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Cited by 40Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

A precision medicine approach to oxytocin trials

Open access
Andari, Elissar, Hurlemann, Rene, Young, Larry J.·2017·Current Topics in Behavioral Neurosciences
DOI 10.1007/7854_2017_29PMC PMC5815942
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Abstract

In this chapter, we introduce a new area of social pharmacology that encompasses the study of the role of neuromodulators in modulating a wide range of social behaviors and brain function, with the interplay of genetic and epigenetic factors. There are increasing evidences for the role of the neuropeptide oxytocin in modulating a wide range of social behaviors, in reducing anxiety, and in impacting the social brain network. Oxytocin also promotes social functions in patients with neuropsychiatric disorders, such as autism and reduces anxiety and fear in anxiety disorders. In this chapter, we will emphasize the importance of integrating basic research and clinical human research in determining optimal strategies for drug discoveries for social dysfunctions and anxiety disorders. We will highlight the significance of adopting a precision medicine approach to optimize targeted treatments with oxytocin in neuropsychiatry. Oxytocin effects on social behavior and brain function can vary from one individual to another based on external factors, such as heterogeneity in autism phenotype, childhood experiences, personality, attachment style, and oxytocin receptor polymorphisms. Hence, targeted therapies for subgroups of patients can help alleviating some of the core symptoms and lead to a better future for these patients and their families.

AI snapshot

Written from the paper’s full text.

TL;DR

This chapter argues that oxytocin’s effects on social behavior and brain function are context- and individual-dependent, so oxytocin trials should adopt a precision medicine approach. It reviews animal and human evidence on oxytocin mechanisms, intranasal delivery, social functions, and psychiatric applications, emphasizing heterogeneity and the need for targeted outcome measures.

Key findings

  • Oxytocin modulates social behavior via a social salience network including amygdala, nucleus accumbens, prefrontal cortex, insula, and other regions; effects are not uniformly prosocial and can include envy, gloating, defensive punishment, and in-group/out-group biases depending on context.
  • Intranasal delivery reaches the CNS: IN-AVP increased CSF AVP fivefold with 40 IU and tenfold with 80 IU; IN-OT (24 IU) increased CSF OT by 60% at 75 min; in monkeys, 29–36.5 IU increased CSF OT 15–30 min after intake, while 0.58–5.5 IU did not.
  • In autism spectrum disorder (ASD), plasma OT is significantly lower than in healthy subjects; IN-OT (24 IU) enhanced gaze to faces/eyes and increased ball throws toward a “good” player in an interactive social game. A meta-analysis reported associations between ASD and OTR SNPs rs7632287, rs237887, rs2268491, and rs2254298.
  • Oxytocin response varies with autism phenotype, childhood experiences, personality, attachment style, and oxytocin receptor polymorphisms, supporting targeted treatment for patient subgroups.

Methods

  • Narrative review/book chapter, not a primary empirical study; it integrates basic animal research and clinical human research on oxytocin.
  • Discusses animal methods (central injections, OTR/OT knockout mice, viral vectors, optogenetics, CRISPR), human methods (genomic analysis, postmortem brain samples, plasma/saliva/urinary OT, IN-OT, ERP, fMRI, arterial spin labeling), and behavioral assays such as the partner preference test and social ball-toss game.
  • Main analysis is a qualitative synthesis of cited literature; no systematic search, meta-analysis, or new data collection is reported.

Limitations

  • Stated: more robust OT measurement tools are needed, such as mass spectrometry, and the correlation between peripheral and central OT actions remains incompletely understood.
  • Stated: human OTR distribution knowledge relies solely on postmortem studies and autoradiography; clinical trials need more objective outcome measures, hypothesis-driven studies, replications, and better animal assays that model autism heterogeneity.
  • Evident: as a narrative chapter, it does not report a systematic review protocol, risk-of-bias assessment, or quantitative synthesis; conclusions rely on selected cited studies.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/7854_2017_29

Cites

151 of 151 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 163 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    A potent and selective oxytocin receptor antagonist evaluated in nonhuman primates mildly penetrated the brain.

    “Our group evaluated a potent and selective oxytocin receptor antagonist in nonhuman primate and showed that it mildly penetrated the brain (Smith et al. 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Smith et al. 2016

      Not checked in the free run.

  • Findingcitation

    OT plays an important role in coordinating brain activity of several regions relevant to reward and perceptual circuitry (NAcc, PFC, PVN, amygdala, and olfactory bulb) in prairie voles after mating.

    “In addition to the role of OT in NAcc and PFC in the formation of bonds, our lab recently showed that OT plays an important role in coordinating the brain activity of several regions relevant to reward and perceptual circuitry (such as NAcc, PFC, PVN, amygdala, and olfactory bulb) in prairie voles after mating (Johnson et al. 2016a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Johnson et al. 2016a

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  • Findingcitation

    Consolation can be abolished in prairie voles with administration of a selective OT antagonist in the ACC.

    “Importantly, we found that consolation can be abolished in prairie voles with the administration of a selective OT antagonist in the ACC, a region involved in empathy and salience in humans (Singer et al. 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Singer et al. 2004 source

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  • Findingown data

    Rodents are able to display instinctive consoling responses toward a stressed cagemate or a partner.

    “Recently, we have demonstrated that rodents are also able to display instinctive consoling responses toward a stressed cagemate or a partner.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    OT acts in the medial amygdala during initial exposure to other conspecifics to facilitate social recognition.

    “In a subsequent study (Ferguson et al. 2001), we found that OT acts in the medial amygdala during initial exposure to other conspecifics to facilitate social recognition.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ferguson et al. 2001 source

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  • May combine two claims. 41
  • Classified as probably not a substantial claim. 12

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    Findingown data

    Both wild-type and OTKO mice show induction of Fos activity in olfactory bulb, piriform, cortical amygdala, and lateral septum, but not in medial amygdala following social recognition.

    “Using c-Fos immunoreactivity as a marker of neural activation, we showed that while both wild-type and OTKO mice show an induction of Fos activity in the olfactory bulb, piriform, cortical amygdala, and lateral septum, they do not exhibit an induction in the medial amygdala following social recognition.”
    Quote in the paperSubstantial claim

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    Findingcitation

    Intranasal administration (24 IU) of OT to adults with ASD (men between 18 and 45 years old) enhanced their attention to faces and improved social recognition of implicit cues within an interactive social game in a within-subject placebo-controlled study.

    “In terms of exogenous effects of OT, we showed that intranasal administration (24 IU) of OT to adults with ASD (men between 18 and 45 years old) enhanced their attention to faces and improved the social recognition of implicit cues within an interactive social game in a within subject placebo-controlled study (Andari et al. 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Andari et al. 2010 source

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    Findingnone given

    IN-OT reduced amygdala and hippocampal activity during the social ball-game in a context-dependent fashion and increased activity of orbitofrontal and insula regions during interaction with fair and unfair player.

    “IN-OT reduced amygdala and hippocampal activity during the social ball-game in a context-dependent fashion and increases the activity of orbitofrontal and insula regions during the interaction with the fair and the unfair player.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin increases cooperation and trust in others, but also envy and gloating during loss and defensive responses and punishment for the out-group during threatening conditions.

    “Researchers have found that OT increases cooperation and trust in others, but also envy and gloating during the experience of loss and defensive responses and punishment for the out-group during threatening conditions (De Dreu et al. 2010; Kosfeld et al. 2005; Shamay-Tsoory et al. 2009).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites De Dreu et al. 2010 source

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    • cites Kosfeld et al. 2005 source

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    • cites Shamay-Tsoory et al. 2009 source

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    Premisecitation

    Rhesus macaques exhibit oxytocin receptor expression in visual processing areas, while the more highly social marmoset macaques have dense oxytocin receptors in reward brain regions such as the nucleus accumbens.

    “While rhesus macaques exhibit OTR expression in areas relevant to visual processing (such as the nucleus basalis of Meynert or NBM), the more highly social marmoset macaques have dense OTR in reward brain regions such as the NAcc (Freeman and Young 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Freeman and Young 2016

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    Premisecitation

    The peptide structure and neuronal system of oxytocin and its homologs remained relatively conserved across species over 600 million years, but its receptor expression is evolutionarily diverse and varies with socio-behavioral diversity.

    “The peptide structure and the neuronal system of oxytocin along with its homologs remained relatively conserved across species over 600 million years, but its receptor expression is evolutionarily diverse and varies in relation to socio-behavioral diversity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gruber 2014 source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Oxytocin effects on social behavior and brain function vary between individuals based on external factors such as autism phenotype heterogeneity, childhood experiences, personality, attachment style, and oxytocin receptor polymorphisms.

    “Oxytocin effects on social behavior and brain function can vary from one individual to another based on external factors, such as heterogeneity in autism phenotype, childhood experiences, personality, attachment style, and oxytocin receptor polymorphisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Targeted therapies for subgroups of patients can help alleviate some core symptoms and lead to a better future for these patients and their families.

    “Hence, targeted therapies for subgroups of patients can help alleviating some of the core symptoms and lead to a better future for these patients and their families.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin promotes social functioning in patients with autism spectrum disorder and reduces anxiety in patients with anxiety-related disorders.

    “Today, we have accumulated evidence for the effects of IN-OT in promoting social functioning in ASD (Andari et al. 2010, 2016) and in reducing anxiety in patients with anxiety-related disorders.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Andari et al. 2010, 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    Knowledge about oxytocin receptor distribution in human brains relies solely on postmortem studies and autoradiography.

    “Our knowledge about OTR distribution in human brains relies solely on postmortem studies and autoradiography.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The difference in oxytocin receptor distribution in the brain between species shapes behavioral aptitudes in processing social cues.

    “The difference in OTR distribution in the brain between different species shapes behavioral aptitudes in processing social cues.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In humans, systemically administered oxytocin can have side effects by acting on peripheral organs and does not cross the blood-brain barrier to yield neurobehavioral effects.

    “In humans, when administered systemically, OT can have side effects by acting on peripheral organs and it does not cross the BBB to yield neurobehavioral effects.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    There are several controversies regarding the validity of peripheral oxytocin measurements.

    “Currently, there are several controversies regarding the validity of OT peripheral measurements.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Genetic variants or plasma oxytocin are associated with variance in social cognition.

    “Genetic variants or plasma oxytocin are associated with the variance in social cognition.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Debate surrounding the use of immunoassay methods with or without extraction of oxytocin leads to controversial results in some cases.

    “There is a debate surrounding the use of immunoassay methods such as enzyme immunoassay or radioimmunoassay with or without extraction of OT, which leads to controversial results in some cases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Because primates and humans are visual, oxytocin might act on oxytocin receptors in attention and visual areas to increase attention to social cues.

    “Given that primates and humans are visual, OT might act on OTRs in attention and visual areas to increase attention to social cues.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The function of oxytocin is not a simple formula leading to one outcome with positive or negative valence; it is complex and depends on multiple factors.

    “Thus, the function of oxytocin is not a simple formula that leads to one outcome with a positive valence or a negative valence: f(OT) = Xi + R+ or f(OT) = Xi + R− (in which X stands for subject and R for response).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    In humans, oxytocin receptors are observed in abundance in the nucleus basalis of Meynert and diagonal band of Broca, with less intense binding in the medial septal nucleus, globus pallidus, and ventral pallidum.

    “In humans, OTR are observed in abundance in the NBM and diagonal band of Broca, with less intense binding in the medial septal nucleus, globus pallidus, and ventral pallidum.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    There is likely a coordinated evoked release of oxytocin in the brain and periphery, and peripheral measurements of oxytocin during social or sexual events can to some extent reflect oxytocin function in the brain.

    “This suggests that there is likely a coordinated evoked release of OT in the brain and the periphery, and that peripheral measurements of OT levels during social or sexual events can, to some extent, reflect OT function in the brain.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The oxytocin system underwent adaptive transformations in its axonal projections and receptor distribution in the brain, shaping the evolution of complex social behaviors.

    “Despite some conserved functions of the OT system, it underwent several adaptive transformations in its axonal projections and its receptor distribution in the brain, shaping the evolution of complex social behaviors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Mean cerebrospinal fluid concentrations began to rise within 10 minutes of intranasal administration and stayed above placebo groups 100 to 120 minutes after intake.

    “Mean CSF concentrations began to rise within 10 min of intranasal administration and stayed above those in placebo groups 100–120 min after intake.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Born et al. 1986 source

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    Premisecitation

    In mice and rats, intranasal oxytocin increased oxytocin content within the dorsal hippocampus and amygdala, with peak activity between 30 and 60 minutes after spray intake.

    “In mice and rats, IN-OT increased OT content within the dorsal hippocampus and amygdala (Neumann et al. 2013), with peak activity between 30 and 60 min after spray intake, very similar to human findings.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Neumann et al. 2013 source

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    Premisecitation

    Intravenous administration of vasopressin enhanced plasma vasopressin but did not affect brain activity measured by event-related potentials.

    “More importantly, intravenous administration of AVP enhanced plasma AVP but did not affect the brain activity (measured by ERP) (Pietrowsky et al. 1989), showing that the effects after IN-AVP are not dependent on the AVP plasma concentration.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pietrowsky et al. 1989 source

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  • May combine two claims.

    Premisecitation

    In humans, a number of studies showed that intranasal oxytocin or intranasal vasopressin affects brain activity and enhances oxytocin or vasopressin levels in cerebrospinal fluid.

    “In humans, a number of studies showed that IN-OT or intranasal administration of AVP (IN-AVP) affects brain activity and enhances OT or AVP levels in the cerebrospinal fluid (CSF), respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In monkeys, a small dose of intranasal oxytocin between 0.58 and 5.5 IU did not increase cerebrospinal fluid oxytocin, while a larger dose between 29 and 36.5 IU increased cerebrospinal fluid oxytocin 15 to 30 minutes after spray intake.

    “Authors reported that while a small dose of IN-OT (between 0.58 and 5.5 IU) did not increase CSF OT, a bigger dose that is frequently used in human trials (between 29 and 36.5 IU) increases CSF OT 15–30 min following spray intake (Freeman et al. 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Freeman et al. 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Natural variations in the expression of neurobehavioral changes within species can vary from one individual to another in terms of reception of parental care early in development, depending on genetic predispositions and early-life environment.

    “Several lines of research have also shown that there are natural variations in the expression of these neurobehavioral changes within species that can vary from one individual to another in terms of reception of parental care early in development, depending on genetic predispositions and early-life environment.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    In addition to its peripheral effects, oxytocin plays a key role in orchestrating complex social behaviors such as maternal attachment, pair bond formation, prosociality, reduction of stress and anxiety, and social cognition through its release in the brain and actions as a neuromodulator.

    “In addition to the known peripheral effects of OT, this molecule plays a key role in orchestrating complex social behaviors, such as maternal attachment, pair bond formation, prosociality, reduction of stress and anxiety, and social cognition, through its release in the brain and its actions as a neuromodulator.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    OTRKO dams display robust impairments in maternal care and longer latencies to retrieve pups.

    “For instance, OTRKO dams are still able to give birth but display robust impairments in maternal care and longer latencies to retrieve the pups (Takayanagi et al. 2005).”
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    • cites Takayanagi et al. 2005 source

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    Premisecitation

    Synchrony and balance between social brain networks are necessary to ensure optimal emotional responsiveness and emotion regulation.

    “A synchrony and balance between all these social brain networks are necessary to ensure optimal emotional responsiveness and emotion regulation (Feldman 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Feldman 2015 source

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    Premisecitation

    OT peripheral levels are associated with quality of mother-infant or father-infant interaction, affectionate contact, engagement, and affect synchrony.

    “OT peripheral levels are associated with the quality of mother–infant or father–infant interaction, affectionate contact, engagement, and affect synchrony (Feldman et al. 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Feldman et al. 2010 source

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  • May combine two claims.

    Interpretationreasoning

    OTR in the NAcc are relevant during development and the early phase of mother-infant interaction, which can later shape nurturing behavior in adulthood.

    “This suggests that the existence of these OTR in the NAcc is relevant during development and the early phase of mother–infant interaction, which can later shape the nurturing behavior in adulthood.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    OT is essential for consolation behavior and emotional empathy in rodents.

    “This demonstration shows that OT is essential for consolation behavior and emotional empathy in rodents.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    More grooming is observed in response to familiar conspecifics compared to strangers, resulting in a familiarity bias.

    “More grooming was observed in response to familiar conspecifics compared to strangers, resulting in a familiarity bias.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Burkett et al. 2016 source

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    Premisecitation

    IN-OT can enhance empathy in Israeli Jewish participants toward the pain of Palestinians, reducing the effect of in-group empathy bias observed in the placebo.

    “IN-OT can also enhance empathy in Israeli Jewish participants toward the pain of Palestinians, reducing the effect of in-group empathy bias observed in the placebo (Shamay-Tsoory et al. 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Shamay-Tsoory et al. 2013 source

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    Premisecitation

    OTKO mice are able to recognize nonsocial olfactory scents, making their deficit selectively a social recognition deficit.

    “However, these OTKO mice are able to recognize nonsocial olfactory scents, which make their deficit selectively a social recognition deficit.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ferguson et al. 2000 source

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    Premisecitation

    IN-OT promotes social exploration, enhances social motivation, and attenuates social vigilance in nonhuman primate models.

    “There is accumulated research on the role of IN-OT in promoting social exploration, enhancing social motivation and attenuating social vigilance in nonhuman primate models (Chang et al. 2012; Chang and Platt 2014; Ebitz and Platt 2013; Parr et al. 2013; Putnam et al. 2016).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chang et al. 2012 source

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    • cites Chang and Platt 2014 source

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    • cites Ebitz and Platt 2013 source

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  • May combine two claims.

    Premisecitation

    Cntnap2 knockout mice display social deficits in addition to epilepsy and cortical dysplasia and show a reduction in neurons expressing OT in the PVN.

    “These mice display social deficits in addition to epilepsy and cortical dysplasia and show a reduction in neurons expressing OT in the PVN.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Penagarikano et al. 2015 source

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  • May combine two claims.

    Premisecitation

    Oxytocin treatment in the embryonic period suppresses GABA-mediated excitation in mice, and these effects were blocked by infusion of an OTR antagonist.

    “Tyzio et al. (2014) showed that oxytocin treatment in the embryonic period suppresses GABA-mediated excitation in mice and that these effects were blocked by the infusion of an OTR antagonist (Tyzio et al. 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tyzio et al. 2014 source

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    Premisecitation

    Oxytocin modulates neural activity by affecting excitatory/inhibitory balance and improves signal-to-noise ratio by stimulating fast spiking parvalbumin interneuron activity.

    “Oxytocin is thought to modulate neural activity by affecting the excitatory/inhibitory balance and also seems to improve the signal-to-noise ration by stimulating fast spiking parvalbumin inter-neuron activity (Owen et al. 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Owen et al. 2013 source

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    Premisecitation

    Optogenetic activation of OT terminals in central amygdala reduces freezing in fear-conditioned animals, and injection of an OTR antagonist restores freezing behavior.

    “Optogenetic activation of OT terminals in the central amygdala reduces freezing in fear-conditioned animals and injection of an OTR antagonist restores the freezing behavior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Knobloch et al. 2012 source

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    Premisecitation

    Subjects who received both OT and social support exhibited the lowest cortisol concentrations and displayed decreased anxiety during the Trier Social Stress Test.

    “In early studies, researchers documented the anxiolytic effect of IN-OT (24 IU) and showed that subjects who received both OT and social support exhibited the lowest cortisol concentrations and displayed decreased anxiety during the Trier Social Stress Test (Heinrichs et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Heinrichs et al. 2003 source

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  • May combine two claims.

    Premisecitation

    IN-OT increases gaze time or visual fixation toward the eye region and the face.

    “IN-OT increases gaze time or visual fixation toward the eye region and the face (Auyeung et al. 2015; Domes et al. 2013; Guastella et al. 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Auyeung et al. 2015 source

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    • cites Domes et al. 2013 source

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    • cites Guastella et al. 2008 source

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  • May combine two claims.

    Premisecitation

    IN-OT increases cooperation and social trust in others.

    “Researchers found that IN-OT increases cooperation and social trust in others (Kosfeld et al. 2005), increases envy and schadenfreude in situations of loss (Shamay-Tsoory et al. 2009), enhances mind-reading capacities (Domes et al. 2007b), increases memory for faces (Rimmele et al. 2009), and improves emotion recognition (Schulze et al. 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kosfeld et al. 2005 source

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  • May combine two claims.

    Premisecitation

    While hearing infant's laughter, IN-OT reduces activation of amygdala and enhances functional connectivity between amygdala and OFC, ACC, hippocampus, and precuneus.

    “While hearing infant’s laughter, IN-OT reduces the activation of the amygdala and enhances the functional connectivity between the amygdala and the OFC, ACC, hippocampus, and precuneus (Riem et al. 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Riem et al. 2012 source

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  • May combine two claims.

    Premisecitation

    Plasma oxytocin concentration and OTR polymorphisms correlate with social aptitudes in children with and without autism.

    “Recently, Parker et al. (2014) reported that plasma oxytocin concentration and OTR polymorphisms correlate with social aptitudes in children with and without autism (Parker et al. 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Parker et al. 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IN-OT enhances socially reinforced learning and emotional empathy.

    “Hurlemann et al. (2010) showed that IN-OT enhances socially reinforced learning and emotional empathy (Hurlemann et al. 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hurlemann et al. 2010 source

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  • May combine two claims.

    Interpretationreasoning

    When treated with IN-OT, participants with ASD were able to recognize implicit social cues during the social game, display appropriate emotional responses toward players, and respond appropriately based on different social profiles.

    “Hence, when treated with IN-OT, participants with ASD were able to recognize implicit social cues during the social game, display appropriate emotional responses toward players, and respond appropriately based on the different social profiles of the different players.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    IN-OT enhances emotion recognition and theory of mind in ASD.

    “IN-OT enhances emotion recognition and theory of mind in ASD (Aoki et al. 2014; Guastella et al. 2010), and gaze to the eyes in ASD and in healthy subjects (Auyeung et al. 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Aoki et al. 2014 source

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    • cites Guastella et al. 2010 source

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  • May combine two claims.

    Interpretationreasoning

    Low baseline OT levels are not necessarily a biomarker of social dysfunctions in ASD, but instead a general biomarker of sociability.

    “Thus, low baseline OT levels are not necessarily a biomarker of social dysfunctions in ASD, but instead a general biomarker of sociability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OT reduces anxiety, fear, and stress, in part by dampening amygdala activity.

    “there are increasing evidence for the role of OT in reducing anxiety, fear, and stress, in part by dampening amygdala activity”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Bethlehem et al. 2013 source

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    • cites Domes et al. 2007a

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    • cites Labuschagne et al. 2010 source

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  • May combine two claims.

    Premisecitation

    The improvement was accompanied by increased resting state functional connectivity between ACC and dmPFC and increased eye gaze during a social-judgment task.

    “The improvement was accompanied by increased resting state functional connectivity between ACC and dmPFC in addition to an increased eye gaze during a social-judgment task.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Watanabe et al. 2015 source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Heterogeneity may be the reason that the outcome of the majority of drug-based clinical trials represents small-to-moderate effect sizes or negative results and lack of replications.

    “Heterogeneity may be precisely the reason that the outcome of the majority of drug-based clinical trials represents small-to-moderate effect sizes or to negative results and lack of replications.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Anxiety symptoms and social disorders are highly complex and vary from one individual to another, even within the same disorder.
52 of 52

  • The paper relies on this without support.

    The neurobehavioral functions of OT observed in animal species are conserved in humans.

    “We believe that the neurobehavioral functions of OT observed in animal species are also conserved in humans, and that healthy bonds with partners are essential to reduce the risk of mental disorders and health-related issues.”

  • The paper relies on this without support.

    Species-specific social behaviors are generated by a brain hardwired for affiliation and attachment.

    “These species-specific behaviors are generated by a brain hardwired for affiliation and attachment.”

  • The paper relies on this without support.

    Pair bonds or social bonds in general are essential for a better healthy life.

    “Pair bonds or social bonds in general are essential for a better healthy life.”

  • The paper relies on this without support.

    Currently, to determine that a particular rodent model with a particular gene manipulation is an animal model of autism, the animal needs to fail the simple social interaction or social discrimination task and display less social approach.

    “currently, in order to determine that a particular rodent model with a particular gene manipulation is an animal model of autism, the animal needs to fail the simple social interaction or social discrimination task and display less social approach.”

  • The paper relies on this without support.

    Anxiety symptoms and social disorders are highly complex and vary from one individual to another, even within the same disorder.

    “Anxiety symptoms (including traits of anxiety, generalized anxiety disorder, social anxiety disorder, and posttraumatic stress disorder) as well as social disorders (including lack of emotional and cognitive empathy, lack of intuitive understanding of others’ hidden intentions, and social reciprocity) are highly complex and vary from one individual to another, even within the same disorder.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Interpersonal-distance effect reverses the cited study's direction

    Minor

    The text says oxytocin enhances interpersonal distance among highly empathic people, implying greater distance. The cited reference instead describes oxytocin as promoting closer interpersonal distance in that group.

1 of 1

Cites

Flagged first, then by citations

1 of the 152 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Andari, E., Hurlemann, R., & Young, L. J.
Affiliations
Emory University (US)
Corresponding author
Andari, Elissar
ORCID
Venue
Current Topics in Behavioral Neurosciences
Publisher
Springer International Publishing
Published
2017
Volume
35
Pages
559-590
ISSN
  • 1866-3370 (ISSN-L)
  • 1866-3389
DOI
10.1007/7854_2017_29
PMC
PMC5815942
OpenAlex
W2747561319
Semantic Scholar
748563cf3b4bf55f10de880a1cefce6ae056c00c
Cited by
40
References
152
Citations by year
2026: 3 · 2025: 4 · 2024: 1 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 2 · 2018: 5
FWCI
18.99
Type
book chapter
Language
en
Open access
Licence
www.springer.com/tdm (unspecified)
Locations
  • Current topics in behavioral neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (P51OD011132)
  • National Institute of Mental Health (P50MH100023)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin, precision medicine, neuromodulators, social behavior, anxiety disorders, autism spectrum disorder, epigenetics, social brain network, targeted therapy, neuropsychiatric disorders, attachment styles, childhood experiences
MeSH terms
Anxiety Disorders, Autistic Disorder, Brain, Clinical Trials as Topic, Fear, Humans, Oxytocin, Social Behavior, Precision Medicine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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