxytocin dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an Oxytocin Receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in Complete Deletion mice. Thus, increased Oxytocin signaling is not acutely responsible for this phenotype. We also evaluated Oxytocin Receptor and serotonin transporter availability in regions related to fear learning, memory, and sociability using autoradiography in wild type and Complete Deletion mice. While we identified trends in lowered Oxytocin Receptor expression in the lateral septal nucleus, and trends towards lowered serotonin transporter availability in the striatum and orbitofrontal cortex, we found no significant differences after correction. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the Oxytocinergic system caused by deletion of the Williams locus.
Bhismadev Chakrabarti - One of the best experts on this subject based on the ideXlab platform.
-
the Oxytocin Receptor gene predicts brain activity during an emotion recognition task in autism
Molecular Autism, 2019Co-Authors: Varun Warrier, Florina Uzefovsky, Richard A I Bethlehem, Simone G Shamaytsoory, Amber N V Ruigrok, Rosemary Holt, Michael D Spencer, Lindsay R Chura, Bhismadev ChakrabartiAbstract:Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the Oxytocin Receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Participants were adolescents (mean age = 14.7 ± 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the ‘Reading the Mind in the Eyes’ Test (Eyes Test). Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism.
-
genetic variation in the Oxytocin Receptor oxtr gene is associated with asperger syndrome
Molecular Autism, 2014Co-Authors: Agnese Di Napoli, Varun Warrier, Simon Baroncohen, Bhismadev ChakrabartiAbstract:Background: Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for Oxytocin (OXT) and Oxytocin Receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the Oxytocin/Oxytocin Receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods: The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results: There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs22684 90-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions: This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.
