Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction
Open accessAbstract
Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.
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Male bias can be observed in much of prior work on oxytocin in humans.
“This bias can be observed in much of the prior work on oxytocin in humans as well, with some neuroimaging studies indicating potential differences in the oxytocin system between sexes.13, 14, 47, 48, 49”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [48]
Some neuroimaging studies indicate potential differences in the oxytocin system between sexes.
“This bias can be observed in much of the prior work on oxytocin in humans as well, with some neuroimaging studies indicating potential differences in the oxytocin system between sexes.13, 14, 47, 48, 49”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [48]
OT and AVP can have differential effects on neural activity (BOLD fMRI responses) and cognition, at least in some cases, although the effects of OT are more robust.
“These data have, however, found OT and AVP can have differential effects on neural activity (i.e., BOLD fMRI responses) and cognition, at least in some cases although the effects of OT are more robust [84; 86; 87; 88; 89; 90].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [88]
The few studies that have compared the effects of intranasally administered OT and AVP in humans have reported that these peptides do not have opposing roles.
“The few studies that have compared the effects of intranasally administered OT and AVP in humans have reported that these peptides do not have opposing roles.”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [88]
In humans, intranasal VP has sex-specific effects during social communication and cooperation interactions.
“In humans, intranasal VP had sex-specific effects during social communication and cooperation interactions”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Rilling et al., 2014
Intranasal OT increased caudate/putamen response in males, whereas it decreased this response in females.
“Intranasal OT increased the caudate/putamen response in males, whereas it decreased this response in females (Rilling et al., 2014).”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Rilling et al., 2014
Sex differences were found for the effect of OT on brain activation during reciprocated cooperation.
“Sex differences were also found for the effect of OT on brain activation during reciprocated cooperation.”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Rilling et al., 2014
Oxytocin effects can vary as a function of sex.
“previous research has shown that oxytocin effects can vary as a function of emotion regulation skills (Quirin et al., 2011), social context history of childhood maltreatment (Ebert et al., 2013; Flanagan et al., 2015), and sex (Ditzen et al., 2012; Rilling et al., 2014).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Rilling et al., 2014
In healthy individuals, OT effects seem to follow an inverted u-shape, with doses around 24 IU resulting in more anxiolytic effects than higher doses.
“In healthy individuals, OT effects seem to follow an inverted u-shape (Rilling et al, 2014), with doses ~24 IU, resulting in more anxiolytic effects than higher doses of OT (Cardoso et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Rilling et al, 2014
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Cites
Axelrod, R., & Hamilton, W. D. (1981) · Science · doi:10.1126/science.7466396 · Cited by 20,065 · see citing works
Advances in functional and structural MR image analysis and implementation as FSL
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., De Luca, M., Drobnjak, I., Flitney, D. E., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.051 · Cited by 13,630 · see citing works
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798 · see citing works
The Evolution of Reciprocal Altruism
Trivers, R. L. (1971) · The Quarterly Review of Biology · doi:10.1086/406755 · Cited by 11,010 · cited 4× · see citing works
“The iterated Prisoner’s Dilemma game is a model for relationships based on reciprocal altruism (Trivers, 1971).”
BackgroundMethodInfluentialOxytocin increases trust in humans
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005) · Nature · doi:10.1038/nature03701 · Cited by 3,690 · cited 2× · see citing works
“It has been shown to do so in other experimental contexts (Baumgartner et al., 2008; De Dreu, 2012a,b; Israel et al., 2012; Kosfeld et al., 2005).”
BackgroundForman, S. D., Cohen, J. D., Fitzgerald, M., Eddy, W. F., Mintun, M. A., & Noll, D. C. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910330508 · Cited by 3,202 · cited 1× · see citing works
“05 corrected for multiple comparisons based on the volume of clusters of contiguous voxels, using a 3D extension (implemented in BrainVoyager) of a 2D Monte Carlo simulation procedure (Forman et al., 1995).”
MethodOxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688 · cited 2× · see citing works
“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”
BackgroundSocial effects of oxytocin in humans: context and person matter
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.05.002 · Cited by 1,572 · see citing works
A neural basis for social cooperation
Rilling, J. K., Gutman, D. A., Zeh, T. R., Pagnoni, G., Berns, G. S., & Kilts, C. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00755-9 · Cited by 1,451 · cited 1× · see citing works
“Within the same region of interest, defined independently of both samples using an ROI from Rilling et al (2002), we tested for drug and partner effects on the response to reciprocated cooperation among women.”
MethodSelf-citationReward representations and reward-related learning in the human brain: Insights from neuroimaging
O’Doherty, J. P. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.10.016 · Cited by 1,426 · cited 1× · see citing works
“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”
Oxytocin improves “mind-reading” in humans
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.015 · Cited by 1,298 · see citing works
Oxytocin shapes the neural circuitry of trust and trust adaptation in humans
Baumgartner, T., Heinrichs, M., Vonlanthen, A., Fischbacher, U., & Fehr, E. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.009 · Cited by 1,258 · cited 2× · see citing works
“It has been shown to do so in other experimental contexts (Baumgartner et al., 2008; De Dreu, 2012a,b; Israel et al., 2012; Kosfeld et al., 2005).”
BackgroundInsel, T. R. (2010) · Neuron · doi:10.1016/j.neuron.2010.03.005 · Cited by 1,044 · see citing works
Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962 · cited 3× · see citing works
“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”
BackgroundResultDistributed Neural Representation of Expected Value
Knutson, B., Taylor, J., Kaufman, M., Peterson, R., & Glover, G. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0642-05.2005 · Cited by 955 · cited 1× · see citing works
“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”
Reward processing in primate orbitofrontal cortex and basal ganglia
Schultz, W. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.272 · Cited by 942 · cited 1× · see citing works
“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910249107 · Cited by 941 · cited 3× · see citing works
“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”
BackgroundResultOxytocin, vasopressin, and human social behavior
Heinrichs, M., von Dawans, B., & Domes, G. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.005 · Cited by 799 · cited 1× · see citing works
“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”
BackgroundOxytocin increases gaze to the eye region of human faces
Guastella, A. J., Mitchell, P. B., & Dadds, M. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.06.026 · Cited by 798 · see citing works
Oxytocin attenuates amygdala responses to emotional faces regardless of valence
Domes, G., Heinrichs, M., Gläscher, J., Büchel, C., Braus, D. F., & Herpertz, S. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.03.025 · Cited by 774 · cited 1× · see citing works
“Sabrina Stair collected and analyzed the data.”
Champagne, F., Diorio, J., Sharma, S., & Meaney, M. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221224598 · Cited by 707 · cited 3× · see citing works
“Studies with female subjects are complicated by the fact that estradiol, levels of which vary across the menstrual cycle, is known to induce OT receptors (Champagne et al., 2001; Pedersen et al., 1994) and presumably increase responsivity to OT.”
BackgroundMethodOxytocin Increases Retention of Social Cognition in Autism
Hollander, E., Bartz, J., Chaplin, W., Phillips, A., Sumner, J., Soorya, L., Anagnostou, E., & Wasserman, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.030 · Cited by 693 · cited 1× · see citing works
“…rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women.”
BackgroundOxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders
Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronowitz, B. R., & Mosovich, S. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300021 · Cited by 689 · see citing works
Effects of intranasal oxytocin on emotional face processing in women
Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.06.016 · Cited by 521 · cited 1× · see citing works
“On the other hand, intranasal OT increased the amygdala response to fearful faces in women, but had no effect on the amygdala response to angry or happy faces (Domes et al., 2007a,b; Domes et al., 2010).”
BackgroundDifferent amygdala subregions mediate valence-related and attentional effects of oxytocin in humans
Gamer, M., Zurowski, B., & Büchel, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000985107 · Cited by 487 · cited 3× · see citing works
“The left amygdala ROI was defined as a 10 mm-side cube centered on the coordinates of the activation peak reported in Gamer et al. (Gamer et al., 2010), after converting from MNI to Talairach coordinates, and then manually adjusting the ROI location to more closely match the anatomical features of the MNI template.”
MethodInfluentialPedersen, C. A., Caldwell, J. D., Walker, C., Ayers, G., & Mason, G. A. (1994) · Behavioral Neuroscience · doi:10.1037/0735-7044.108.6.1163 · Cited by 475 · cited 3× · see citing works
“Studies with female subjects are complicated by the fact that estradiol, levels of which vary across the menstrual cycle, is known to induce OT receptors (Champagne et al., 2001; Pedersen et al., 1994) and presumably increase responsivity to OT.”
BackgroundMethodOxytocin, vasopressin, and social recognition in mammals
Bielsky, I. F., & Young, L. J. (2004) · Peptides · doi:10.1016/j.peptides.2004.05.019 · Cited by 460 · cited 2× · see citing works
“Given significant cross-reactivity between OT and AVP systems (Audigier & Barberis, 1985), coupled with evidence that OT and AVP can have similar effects on behavior (Bielsky & Young, 2004), it is important to determine whether intranasal OT and AVP activate similar or different brain regions.”
BackgroundDe Dreu, C. K. W. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.009 · Cited by 455 · see citing works
Oxytocin can hinder trust and cooperation in borderline personality disorder
Bartz, J., Simeon, D., Hamilton, H., Kim, S., Crystal, S., Braun, A., Vicens, V., & Hollander, E. (2011) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsq085 · Cited by 452 · see citing works
Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics
Manning, M., Misicka, A., Olma, A., Bankowski, K., Stoev, S., Chini, B., Durroux, T., Mouillac, B., Corbani, M., & Guillon, G. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02303.x · Cited by 423 · cited 1× · see citing works
“For example, if central AVP levels are higher in men, additional exogenous AVP could saturate AVP receptors and cross-react with OT receptors (Manning et al., 2012; Young and Flanagan-Cato, 2012) and this, in turn, could drive increases in activity in regions involved in reward and bonding.”
BackgroundLoup, F., Tribollet, E., Dubois-Dauphin, M., & Dreifuss, J. J. (1991) · Brain Research · doi:10.1016/0006-8993(91)90345-v · Cited by 378 · cited 2× · see citing works
“This activation also encompassed basal forebrain regions rich in OT receptors (Loup et al., 1991), including the preoptic area, basal nucleus of Meynert, diagonal band of Broca, and lateral septum (supplementary Table 1, Fig.”
BackgroundAnagnostou, E., Soorya, L., Chaplin, W., Bartz, J., Halpern, D., Wasserman, S., Wang, A. T., Pepa, L., Tanel, N., Kushki, A., et al. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-16 · Cited by 350 · cited 1× · see citing works
“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”
ResultDopaminergic-neuropeptide interactions in the social brain
Skuse, D. H., & Gallagher, L. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2008.09.007 · Cited by 340 · cited 2× · see citing works
“Among rodents, the social bonds supporting both maternal care and female adult partner preference are heavily dependent on interactions between OT and DA in the ventral striatum (Skuse and Gallagher, 2009; Young et al., 2005).”
BackgroundSex-specific influences of vasopressin on human social communication
Thompson, R. R., George, K., Walton, J. C., Orr, S. P., & Benson, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600406103 · Cited by 312 · cited 3× · see citing works
“However, in women, AVP enhanced affiliative facial motor patterns in response to unfamiliar female faces and increased perception of friendliness in those faces (Thompson et al., 2006).”
BackgroundResultInfluentialSelf-citationRilling, J. K., DeMarco, A. C., Hackett, P. D., Thompson, R., Ditzen, B., Patel, R., & Pagnoni, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.013 · Cited by 303 · see citing works
Albers, H. E. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.10.007 · Cited by 288 · cited 2× · see citing works
“For example, although AVP injections in the anterior hypothalamus of male hamsters stimulate aggression in the resident-intruder test, the same injections decrease aggression in females (Albers, 2012).”
BackgroundProsocial effects of oxytocin and clinical evidence for its therapeutic potential
Striepens, N., Kendrick, K. M., Maier, W., & Hurlemann, R. (2011) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.07.001 · Cited by 283 · cited 2× · see citing works
“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”
BackgroundKim, S.-J., Young, L. J., Gonen, D., Veenstra-VanderWeele, J., Courchesne, R., Courchesne, E., Lord, C., Leventhal, B. L., Cook Jr, E. H., & Insel, T. R. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001125 · Cited by 265 · cited 12× · see citing works
“In addition to ASD, studies have begun to investigate the effectiveness of intranasal OT as a treatment for schizophrenia, social anxiety disorder and depression (Striepens, et al., 2011).”
BackgroundInfluentialNonapeptide mechanisms of social cognition, behavior and species-specific social systems
Goodson, J. L., & Thompson, R. R. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.08.020 · Cited by 261 · cited 1× · see citing works
“…to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of various psychiatric disorders involving social behavioral deficits (Goodson & Thompson, 2010; MeyerLindenberg, Domes, Kirsch, & Heinrichs, 2011; Yamasue, Kuwabara, Kawakubo, & Kasai, 2009).”
BackgroundSelf-citationExamination of AVPR1a as an autism susceptibility gene
Wassink, T. H., Piven, J., Vieland, V. J., Pietila, J., Goedken, R. J., Folstein, S. E., & Sheffield, V. C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001503 · Cited by 212 · cited 12× · see citing works
“In addition to ASD, studies have begun to investigate the effectiveness of intranasal OT as a treatment for schizophrenia, social anxiety disorder and depression (Striepens, et al., 2011).”
BackgroundInfluentialDeconstructing sociality, social evolution and relevant nonapeptide functions
Goodson, J. L. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.12.005 · Cited by 206 · cited 2× · see citing works
“Our results also show that AVP can contribute to cooperation among men, and call for greater investigation of its role as a potential treatment for males with ASD, although potential pleitropic effects on stress and anxiety should be carefully investigated (Goodson, 2013; Shalev, et al., 2011).”
ResultAnatomy and neurochemistry of the pair bond
Young, L. J., Murphy Young, A. Z., & Hammock, E. A. D. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20771 · Cited by 163 · cited 2× · see citing works
“, 2006), along with evidence that AVP is more influential in males compared with females (Young et al., 2005), we did not expect AVP to augment activation in BNST, lateral septum and stria terminalis in women as it did in men.”
BackgroundAudigier, S., & Barberis, C. (1985) · The EMBO Journal · doi:10.1002/j.1460-2075.1985.tb03794.x · Cited by 156 · cited 2× · see citing works
“Given significant cross-reactivity between OT and AVP systems (Audigier & Barberis, 1985), coupled with evidence that OT and AVP can have similar effects on behavior (Bielsky & Young, 2004), it is important to determine whether intranasal OT and AVP activate similar or different brain regions.”
BackgroundDevelopmental experiences and the oxytocin receptor system
Bales, K. L., & Perkeybile, A. M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.013 · Cited by 142 · cited 2× · see citing works
“Such effects may be attributable to developmental influences on OTreceptor expression (Bales and Perkeybile, 2012), which in turn should affect responsiveness to intranasal OT.”
BackgroundDe Dreu, C. K. W. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.10.003 · Cited by 114 · see citing works
Stavropoulos, K. K. M., & Carver, L. J. (2013) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12061 · Cited by 95 · cited 4× · see citing works
“If it does the same for males with ASD, it could potentially help to normalize their social behavior by increasing their motivation to participate in and therefore learn from social interactions (Stavropoulos and Carver, 2013).”
BackgroundInfluentialOxytocin, but not vasopressin, increases both parochial and universal altruism
Israel, S., Weisel, O., Ebstein, R. P., & Bornstein, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.02.001 · Cited by 88 · see citing works
Editorial comment: Oxytocin, vasopressin and social behavior
Young, L. J., & Flanagan-Cato, L. M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.019 · Cited by 81 · cited 2× · see citing works
“For example, if central AVP levels are higher in men, additional exogenous AVP could saturate AVP receptors and cross-react with OT receptors (Manning et al., 2012; Young and Flanagan-Cato, 2012) and this, in turn, could drive increases in activity in regions involved in reward and bonding.”
BackgroundOxytocin, sexually dimorphic features of the social brain, and autism
Yamasue, H., Kuwabara, H., Kawakubo, Y., & Kasai, K. (2009) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2009.01944.x · Cited by 78 · cited 1× · see citing works
“Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of various psychiatric disorders involving social behavioral deficits (Goodson and Thompson, 2010; Meyer-Lindenberg et al., 2011; Yamasue et al., 2009).”
BackgroundNormal CSF oxytocin and NPY levels in OCD
Altemus, M. M., Jacobson, K. R., DeBellis, M. D., Kling, M. A., Pigott, T. A., Murphy, D. L., & Gold, P. W. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00263-7 · Cited by 78 · cited 2× · see citing works
“Women have higher CSF oxytocin levels than men do (Altemus et al., 1999).”
BackgroundShalev, I., Israel, S., Uzefovsky, F., Gritsenko, I., Kaitz, M., & Ebstein, R. P. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.04.005 · Cited by 65 · cited 1× · see citing works
“Our results also show that AVP can contribute to cooperation among men, and call for greater investigation of its role as a potential treatment for males with ASD, although potential pleitropic effects on stress and anxiety should be carefully investigated (Goodson, 2013; Shalev et al., 2011).”
ResultEstradiol Synthesis and Action at the Synapse: Evidence for ?Synaptocrine? Signaling
Remage‐Healey, L., Saldanha, C. J., & Schlinger, B. A. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00028 · Cited by 47 · see citing works
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The Social Salience Hypothesis of Oxytocin
Shamay-Tsoory, S. G., & Abu-Akel, A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.020 · Cited by 904 · see citing works
“indistinguishable from the baseline activation patterns in women following placebo (77).”
Empathy: Gender effects in brain and behavior
Christov-Moore, L., Simpson, E. A., Coudé, G., Grigaityte, K., Iacoboni, M., & Ferrari, P. F. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.09.001 · Cited by 1,137 · see citing works
“Importantly, both OT and AVP increased activity in males during cooperation, while in females, OT and AVP either decreased activity or had no effect in these and other regions (Rilling et al., 2014).”
BackgroundOxytocin-gaze positive loop and the coevolution of human-dog bonds
Nagasawa, M., Mitsui, S., En, S., Ohtani, N., Ohta, M., Sakuma, Y., Onaka, T., Mogi, K., & Kikusui, T. (2015) · Science · doi:10.1126/science.1261022 · Cited by 753 · see citing works
Postpartum depression: Etiology, treatment and consequences for maternal care
Brummelte, S., & Galea, L. A. M. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.08.008 · Cited by 567 · see citing works
Dumais, K. M., & Veenema, A. H. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.003 · Cited by 520 · see citing works
“Intranasal VP increased activity in areas such as the striatum, basal forebrain, insula, amygdala, and hippocampus in men, but decreased or had no effect in women (Rilling et al., 2012; 2014).”
BackgroundInfluentialThe placebo effect: From concepts to genes
Colagiuri, B., Schenk, L. A., Keßler, M., Dorsey, S. G., & Colloca, L. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.017 · Cited by 260 · see citing works
“In humans, vasopressin regulates conciliatory behaviors (Feng et al., 2014; Rilling et al., 2014) and social communication (Thompson et al.”
Song, Z., & Albers, H. E. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.10.004 · Cited by 244 · see citing works
“, BOLD fMRI responses) and cognition, at least in some cases although the effects of OT are more robust [84; 86; 87; 88; 89; 90].”
BackgroundKinetics and dose dependency of intranasal oxytocin effects on amygdala reactivity
Spengler, F. B., Schultz, J., Scheele, D., Essel, M., Maier, W., Heinrichs, M., & Hurlemann, R. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.04.015 · Cited by 229 · see citing works
“One limitation of this study is a potential sexually dimorphic effect of intranasal OXT on amygdala activation (71,72).”
BackgroundBaribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 229 · see citing works
Albers, H. E. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.07.001 · Cited by 200 · see citing works
“, 2014) and humans (Rilling et al., 2014).”
BackgroundWhy estrogens matter for behavior and brain health
Galea, L. A. M., Frick, K. M., Hampson, E., Sohrabji, F., & Choleris, E. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.024 · Cited by 180 · see citing works
“…et al. / Neuroscience and Biobe i a s l i H e r t t s i t d u ( m ( i b t H n e fi e i s t t d u r S i i H t s r e other studies (Brody et al., 2011; Rilling et al., 2014) and support ean age 21.6 yrs) (first 2 trials only; for details see Hampson and Morley, 2013; sychoneuroendocrinology, 38,…”
InfluentialOxytocin, testosterone, and human social cognition
Crespi, B. J. (2015) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12175 · Cited by 175 · see citing works
“Such sex differences, including many effects that are opposite between males and females, are commonly observed (e.g. Rilling et al., 2014), although they have yet to be systematically addressed from perspectives based on adaptive significance.”
BackgroundVascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice
Yamamoto, Y., Liang, M., Munesue, S., Deguchi, K., Harashima, A., Furuhara, K., Yuhi, T., Zhong, J., Akther, S., Goto, H., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0325-6 · Cited by 171 · see citing works
Feng, C., Hackett, P. D., DeMarco, A. C., Chen, X., Stair, S., Haroon, E., Ditzen, B., Pagnoni, G., & Rilling, J. K. (2015) · Brain Imaging and Behavior · doi:10.1007/s11682-014-9333-9 · Cited by 157 · see citing works
Bredewold, R., Smith, C. J. W., Dumais, K. M., & Veenema, A. H. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00216 · Cited by 157 · see citing works
Rutigliano, G., Rocchetti, M., Paloyelis, Y., Gilleen, J., Sardella, A., Cappucciati, M., Palombini, E., Dell’Osso, L., Caverzasi, E., Politi, P., et al. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.04.117 · Cited by 149 · see citing works
“ADH has been shown to alter reciprocation of cooperation in males (Rilling et al., 2014) while the ADH Avpr-1a gene, which is involved in social bonding in humans (Walum et al., 2008), has been shown to influence the money people will give to others in an economic game (Knafo et al., 2008).”
Sex and gender differences in the development of empathy
Rochat, M. J. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25009 · Cited by 156 · see citing works
“…humans, several studies have identified a role for the oxytocinergic and the fetal testosterone systems in modulating empathy (Chapman et al., 2006; Rilling et al., 2014, but see Nadler et al., 2019 for contrasting results), while animal models enhance the role of gonadal hormones on sexually…”
ResultBredewold, R., & Veenema, A. H. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.011 · Cited by 144 · see citing works
Ma, Y., Shamay-Tsoory, S., Han, S., & Zink, C. F. (2016) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.10.009 · Cited by 131 · see citing works
“, cooperation [52,77], social feedback [58], infant and sexual pictures [81], and happy faces [42]).”
BackgroundOxytocin, vasopressin, and the motivational forces that drive social behaviors
Caldwell, H. K., & Albers, H. E. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_390 · Cited by 129 · see citing works
Bolognani, F., del Valle Rubido, M., Squassante, L., Wandel, C., Derks, M., Murtagh, L., Sevigny, J., Khwaja, O., Umbricht, D., & Fontoura, P. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat7838 · Cited by 128 · see citing works
Oxytocin and Estrogen Receptor β in the Brain: An Overview
Acevedo-Rodriguez, A., Mani, S. K., & Handa, R. J. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00160 · Cited by 124 · see citing works
“Female rats were found to have fewer OTRs in the BNST, VMH, and medial amygdala compared to males (24), and in humans, men and women were found to respond differently to intranasal OT administration (25, 26).”
BackgroundGrace, S. A., Rossell, S. L., Heinrichs, M., Kordsachia, C., & Labuschagne, I. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.031 · Cited by 120 · see citing works
“Addditionally, increased functional connectivity of the insula was also observed in four studies (Gorka et al., 2015; Hu et al., 2015; Rilling et al., 2014; Rilling et al., 2012).”
InfluentialHormonal contraceptives suppress oxytocin-induced brain reward responses to the partner’s face
Scheele, D., Plota, J., Stoffel-Wagner, B., Maier, W., & Hurlemann, R. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsv157 · Cited by 116 · see citing works
“However, in light of accumulating evidence implying sexual-dimorphic effects of OXT on reproductive behavior, social cognition and emotional processing (Domes et al., 2010; Lischke et al., 2012; Fischer-Shofty et al., 2013; Lynn et al., 2014; Preckel et al., 2014; Rilling et al., 2014; Scheele et al., 2014b; Yao et al…”
BackgroundFlanagan, J. C., Sippel, L. M., Wahlquist, A., Moran-Santa Maria, M. M., & Back, S. E. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.12.014 · Cited by 117 · see citing works
“For example, previous research has shown that oxytocin effects can vary as a function of emotion regulation skills (Quirin et al., 2011), social context history of childhood maltreatment (Ebert et al., 2013; Flanagan et al., 2015), and sex (Ditzen et al., 2012; Rilling et al., 2014).”
Oxytocin facilitates social approach behavior in women
Preckel, K., Scheele, D., Kendrick, K. M., Maier, W., & Hurlemann, R. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00191 · Cited by 111 · see citing works
Opposing effects of oxytocin on moral judgment in males and females
Scheele, D., Striepens, N., Kendrick, K. M., Schwering, C., Noelle, J., Wille, A., Schlaepfer, T. E., Maier, W., & Hurlemann, R. (2014) · Human Brain Mapping · doi:10.1002/hbm.22605 · Cited by 112 · see citing works
“Sex-dimorphic effects of OXT have been reported in several previous studies [Domes et al., 2010; Preckel et al., 2014; Rilling et al., 2014] and might be related to sex differences in human OXT receptor distributions.”
ResultVasopressin Boosts Placebo Analgesic Effects in Women: A Randomized Trial
Colloca, L., Pine, D. S., Monique Ernst, D., Miller, F. G., & Grillon, C. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.019 · Cited by 110 · see citing works
“Vasopressin increased the probability to cooperate as second player in women but not in men following a partner defection, favoring conciliatory gesture and cooperation (24).”
BackgroundIntranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women
Bethlehem, R. A. I., Lombardo, M. V., Lai, M.-C., Auyeung, B., Crockford, S. K., Deakin, J., Soubramanian, S., Sule, A., Kundu, P., Voon, V, et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.72 · Cited by 96 · see citing works
Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities
Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M. (2017) · Chronic Stress · doi:10.1177/2470547016687996 · Cited by 99 · see citing works
Koch, S. B., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.299 · Cited by 98 · see citing works
Feng, C., Lori, A., Waldman, I. D., Binder, E. B., Haroon, E., & Rilling, J. K. (2015) · Genes, Brain and Behavior · doi:10.1111/gbb.12234 · Cited by 94 · see citing works
“One possible explanation for our observed sex differences in the effect of OT on brain activity could be that the dose–response function between brain OT levels and neural activity follows an inverted-U shape (Cardoso et al. 2013, 2014; Rilling et al. 2014).”
BackgroundMethodInfluentialSelf-citationKinetics of oxytocin effects on amygdala and striatal reactivity vary between women and men
Lieberz, J., Scheele, D., Spengler, F. B., Matheisen, T., Schneider, L., Stoffel‐Wagner, B., Kinfe, T. M., & Hurlemann, R. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0582-6 · Cited by 93 · see citing works
The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans
Kerem, L., & Lawson, E. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147737 · Cited by 94 · see citing works
Wang, D., Yan, X., Li, M., & Ma, Y. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx085 · Cited by 86 · see citing works
“…on STG activity might be independent of the valence of the processes, as we found that IN-OT increased STG activity was contributed by studies examining positive (Voorthuis et al., 2014; Rilling et al., 2014) or negative processes (Domes et al., 2010; Riem et al., 2011; Lischke et al., 2012).”
BackgroundInfluentialLinks between the neurobiology of oxytocin and human musicality
Harvey, A. R. (2020) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.00350 · Cited by 85 · see citing works
The promises and pitfalls of sex difference research
Galea, L. A. M., Choleris, E., Albert, A., McCarthy, M. M., & Sohrabji, F. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100817 · Cited by 85 · see citing works
Oxytocin’s effect on resting-state functional connectivity varies by age and sex
Ebner, N. C., Chen, H., Porges, E., Lin, T., Fischer, H., Feifel, D., & Cohen, R. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.03.013 · Cited by 84 · see citing works
“, 2015a) and sex variations in the effects, some of which ave supported sex differences (Lischke et al., 2012; Domes et al., 010; Rilling et al., 2014) and some of which have not (Ellenbogen t al.”
BackgroundInfluentialDai, Y., Zhang, H., Schön, M., Böckers, T. M., Han, S., Han, J., & Zhang, R. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00355 · Cited by 82 · see citing works
“In clinical studies, OXT treatment for patients with ASD is mostly concentrated during adolescence or adulthood, with a demonstrable therapeutic effect (Hollander et al., 2003; Hollander et al., 2007; Andari et al., 2010; Guastella et al., 2010; Hall et al., 2012; Rilling et al., 2014).”
BackgroundLonstein, J. S., Maguire, J. L., Meinlschmidt, G., & Neumann, I. D. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12188 · Cited by 83 · see citing works
Frijling, J. L. (2017) · European Journal of Psychotraumatology · doi:10.1080/20008198.2017.1302652 · Cited by 84 · see citing works
Chen, X., Hackett, P. D., DeMarco, A. C., Feng, C., Stair, S., Haroon, E., Ditzen, B., Pagnoni, G., & Rilling, J. K. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-015-9411-7 · Cited by 81 · see citing works
“We have also previously reported OT and AVP modulation of the BOLD fMRI response to positive social interactions (reciprocated cooperation in the PD game), using a sub-set of the sample reported here (Rilling et al. 2014).”
Self-citationOxytocin facilitates reciprocity in social communication
Spengler, F. B., Scheele, D., Marsh, N., Kofferath, C., Flach, A., Schwarz, S., Stoffel‐Wagner, B., Maier, W., & Hurlemann, R. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx061 · Cited by 80 · see citing works
“As a substantial body of evidence now points to sexual-dimorphic effects of OXT (Preckel et al., 2014; Rilling et al., 2014; Scheele et al., 2014), we cannot extrapolate our findings to women.”
BackgroundEbner, N. C., Lin, T., Muradoglu, M., Weir, D. H., Plasencia, G. M., Lillard, T. S., Pournajafi-Nazarloo, H., Cohen, R. A., Sue Carter, C., & Connelly, J. J. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2018.01.008 · Cited by 79 · see citing works
How the brain codes intimacy: The neurobiological substrates of romantic touch
Kreuder, A.-K., Scheele, D., Wassermann, L., Wollseifer, M., Stoffel-Wagner, B., Lee, M. R., Hennig, J., Maier, W., & Hurlemann, R. (2017) · Human Brain Mapping · doi:10.1002/hbm.23679 · Cited by 89 · see citing works
“Specifically, intranasal OXT enhanced striatal responses to reciprocated cooperation in a Prisoner’s Dilemma Game in men, but not in women [Rilling et al., 2014].”
BackgroundSex-Related Differences in Plasma Oxytocin Levels in Humans
Marazziti, D., Baroni, S., Mucci, F., Piccinni, A., Moroni, I., Giannaccini, G., Carmassi, C., Massimetti, E., & Dell’Osso, L. (2019) · Clinical Practice and Epidemiology in Mental Health · doi:10.2174/1745017901915010058 · Cited by 80 · see citing works
Pupil-mimicry conditions trust in partners: moderation by oxytocin and group membership
Kret, M. E., & De Dreu, C. K. W. (2017) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2016.2554 · Cited by 75 · see citing works
Oxytocin makes females, but not males, less forgiving following betrayal of trust
Yao, S., Zhao, W., Cheng, R., Geng, Y., Luo, L., & Kendrick, K. M. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571400090x · Cited by 74 · see citing works
“, 2010) and during social cooperation interactions (Rilling et al., 2014).”
BackgroundIntranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder
Nawijn, L., van Zuiden, M., Koch, S. B. J., Frijling, J. L., Veltman, D. J., & Olff, M. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw123 · Cited by 72 · see citing works
“Taken together, our and previous findings fit with the notion that neural effects of oxytocin administration depend on individual factors such as patient status, sex or other individual characteristics, but only if these factors are related to differences in baseline functioning (Labuschagne et al., 2010; Bartz et al.…”
BackgroundResultInfluentialTabak, B. A., Meyer, M. L., Castle, E., Dutcher, J. M., Irwin, M. R., Han, J. H., Lieberman, M. D., & Eisenberger, N. I. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.006 · Cited by 67 · see citing works
“…of intranasal OT (Bartz et al., 2011; Macdonald, 2012), as well as associations between variation in oxytocin receptor gene polymorphisms (Tabak, 2013), the effects of AVP also appear to be moderated by similar factors (Rilling et al., 2012, 2014; Shalev et al., 2011; Thompson et al., 2006).”
BackgroundMethodResultInfluentialLinking Social Cognition to Learning and Memory
Leblanc, H., & Ramirez, S. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1280-20.2020 · Cited by 69 · see citing works
“, the amygdala) are ripe for future investigation (Markham and Juraska, 2002; Lebron-Milad et al., 2012; Rilling et al., 2014; Dumais and Veenema, 2016; Allsop et al., 2018).”
BackgroundThe endocrinology of human caregiving and its intergenerational transmission
Bos, P. A. (2016) · Development and Psychopathology · doi:10.1017/s0954579416000973 · Cited by 70 · see citing works
“…increases sensitivity to social stress (Ebstein et al., 2009) and aggressive facial responses to others (Thompson, George, Walton, Orr, & Benson, 2006), but also increased social cooperation (Brunnlieb et al., 2016; Rilling et al., 2014) and empathic concern for others (Tabak et al., 2015).”
BackgroundResultOxytocin reduces amygdala responses during threat approach
Radke, S., Volman, I., Kokal, I., Roelofs, K., de Bruijn, E. R. A., & Toni, I. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.02.028 · Cited by 67 · see citing works
“…after oxytocin administration, ales’ neural responses appear to become more similar to those f females receiving placebo and vice-versa (Rilling et al., 2014), hich might provide an explanatory framework for opposing mygdala responses between males and females in the placebo roups of…”
BackgroundSex- and context-dependent effects of oxytocin on social sharing
Ma, X., Zhao, W., Luo, R., Zhou, F., Geng, Y., Xu, L., Gao, Z., Zheng, X., Becker, B., & Kendrick, K. M. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.08.004 · Cited by 64 · see citing works
Oxytocin and sex differences in behavior
Caldwell, H. K. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.02.002 · Cited by 64 · see citing works
Oxytocin improves emotion recognition for older males
Campbell, A., Ruffman, T., Murray, J. E., & Glue, P. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.021 · Cited by 63 · see citing works
“Second, oxytocin increases functional connectivity in men but not women (Rilling et al., 2014).”
BackgroundRigney, N., Whylings, J., Mieda, M., de Vries, G. J., & Petrulis, A. (2019) · eNeuro · doi:10.1523/eneuro.0415-18.2019 · Cited by 63 · see citing works
Lukas, M., & Neumann, I. D. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.03.013 · Cited by 63 · see citing works
Improving the precision of intranasal oxytocin research
Winterton, A., Westlye, L. T., Steen, N. E., Andreassen, O. A., & Quintana, D. S. (2020) · Nature Human Behaviour · doi:10.1038/s41562-020-00996-4 · Cited by 62 · see citing works
Sparapani, S., Millet-Boureima, C., Oliver, J., Mu, K., Hadavi, P., Kalostian, T., Ali, N., Avelar, C. M., Bardies, M., Barrow, B., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9010089 · Cited by 63 · see citing works
“Brain fMRI during a Prisoner’s Dilemma Game revealed that, upon intranasal administration of 20 international units (IU) of AVP and compared to placebo, AVP increased BNST activity and reciprocated cooperation in men [255,299].”
BackgroundFrijling, J. L., van Zuiden, M., Koch, S. B. J., Nawijn, L., Veltman, D. J., & Olff, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.278 · Cited by 60 · see citing works
Ebert, A., & Brüne, M. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_21 · Cited by 62 · see citing works
Oxytocin and love: myths, metaphors and mysteries.
Carter, C. S. (2022) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100107 · Cited by 57 · see citing works
Nawijn, L., van Zuiden, M., Koch, S. B. J., Frijling, J. L., Veltman, D. J., & Olff, M. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.01.020 · Cited by 59 · see citing works
Kraaijenvanger, E. J., He, Y., Spencer, H., Smith, A. K., Bos, P. A., & Boks, M. P. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.016 · Cited by 57 · see citing works
Laursen, H. R., Siebner, H. R., Haren, T., Madsen, K., Grønlund, R., Hulme, O., & Henningsson, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00423 · Cited by 56 · see citing works
Opposing Oxytocin Effects on Intergroup Cooperative Behavior in Intuitive and Reflective Minds
Ma, Y., Liu, Y., Rand, D. G., Heatherton, T. F., & Han, S. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.87 · Cited by 55 · see citing works
Swaab, D. F., & Bao, A. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64123-6.00023-0 · Cited by 56 · see citing works
Daniëls, N., Moerkerke, M., Steyaert, J. G., Bamps, A., Debbaut, E., Prinsen, J., Tang, T., der Donck, S. V., Boets, B., & Alaerts, K. (2023) · Molecular Autism · doi:10.1186/s13229-023-00546-5 · Cited by 57 · see citing works
“Second, considering prior evidence of differential effects of oxytocin administration in men and women [21], we investigated treatment effect moderation depending on the biological sex of the participant.”
BackgroundSzymanska, M., Schneider, M., Chateau‐Smith, C., Nezelof, S., & Vulliez‐Coady, L. (2017) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12544 · Cited by 54 · see citing works
“In males, OT increased the activity of the caudate nucleus and left amygdala in response to reciprocated cooperation, and led to more rewarding cooperative interactions; whereas in women, OT either had no effect or decreased brain activity in those regions.(97) The administration of OT rendered male brain activity sim…”
BackgroundResultOxytocin Selectively Improves Empathic Accuracy: A Replication in Men and Novel Insights in Women
Bartz, J. A., Nitschke, J. P., Krol, S. A., & Tellier, P. (2019) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.01.014 · Cited by 55 · see citing works
Endogenous oxytocin, cortisol, and testosterone in response to group singing
Bowling, D. L., Gahr, J., Ancochea, P. G., Hoeschele, M., Canoine, V., Fusani, L., & Fitch, W. T. (2022) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.105105 · Cited by 51 · see citing works
“…differences remain “ very difficult ” to state (Caldwell, 2018), and evidence that oxytocin responses and reactions can be more pronounced in males is not unusual (Dumais et al., 2016; Feldman et al., 2010; Herzmann et al., 2013; Lynn et al., 2014; Rilling et al., 2014; Theodoridou et al., 2013).”
Schenk, L. A., Krimmel, S. R., & Colloca, L. (2017) · Pain · doi:10.1097/j.pain.0000000000000943 · Cited by 50 · see citing works
Rilling, J. K., Li, T., Chen, X., Gautam, P., Haroon, E., & Thompson, R. R. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00200 · Cited by 52 · see citing works
“Most studies have been done in men, where intranasal AVP has been found to facilitate cooperation (18, 19), enhance recognition of sexual cues (20), and enhance encoding of happy and angry faces (21).”
BackgroundSelf-citationFlattery, C. N. R., Ross, A. P., Sahu, S. P., Siegel, E. R., Dooyema, J. M., Cree, M. A., Stopa, E. G., Young, L. J., Rilling, J. K., Albers, H. E., et al. (2018) · American Journal of Primatology · doi:10.1002/ajp.22875 · Cited by 50 · see citing works
“AVP effects are also contextdependent, as it can promote pair-bonding behavior and cooperation (Brunnlieb et al., 2016; Rilling et al., 2014), but can also increase reactivity to threat and enhance anxiety (Morales-Medina, Witchey & Caldwell, 2016).”
BackgroundSelf-citationRole of oxytocin in the ventral tegmental area in social reinforcement
Borland, J. M., Grantham, K. N., Aiani, L. M., Frantz, K. J., & Albers, H. E. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.028 · Cited by 51 · see citing works
“Studies in humans also support a role for OT in regulating social behavior (Groppe et al., 2013; Rilling et al., 2014), and OT has been proposed as a potential treatment for a range of psychiatric disorders including autism spectrum disorder (Dichter et al.”
BackgroundWorsley, R., Santoro, N. F., Miller, K. K., Parish, S. J., & Davis, S. R. (2016) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2015.12.014 · Cited by 50 · see citing works
Rigney, N., Beaumont, R., & Petrulis, A. (2020) · Hormones and Behavior · doi:10.1016/j.yhbeh.2020.104715 · Cited by 47 · see citing works
“AVP, working through the vasopressin V1a receptor (V1aR), has been repeatedly implicated in modulation of social behaviors across vertebrate species, including humans, and often in a sex-different way (Choleris et al. 2009; Donaldson and Young 2008; Insel 2010; Duque-Wilckens et al. 2016; Guastella et al., 2010; Rilli…”
BackgroundResultNishina, K., Takagishi, H., Inoue‐Murayama, M., Takahashi, H., & Yamagishi, T. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137089 · Cited by 49 · see citing works
“[37] provide an alternative account of sex differences; they reported sex differences in neural activity following intranasal administration of oxytocin, and further stated that Table 1.”
BackgroundResultInfluentialSocial status strategy in early adolescent girls: Testosterone and value-based decision making
Cardoos, S. L., Suleiman, A. B., Johnson, M. M., van den Bos, W., Hinshaw, S. P., & Dahl, R. E. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.03.013 · Cited by 48 · see citing works
Oxytocin reduces neural activation in response to infant faces in nulliparous young women
Bos, P. A., Spencer, H., & Montoya, E. R. (2018) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsy080 · Cited by 47 · see citing works
Nishina, K., Takagishi, H., Takahashi, H., Sakagami, M., & Inoue‐Murayama, M. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00230 · Cited by 47 · see citing works
Shou, X., Xu, X., Zeng, X., Liu, Y., Yuan, H., Xing, Y., Jia, M., Wei, Q.-Y., Han, S., Zhang, R., et al. (2017) · Neuroscience Bulletin · doi:10.1007/s12264-017-0109-2 · Cited by 44 · see citing works
A neuroendocrine account of facial mimicry and its dynamic modulation
Kraaijenvanger, E. J., Hofman, D., & Bos, P. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.006 · Cited by 46 · see citing works
Neuropeptide Regulation of Social Attachment: The Prairie Vole Model
Tabbaa, M., Paedae, B., Liu, Y., & Wang, Z. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150055 · Cited by 53 · see citing works
Seeley, S. H., Chou, Y., & O'Connor, M. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.011 · Cited by 42 · see citing works
“Conversely, for female participants, IN-OT either had no significant effect or in fact decreased activation in those same regions (Rilling et al., 2014).”
Aita, C., Mizoguchi, Y., Yamamoto, M., SeguchI, Y., Yatsuga, C., Nishimura, T., Sugimoto, Y., Takahashi, D., Nishihara, R., Ueno, T., et al. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.12.139 · Cited by 44 · see citing works
Flanagan, J. C., Hand, A., Jarnecke, A. M., Maria, M. M. M., Brady, K. T., & Joseph, J. E. (2018) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000197 · Cited by 45 · see citing works
“…small sample size prevented us from explicitly examining sex differences in oxytocin response (Ditzen et al., 2013; Hoge et al., 2014; Lynn, Hoge, Fischer, Barrett, & Simon, 2014; Rilling et al., 2014), although the similar distribution by sex within groups partially mitigates this concern.”
Ma, X., Luo, L., Geng, Y., Zhao, W., Zhang, Q., & Kendrick, K. M. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00266 · Cited by 43 · see citing works
Rigney, N., Whylings, J., de Vries, G. J., & Petrulis, A. (2021) · Neuroendocrinology · doi:10.1159/000509421 · Cited by 42 · see citing works
The Effect of Oxytocin on Third-Party Altruistic Decisions in Unfair Situations: An fMRI Study
Hu, Y., Scheele, D., Becker, B., Voos, G., David, B., Hurlemann, R., & Weber, B. (2016) · Scientific Reports · doi:10.1038/srep20236 · Cited by 42 · see citing works
Oxytocin and Anxiety Disorders: Translational and Therapeutic Aspects
Naja, W., & Aoun, M. P. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0819-1 · Cited by 40 · see citing works
Flanagan, J. C., Allan, N. P., Calhoun, C. D., Badour, C. L., Maria, M. M. M., Brady, K. T., & Back, S. E. (2018) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000232 · Cited by 43 · see citing works
“Emerging literature indicates important sex differences in both neurobioloical and behavioral oxytocin outcomes (Ditzen et al., 2013; Flanagan et al., 2018; Hoge et al., 2014; MacDonald, 2015; Rilling et al., 2014; Yao et al., 2014).”
Skyt, I., Lunde, S. J., Baastrup, C., Svensson, P. J., Jensen, T. S., & Vase, L. (2019) · Pain · doi:10.1097/j.pain.0000000000001682 · Cited by 43 · see citing works
Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin
Jiang, X., Ma, X., Geng, Y., Zhao, Z., Zhou, F., Zhao, W., Yao, S., Yang, S., Zhao, Z., Becker, B., et al. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117668 · Cited by 39 · see citing works
Zhao, X., Mohammed, R., Tran, H., Erickson, M., & Kentner, A. C. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.03.018 · Cited by 43 · see citing works
A human tendency to anthropomorphize is enhanced by oxytocin
Scheele, D., Schwering, C., Elison, J. T., Spunt, R., Maier, W., & Hurlemann, R. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.05.009 · Cited by 41 · see citing works
Positive reinforcing effect of oxytocin microinjection in the rat central nucleus of amygdala
László, K., Kovács, A., Zagorácz, O., Ollmann, T., Péczely, L., Kertes, E., Lacy, D. G., & Lénárd, L. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.09.021 · Cited by 43 · see citing works
An integrated framework for the role of oxytocin in multistage social decision‐making
Piva, M., & Chang, S. W. C. (2018) · American Journal of Primatology · doi:10.1002/ajp.22735 · Cited by 38 · see citing works
“…as a line of research ultimately including a sample size of over 300 participants determined that OT increases activation in the ventral striatum inmen but decreases activation in the same region in women during the canonical prisoner's dilemma game (Feng et al., 2015; Rilling et al., 2012, 2014).”
BackgroundA precision medicine approach to oxytocin trials
Andari, E., Hurlemann, R., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_29 · Cited by 40 · see citing works
- Authors
- Rilling, J. K., DeMarco, A. C., Hackett, P. D., Chen, X., Gautam, P., Stair, S., Haroon, E., Thompson, R., Ditzen, B., Patel, R., & Pagnoni, G.
- Affiliations
- Emory University (US)
- University of Kansas (US)
- Bowdoin College (US)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Rilling, James K.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 39
- Pages
- 237-248
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3842401
- OpenAlex
- W2129575907
- Cited by
- 343
- References
- 54
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 13 · 2023: 16 · 2022: 19 · 2021: 38 · 2020: 35 · 2019: 50 · 2018: 35 · 2017: 35 · 2016: 32 · 2015: 28 · 2014: 17
- FWCI
- 38.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (R01 MH084068-01A1)
- National Center for Research Resources
- Yerkes Regional Primate Research Center (2P51RR000165-51)
- National Institutes of Health
- Presbyterian Historical Society (UL1 RR025008)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin, vasopressin, sex differences, intranasal administration, social interaction, prisoner's dilemma game, cooperation, conciliation, social bonding, reward processing, brain activity, nonapeptide, mental illness
- MeSH terms
- Administration, Intranasal, Adolescent, Arginine Vasopressin, Brain, Cooperative Behavior, Double-Blind Method, Female, Game Theory, Humans, Image Processing, Computer-Assisted, Interpersonal Relations, Magnetic Resonance Imaging, Male, Oxytocin, Sex Characteristics, Social Behavior, Young Adult, Functional Neuroimaging
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