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Larry J Young - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Neurobiology of Social Bonding: Implications for Autism Spectrum Disorders
    2020
    Co-Authors: Larry J Young
    Abstract:

    Social relationships are at the core of every healthy society and the quality of early Social Attachments contributes to emotional and Social development. I will discuss the neurobiological mechanisms underlying Social Attachment and bonding. The highly Social and monogamous prairie vole is an ideal animal model for investigating the biological mechanisms of Social Attachment and bonding. Studies in voles have revealed that the neuropeptides oxytocin and vasopressin promote Social bonding. Furthermore, variation in the oxytocin and vasopressin systems contributes to diversity in Social behavior both across species and within populations. I will discuss the genetic mechanisms giving rise to diversity in Social organization in voles as well as individual variation in Social behavior. Finally I will discuss parallels between these studies in voles and recent studies in humans which suggest that these mechanisms are highly conserved from rodent to man. In humans, oxytocin enhances trust and empathy, increases gaze to the eyes, and Socially reinforced learning. Polymorphisms in the human vasopressin receptor gene have been associated with measures of pair bonding. These findings have important implications for developing novel therapeutic approaches to enhance Social cognition in psychiatric disorders such as autism spectrum disorders.

  • The Biochemistry of Family Commitment and Youth Competence: Lessons from Animal Models
    The Search Institute Series on Developmentally Attentive Community and Society, 2020
    Co-Authors: Larry J Young, Darlene D. Francis
    Abstract:

    Recent advances in neuroscience are beginning to provide fresh insights into the mechanisms for Social interaction, including the molecular and cellular processes involved in the formation of Social bonds. Understanding the biochemical factors that contribute to Social Attachment, as well as the biological consequences of parent–offspring interactions, may contribute to better understanding of normative development. In this chapter, we will review some of the results from studies of nonhuman animals revealing the neurobiological causes and consequences of Social bonding and parental care. First, we describe a monogamous rodent that has provided an extensive understanding of the molecular and cellular basis of selective Social Attachment between mates. This research may serve as a model for understanding Social bonding in general as the same mechanisms may contribute to many aspects of Social Attachments. We will then provide an overview of the underlying neurobiology of parental care. Finally, we will describe studies that examine the enduring consequences of differing parental styles on behavior and neurochemistry and provide a model of how these behaviors may be perpetuated across generations. We must stress that the reader bear in mind that most of the data presented here are from rodent studies, and there is very little evidence at this time that these same underlying mechanisms are similar in humans. However, understanding these processes in animals provides a perspective for thinking about how biological and environmental processes may govern behavioral outcomes in human beings.

  • Oxytocin and vasopressin neural networks: Implications for Social behavioral diversity and translational neuroscience
    Neuroscience & Biobehavioral Reviews, 2017
    Co-Authors: Z. Johnson, Larry J Young
    Abstract:

    Abstract Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate Social learning and behavior, including conspecific recognition, Social Attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in Social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in Social recognition, Social Attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of Social behavioral diversity, with a particular focus on neural networks that modulate Social learning, behavior, and salience of sociosensory stimuli during species-typical Social contexts.

  • The Neurobiology and Genetics of Affiliation and Social Bonding in Animal Models
    Animal Models of Behavior Genetics, 2016
    Co-Authors: Zoe R. Donaldson, Larry J Young
    Abstract:

    Affiliation and Social Attachments in some form are critical for the survival of all mammalian species and significantly influence human mental health. Although very little is known regarding the underlying neurobiological mechanisms influencing the development of human relationships, studies using animal models have gained insights into the regulation of this process in other species. In this chapter we will discuss several animal models that have been particularly useful for investigating the neural and genetic mechanisms modulating affiliation and Social Attachment. We focus on a core set of signaling systems that modulate perception of Social cues, Social memory, motivation, and reward. The contribution of genetics will be reviewed where information is available. Specifically, we outline the role that oxytocin and vasopressin systems play in modulating Social recognition memory, as well as the interactions of dopamine and endogenous opioids on Social motivation and reward. The parallel actions of these neuromodulators represent a highly conserved, Socially directed motivational system underlying multiple forms of Social Attachment, including mother–infant interactions and adult pair bonds. A better understanding of these systems has the potential to provide insights into complex human Social relationships. It may also pave the way for novel therapeutics to treat the sociobehavioral deficits associated with autism and other disorders.

  • variation in the oxytocin receptor gene predicts brain region specific expression and Social Attachment
    Biological Psychiatry, 2016
    Co-Authors: Lanikea B. King, Nicholas W. Eyrich, Hasse Walum, Kiyoshi Inoue, Larry J Young
    Abstract:

    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.

Thomas R Insel - One of the best experts on this subject based on the ideXlab platform.

  • is Social Attachment an addictive disorder
    Physiology & Behavior, 2003
    Co-Authors: Thomas R Insel
    Abstract:

    There is a considerable literature on the neurobiology of reward, based largely on studies of addiction or substance abuse. This review considers the possibility that the neural circuits that mediate reward evolved for ethologically relevant cues, such as Social Attachment. Specifically, mesocorticolimbic dopamine appears important for maternal behavior in rats and pair bonding in monogamous voles. It is not yet clear that dopamine in this pathway mediates the hedonic properties of Social bond formation or whether dopamine's role is more relevant to developing associative networks or assigning salience to Social stimuli. The neuropeptides oxytocin (OT) and vasopressin (AVP) appear to be critical for linking Social signals to the mesocorticolimbic circuit.

  • cellular mechanisms of Social Attachment
    Hormones and Behavior, 2001
    Co-Authors: Larry J Young, Brenden Gingrich, Thomas R Insel
    Abstract:

    Pharmacological studies in prairie voles have suggested that the neuropeptides oxytocin and vasopressin play important roles in behaviors associated with monogamy, including affiliation, paternal care, and pair bonding. Our laboratory has investigated the cellular and neuroendocrine mechanisms by which these peptides influence affiliative behavior and Social Attachment in prairie voles. Monogamous prairie voles have a higher density of oxytocin receptors in the nucleus accumbens than do nonmonogamous vole species; blockade of these receptors by site-specific injection of antagonist in the female prairie vole prevents partner preference formation. Prairie voles also have a higher density of vasopressin receptors in the ventral pallidal area, which is the major output of the nucleus accumbens, than montane voles. Both the nucleus accumbens and ventral pallidum are key relay nuclei in the brain circuits implicated in reward, such as the mesolimbic dopamine and opioid systems. Therefore, we hypothesize that oxytocin and vasopressin may be facilitating affiliation and Social Attachment in monogamous species by modulating these reward pathways.

  • dopamine d2 receptors in the nucleus accumbens are important for Social Attachment in female prairie voles microtus ochrogaster
    Behavioral Neuroscience, 2000
    Co-Authors: Brenden Gingrich, Zuoxin Wang, Carissa J Cascio, Thomas R Insel
    Abstract:

    The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of Social Attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of Social Attachments in female voles.

  • a neurobiological basis of Social Attachment
    American Journal of Psychiatry, 1997
    Co-Authors: Thomas R Insel
    Abstract:

    Objective: Although an inability to form normal Social Attachments characterizes many forms of psychopathology, there has been little study of the neural basis of Social bond formation. The primary purpose of this article is to describe a novel approach to the neurobiology of Attachment. Method: The author reviews animal research on two closely related neuropeptides, oxytocin and vasopressin, implicated in the central mediation of Attachment behaviors. These neuropeptides appear to be important for the initiation of pair bonds and parental behaviors as well as the infant’s response to Social separation. Results: Both cellular and molecular studies have begun to reveal the mechanisms by which oxytocin and vasopressin neural pathways are regulated, leading to a preliminary understanding of how these hormones act within the brain to influence complex Social behaviors. Conclusions: Although their function in the human brain has yet to be demonstrated, the available evidence suggests that oxytocin and vasopressin may prove to be important in the pathophysiology of clinical disorders, such as autism, characterized by an inability to form normal Social Attachments. (Am J Psychiatry 1997; 154:726‐735)

Zuoxin Wang - One of the best experts on this subject based on the ideXlab platform.

  • Neurobiology of Mental Illness - The Neurobiology of Social Attachment
    Neurobiology of Mental Illness, 2020
    Co-Authors: Dennis S. Charney, Adam S. Smith, Zuoxin Wang
    Abstract:

    Social Attachment is an intrinsic component of human life. As Aristotle famously noted, “man is by nature a Social animal”, and as such, Social Attachments are wellsprings for our survival, success, and mental health. This dynamic process – involving complex behaviors, multimodal sensory information, and cognitive processes – leads infants to bond to their caregivers or two people to fall in love. Now, the neurobiological basis of Attachment is coming to light, illuminating the role of various monoamines and neuropeptides. It is the goal of this chapter to describe the current knowledge of the neurobiology behind Social Attachments by uncoupling the neurochemical and neuroanatomy of individual bond-related behaviors, reconstructing uniformed neural systems, and correlating these findings to our understanding of human analogs.

  • The Neurochemistry of Pair Bonding
    Current Directions in Psychological Science, 2020
    Co-Authors: J. Thomas Curtis, Zuoxin Wang
    Abstract:

    The formation and maintenance of Social Attachments are fundamental to human biology. Because deficits in the ability to form such Attachments are associated with a variety of psychological disorders, an understanding of the neural basis of Social Attachment may provide insights into the causes of such disorders. Comparative studies using several closely related species of voles that display different Social organizations and behaviors have begun to provide important insights into the neurochemical events underlying Social Attachment. Here we review recent developments in the study of Social Attachment, focusing on the roles of specific neurochemical systems in pair-bond formation.

  • Comprehensive Physiology - Neuropeptide Regulation of Social Attachment: The Prairie Vole Model.
    Comprehensive Physiology, 2016
    Co-Authors: Manal Tabbaa, Brennan Paedae, Zuoxin Wang
    Abstract:

    : Social Attachments are ubiquitous among humans and integral to human health. Although great efforts have been made to elucidate the neural underpinnings regulating Social Attachments, we still know relatively little about the neuronal and neurochemical regulation of Social Attachments. As a laboratory animal research model, the Socially monogamous prairie vole (Microtus ochrogaster) displays behaviors paralleling human Social Attachments and thus has provided unique insights into the neural regulation of Social behaviors. Research in prairie voles has particularly highlighted the significance of neuropeptidergic regulation of Social behaviors, especially of the roles of oxytocin (OT) and vasopressin (AVP). This article aims to review these findings. We begin by discussing the role of the OT and AVP systems in regulating Social behaviors relevant to Social Attachments, and thereafter restrict our discussion to studies in prairie voles. Specifically, we discuss the role of OT and AVP in adult mate Attachments, biparental care, Social isolation, and Social buffering as informed by studies utilizing the prairie vole model. Not only do these studies offer insight into Social Attachments in humans, but they also point to dysregulated mechanisms in several mental disorders. We conclude by discussing these implications for human health. © 2017 American Physiological Society. Compr Physiol 7:81-104, 2017.

  • the neurobiology of Social Attachment a comparative approach to behavioral neuroanatomical and neurochemical studies
    Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2008
    Co-Authors: Kimberly A Young, Zuoxin Wang
    Abstract:

    The formation and maintenance of Social bonds in adulthood is an essential component of human health. However studies investigating the underlying neurobiology of such behaviors have been scarce. Microtine rodents offer a unique comparative animal model to explore the neural processes responsible for pair bonding and its associated behaviors. Studies using monogamous prairie voles and other related species have recently offered insight into the neuroanatomical, neurobiological, and neurochemical underpinnings of Social Attachment. In this review, we will discuss the utility of the microtine rodents in comparative studies by exploring their natural history and Social behavior in the laboratory. We will then summarize the data implicating vasopressin, oxytocin, and dopamine in the regulation of pair bonding. Finally, we will discuss the ways in which these neurochemical systems may interact to mediate this complex behavior.

  • Dopamine, oxytocin, and vasopressin receptor binding in the medial prefrontal cortex of monogamous and promiscuous voles
    Neuroscience Letters, 2005
    Co-Authors: Michael D. Smeltzer, Brandon J Aragona, J. Thomas Curtis, Zuoxin Wang
    Abstract:

    Comparisons between monogamous and promiscuous vole species have proven useful in examining neurobiological mechanisms underlying Social Attachment. Reward processing is important for Social Attachment, and the medial prefrontal cortex (mPFC) exerts a direct influence on reward pathways. Dopamine (DA), oxytocin (OT), and arginine vasopressin (AVP) all have been implicated in the regulation of Social Attachment in monogamous voles. Therefore, we used radiolabeled ligands to examine dopamine D1- and D2-like, OT, and AVP V1a receptor binding densities in the mPFC of monogamous and promiscuous voles. Species differences were found; monogamous voles had higher densities of D2-like and OT receptor binding and lower densities of D1-like and V1a receptor binding than did promiscuous voles. Sex differences also were found; females had higher densities of OT receptor binding but lower densities of V1a receptor binding than did males in both species. Further, the laminar distribution of receptor binding indicates the possibility of an interaction between DA and OT systems in the mPFC in the regulation of Social Attachment. Differences in D1- and D2-like receptor binding between species are discussed in terms of how they might modulate cortical activity and subsequent DA release in the nucleus accumbens (NAcc). © 2005 Elsevier Ireland Ltd. All rights reserved.

Carole Adam - One of the best experts on this subject based on the ideXlab platform.

  • Review of Agent Based Modelling of Social Attachment in Crisis Situations
    International Journal of Information Systems for Crisis Response Management, 2020
    Co-Authors: Julius Bañgate, Julie Dugdale, Elise Beck, Carole Adam
    Abstract:

    Human behaviour during crisis evacuations is Social in nature. In particular, Social Attachment theory posits that proximity of familiar people, places, objects, etc., promotes calm and a feeling of safety, while their absence triggers panic or flight. In closely bonded groups such as families, members seek each other and evacuate as one. This makes Attachment bonds necessary in the development of realistic models of mobility during crises. This article presents a review of evacuation behaviour, theories on Social Attachment, crisis mobility, and agent-based models. It was found that Social Attachment influences mobility in the different stages of evacuation (pre, during and post). Based on these findings, a multi-agent model of mobility during seismic crises (SOLACE) is being developed, and it is implemented using the belief, desire and intention (BDI) agent architecture.

  • A multi-agent system approach in evaluating human spatio-temporal vulnerability to seismic risk using Social Attachment
    arXiv: Multiagent Systems, 2019
    Co-Authors: Julius Bañgate, Julie Dugdale, Elise Beck, Carole Adam
    Abstract:

    Social Attachment theory states that individuals seek the proximity of Attachment figures (e.g. family members, friends, colleagues, familiar places or objects) when faced with threat. During disasters, this means that family members may seek each other before evacuating, gather personal property before heading to familiar exits and places, or follow groups/crowds, etc. This hard-wired human tendency should be considered in the assessment of risk and the creation of disaster management plans. Doing so may result in more realistic evacuation procedures and may minimise the number of casualties and injuries. In this context, a dynamic spatio-temporal analysis of seismic risk is presented using SOLACE, a multi-agent model of pedestrian behaviour based on Social Attachment theory implemented using the Belief-Desire-Intention approach. The model focuses on the influence of human, Social, physical and temporal factors on successful evacuation. Human factors considered include perception and mobility defined by age. Social factors are defined by Attachment bonds, Social groups, population distribution, and cultural norms. Physical factors refer to the location of the epicentre of the earthquake, spatial distribution/layout and attributes of environmental objects such as buildings, roads, barriers (cars), placement of safe areas, evacuation routes, and the resulting debris/damage from the earthquake. Experiments tested the influence of time of the day, presence of disabled persons and earthquake intensity. Initial results show that factors that influence arrivals in safe areas include (a) human factors (age, disability, speed), (b) pre-evacuation behaviours, (c) perception distance (Social Attachment, time of day), (d) Social interaction during evacuation, and (e) physical and spatial aspects, such as limitations imposed by debris (damage), and the distance to safe areas. To validate the results, scenarios will be designed with stakeholders, who will also take part in the definition of a serious game. The recommendation of this research is that both Social and physical aspects should be considered when defining vulnerability in the analysis of risk.

  • A MULTI-AGENT SYSTEM APPROACH IN EVALUATING HUMAN SPATIO-TEMPORAL VULNERABILITY TO SEISMIC RISK USING Social Attachment
    WIT transactions on engineering sciences, 2018
    Co-Authors: Julius Bañgate, Julie Dugdale, Elise Beck, Carole Adam
    Abstract:

    The theory of Social Attachment states that individuals seek the proximity of Attachment figures (e.g. family members, friends, colleagues, familiar places or objects) when faced with threat. During disasters, this means that family members may seek each other before evacuating, gather personal property before heading to familiar exits and places, or follow groups/crowds, etc. This hard-wired human tendency should be considered in the assessment of risk and the formulation of disaster management plans. Doing so may result in more realistic evacuation procedures and may minimise the number of casualties and injuries. In this context, a dynamic spatio-temporal analysis of seismic risk is presented here using SOLACE, a multi-agent model of pedestrian behaviour based on the theory of Social Attachment applied using the Belief-Desire-Intention approach. The model focuses on the influence of human, Social, physical and temporal factors on successful evacuation. Human factors considered include perception and mobility defined by age. Social factors are defined by Attachment bonds, Social groups, population distribution, and cultural norms. Physical factors refer to the location of the epicentre of the earthquake, the spatial distribution/layout and attributes of environmental objects such as buildings, roads, barriers (cars), placement of safe areas, evacuation routes, and the resulting debris/damage from the earthquake. Experiments tested the influence of time of the day, the presence of disabled persons and earthquake intensity. Initial results show that factors that influence arrivals in safe areas include (a) human factors (age, disability, speed), (b) pre-evacuation behaviours, (c) perception distance (Social Attachment, time of day), (d) Social interaction during evacuation, and (e) physical and spatial aspects, such as limitations imposed by debris (damage), and the distance to safe areas. To validate the results, scenarios have to be designed with stakeholders, who would also take part in the definition of a serious game. The recommendation of this research is that both Social and physical aspects must be considered when defining vulnerability in risk analysis.

  • ICT-DM - SOLACE a multi-agent model of human behaviour driven by Social Attachment during seismic crisis
    2017 4th International Conference on Information and Communication Technologies for Disaster Management (ICT-DM), 2017
    Co-Authors: Julius Bañgate, Julie Dugdale, Elise Beck, Carole Adam
    Abstract:

    Human behaviour during crisis is Social in nature. Affiliation, activated by threat, results in individuals seeking the proximity of Attachment figures (i.e. family members, friends, colleagues, strangers, Social groups, familiar places, and objects). This affects the actions, directions, and speeds adopted by individuals seeking safe areas. This paper presents SOLACE, a multi-agent model of human behaviour during seismic crisis based on Social Attachment theory. SOLACE is an attempt to show the effect of Social Attachment on the number of victims, and the time that it takes, to reach a safe area; this increases the realism in evacuation modelling. Real-geographic data are used to define the spatial context of the crisis environment, delimit mobility with barriers (e.g. buildings, debris), and constrain movement to freespace. A belief, desire, and intention (BDI) approach was adopted to integrate Social bonds in human agent interaction and mobility. Initial results include realism in: (1) the synthetic crisis environment indicated by a power law distribution of earthquake effects: (a) intensities on buildings and shaking felt by human agents, and (b) evacuation delay, (2) agent movement and interaction (e.g. parent with child) influencing speed of evacuation.

  • SOLACE a multi-agent model of human behaviour driven by Social Attachment during seismic crisis
    2017 4th International Conference on Information and Communication Technologies for Disaster Management (ICT-DM), 2017
    Co-Authors: Julius Bañgate, Julie Dugdale, Elise Beck, Carole Adam
    Abstract:

    Human behaviour during crisis is Social in nature. Affiliation, activated by threat, results in individuals seeking the proximity of Attachment figures (i.e. family members, friends, colleagues, strangers, Social groups, familiar places, and objects). This affects the actions, directions, and speeds adopted by individuals seeking safe areas. This paper presents SOLACE, a multi-agent model of human behaviour during seismic crisis based on Social Attachment theory. SOLACE is an attempt to show the effect of Social Attachment on the number of victims, and the time that it takes, to reach a safe area; this increases the realism in evacuation modelling. Real-geographic data are used to define the spatial context of the crisis environment, delimit mobility with barriers (e.g. buildings, debris), and constrain movement to freespace. A belief, desire, and intention (BDI) approach was adopted to integrate Social bonds in human agent interaction and mobility. Initial results include realism in: (1) the synthetic crisis environment indicated by a power law distribution of earthquake effects: (a) intensities on buildings and shaking felt by human agents, and (b) evacuation delay, (2) agent movement and interaction (e.g. parent with child) influencing speed of evacuation.

Kiyoshi Inoue - 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, 2016
    Co-Authors: Lanikea B. King, Nicholas W. Eyrich, Hasse Walum, Kiyoshi Inoue, Larry J Young
    Abstract:

    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.

  • Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment
    Biological Psychiatry, 2016
    Co-Authors: Lanikea B. King, Nicholas W. Eyrich, Hasse Walum, Kiyoshi Inoue, Larry J Young
    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.

  • activation of μ opioid receptors in the dorsal striatum is necessary for adult Social Attachment in monogamous prairie voles
    Neuropsychopharmacology, 2011
    Co-Authors: James P. Burkett, Kiyoshi Inoue, Lauren L Spiegel, Anne Z Murphy, Larry J Young
    Abstract:

    Despite significant evidence that opioids are involved in Attachment by mediating Social reward and motivation, the role of opioids in the formation of adult Social Attachments has not been explored. We used the Socially monogamous prairie vole (Microtus ochrogaster) to explore the role of endogenous opioids in Social bonding by examining partner preference formation in female prairie voles. We hypothesized that μ-opioid receptors (MORs) in the striatum have a critical role in partner preference formation. We therefore predicted that peripheral administration of an opioid receptor antagonist would inhibit partner preference formation, and more specifically, that μ-opioid selective receptor blockade within the striatum would inhibit partner preference formation. To test our hypotheses, we first administered the non-selective opioid antagonist naltrexone peripherally to females during an 18-h cohabitation with a male and later tested the female with a partner preference test (PPT). Females showed a dose schedule-dependent decrease in partner preference in the PPT, with females in the continuous dose group displaying stranger preferences. Next, we administered microinjections of the MOR selective antagonist -Phe-Cys-Tyr--Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) into either the nucleus accumbens shell (NAS) or the caudate-putamen (CP) immediately before a 24-h cohabitation with a male, and later tested the female with a PPT. Females receiving CTAP into the CP, but not the NAS, showed no preference in the PPT, indicating an inhibition of partner preference formation. We show here for the first time that MORs modulate partner preference formation in female prairie voles by acting in the CP.