Effects of intranasal oxytocin on emotional face processing in women
Open accessAbstract
The neuropeptide oxytocin (OXT) has previously been found to reduce amygdala reactivity to social and emotional stimuli in healthy men. The present study aimed to investigate the effect of intranasally administered OXT on brain activity in response to social emotional stimuli of varying valence in women. In a functional magnetic-resonance imaging study, sixteen women were presented with fearful, angry, happy and neutral facial expressions after a single dose of 24IU OXT or a placebo administration in a within-subject design. Group analysis revealed that the blood-oxygen-level-dependent (BOLD) signal was enhanced in the left amygdala, the fusiform gyrus and the superior temporal gyrus in response to fearful faces and in the inferior frontal gyrus in response to angry and happy faces following OXT treatment. This effect was independent of fixation pattern to specific sections of the facial stimuli as revealed by eye tracking and independent of basal plasma levels of OXT, estradiol, and progesterone. The results are at odds with the previously reported effects found in men. Future studies should include both sexes to determine a possible sexual dimorphism in the neural effects of OXT, considering gonadal steroids and OXT receptor affinity.
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Task-based fMRI has often shown opposite findings in males and females, namely in amygdala activation.
“task-based fMRI has often shown opposite findings in males and females namely in terms of amygdala activation.14, 15”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [14]
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 [14]
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 [14]
Oxytocin lowers amygdala activity in response to fear in men but raises amygdala activity to similar stimuli in women.
“while it has been demonstrated that OXT decreases amygdala activity in response to fear in men (Kirsch et al., 2005), it appears to increase amygdala activity to similar stimuli in women (Domes et al., 2010).”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Domes et al., 2010
Separate oxytocin-application studies in humans indicate that there may be differential amygdala reactivity to fearful faces and fearful/threatening scenes in men and women.
“separate OXT-application studies in humans have indicated that there may be differential amygdala reactivity to fearful faces and fearful/threatening scenes in men (14, 15) and women (16, 17).”
From Oxytocin, the peptide that bonds the sexes also divides them (2016) · cites this paper as [16]
Previous studies indicate that oxytocin may induce sex-dependent changes in amygdala activation to emotional stimuli, but in opposite directions to the present findings.
“Previous studies on amygdala responses to fearful faces and fearful/threatening scenes (14 -17, 30) and social risk (31) have also indicated that OXT may induce sex-dependent changes in amygdala activation to emotional stimuli.”
From Oxytocin, the peptide that bonds the sexes also divides them (2016) · cites this paper as [16]
In healthy subjects, intranasal oxytocin alters pro-social feelings, social communication, emotional recognition, self-perception, and social interactions with offspring.
“Generally, in healthy subjects pro-social feelings, including generosity and trust (6–8), social communication and emotional recognition (9,10), self-perception (11), and social interactions with offspring are altered by OT(12).”
From Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles (2013) · cites this paper as [9]
The sample was restricted to males and may not generalize to females.
“our sample was restricted to males, given the role of sex hormones on OXT neural effect's (Domes et al, 2010), and may not generalize to females.”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Domes et al, 2010
Intranasal OT increases amygdala reactivity in women.
“but increases it in women (11, 12).”
From Oxytocin receptors in the anteromedial bed nucleus of the stria terminalis promote stress-induced social avoidance in female California mice (2018) · cites this paper as [11]
Oxytocin has been shown to have differential effects on emotional responding in males and females.
“Second, OXT has been shown to have differential effects on emotional responding in males and females (Domes et al, 2010).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Domes et al, 2010
In human participants, BOLD signals in the amygdala in women, unlike in men, increase when viewing fearful faces.
“Interestingly, one study on human participants found that the BOLD signals in the amygdala in women, unlike in men, actually increase when viewing fearful faces (Domes et al., 2010).”
From Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology (2014) · cites this paper as Domes et al., 2010
Previous studies have shown differential effects of OT on male and female participants.
“Moreover, previous studies have shown differential effects of OT on male and female participants (e.g.Domes et al., 2010;Feldman et al., 2010).”
From OT promotes closer interpersonal distance among highly empathic individuals (2015) · cites this paper as Domes et al., 2010
The study cannot exclude the possibility that not standardizing menstrual cycle phase may have influenced the results.
“We cannot exclude the possibility that this may have influenced our results, although similar effects of OT on amygdala reactivity previously were found in females tested in the follicular phase (Domes et al, 2010) and luteal phase (Bertsch et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Domes et al, 2010
OT increases reactivity in the amygdala during the processing of fearful faces in females.
“even to increase reactivity in the amygdala during the processing of fearful faces in females [19].”
From A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli (2013) · cites this paper as [19]
Recent experimental evidence points to sex-dimorphic effects of OT nasal spray in humans.
“is in agreement with recent experimental evidence pointing to the sex-dimorphic effects of OT nasal spray in humans [19], [45] [56], [57].”
From A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli (2013) · cites this paper as [19]
There is evidence that male and female subjects respond differently to oxytocin.
“Third, our study used only male subjects, and there is evidence that male and female subjects respond differently to oxytocin (Domes et al., 2010).”
From Oxytocin decreases aversion to angry faces in an associative learning task (2010) · cites this paper as Domes et al., 2010
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Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?
McCullough, M. E., Churchland, P. S., & Mendez, A. J. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.018 · Cited by 416 · see citing works
Is oxytocin “nature’s medicine”
Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394 · see citing works
“The consequences of treatment with exogenous peptides can vary by sex in humans (Thompson et al., 2006; Domes et al., 2010; Taylor et al., 2010), nonhuman primates (Jiang and Platt, 2018), and other mammals (De Vries and Panzica, 2006; Carter, 2007; Albers, 2015; Okhovat et al.”
BackgroundBakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.34 · Cited by 383 · see citing works
Riem, M. M. E., Bakermans-Kranenburg, M. J., Pieper, S., Tops, M., Boksem, M. A. S., Vermeiren, R. R. J. M., van IJzendoorn, M. H., & Rombouts, S. A. R. B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.006 · Cited by 366 · see citing works
The amygdala as a hub in brain networks that support social life
Bickart, K. C., Dickerson, B. C., & Feldman Barrett, L. (2014) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2014.08.013 · Cited by 344 · see citing works
“For example, OXT-related changes in amygdala activity might depend in part on gender (Domes et al., 2010), suggesting there is still much to learn about the conditions that determine the direction of OXT's effect on the amygdala.”
BackgroundVan IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.008 · Cited by 365 · see citing works
Rilling, J. K., DeMarco, A. C., Hackett, P. D., Chen, X., Gautam, P., Stair, S., Haroon, E., Thompson, R., Ditzen, B., Patel, R., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.022 · Cited by 343 · 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).”
BackgroundA review of safety, side-effects and subjective reactions to intranasal oxytocin in human research
MacDonald, E., Dadds, M. R., Brennan, J. L., Williams, K., Levy, F., & Cauchi, A. J. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.02.015 · Cited by 352 · see citing works
“HR; self report & obs Domes et al. (2007b) 30 M 30 M 24 IU single Syntocinon Novartis All ingredients minus OT.”
Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin
Szeto, A., McCabe, P. M., Nation, D. A., Tabak, B. A., Rossetti, M. A., McCullough, M. E., Schneiderman, N., & Mendez, A. J. (2011) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31821df0c2 · Cited by 330 · see citing works
van Anders, S. M., Goldey, K. L., & Kuo, P. X. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.06.001 · Cited by 321 · see citing works
“On one hand, there is evidence for gender/sex-specific effects (Carter, 2007; Taylor et al., 2010; Domes et al., 2010), which validates this approach.”
Oxytocin improves specific recognition of positive facial expressions
Marsh, A. A., Yu, H. H., Pine, D. S., & Blair, R. J. R. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1780-4 · Cited by 321 · see citing works
“Rodent studies suggest that oxytocin’ se ffects are enhanced by interaction with estrogens (Champagne et al. 2001 ;M cCarthy et al.1996), and recent neuroimaging studies in humans suggest that oxytocin enhances activity in neural regions involved in processing emotional facial expressions in women but reduces activity…”
BackgroundRilling, 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
“Domes et al. (2010) reported a 34.2 pg/ ml increase at 45 min post-administration, whereas Andari et al. (2010) reported a 1.6 pg/ml increase 10 min postadministration.”
InfluentialBethlehem, R. A. I., van Honk, J., Auyeung, B., & Baron-Cohen, S. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.10.011 · Cited by 285 · see citing works
“The fact that there is a sex difference in amygdala activity in relation to OT and fearful faces (Domes et al., 2010) and that different sub-regions of the amygdala respond differently to OTadministration (Gamer et al.”
BackgroundInfluentialProsocial 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 · see citing works
“2010 [46] 16 F 24 IU”
The contributions of oxytocin and vasopressin pathway genes to human behavior
Ebstein, R. P., Knafo, A., Mankuta, D., Chew, S. H., & Lai, P. S. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.014 · Cited by 283 · see citing works
Immunohistochemical localization of oxytocin receptors in human brain
Boccia, M. L., Petrusz, P., Suzuki, K., Marson, L., & Pedersen, C. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.048 · Cited by 276 · see citing works
The animal and human neuroendocrinology of social cognition, motivation and behavior
McCall, C., & Singer, T. (2012) · Nature Neuroscience · doi:10.1038/nn.3084 · Cited by 273 · see citing works
Bales, K. L., Perkeybile, A. M., Conley, O. G., Lee, M. H., Guoynes, C. D., Downing, G. M., Yun, C. R., Solomon, M., Jacob, S., & Mendoza, S. P. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.08.025 · Cited by 265 · see citing works
“Generally, in healthy subjects, prosocial feelings, including generosity and trust (6–8), social communication and emotional recognition (9,10), self-perception (11), and social interactions with offspring are altered by OT (12).”
Quintana, D. S., Lischke, A., Grace, S., Scheele, D., Ma, Y., & Becker, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00864-7 · Cited by 263 · see citing works
Self-citationOxytocin facilitates protective responses to aversive social stimuli in males
Striepens, N., Scheele, D., Kendrick, K. M., Becker, B., Schäfer, L., Schwalba, K., Reul, J., Maier, W., & Hurlemann, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208852109 · Cited by 242 · see citing works
“First, our study included only men and, against the background that previous studies reported sex-specific effects of OXT (26, 27), we cannot extrapolate our findings to women.”
ResultEffects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder
Domes, G., Heinrichs, M., Kumbier, E., Grossmann, A., Hauenstein, K., & Herpertz, S. C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.007 · Cited by 255 · see citing works
Self-citationAuyeung, B., Lombardo, M. V., Heinrichs, M., Chakrabarti, B., Sule, A., Deakin, J. B., Bethlehem, R. A. I., Dickens, L., Mooney, N., Sipple, J. A. N., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.146 · Cited by 234 · see citing works
Self-citationNonapeptide 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 · see citing works
Kinetics 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).”
BackgroundSelf-citationThe evolutionary psychology of women's aggression
Campbell, A. C. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0078 · Cited by 235 · see citing works
Chen, F. S., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R. P., & Heinrichs, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113079108 · Cited by 268 · see citing works
“Because previous results have suggested sex differences in the effects of social support on the stress response (12, 57), as well as sex differences in associations between OXTR genotype and phenotype (49) and responses to intranasal oxytocin administration (26, 58), we decided to limit the present initial study to ma…”
ResultSelf-citationLischke, A., Berger, C., Prehn, K., Heinrichs, M., Herpertz, S. C., & Domes, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.015 · Cited by 221 · see citing works
“Future study could explicitly investigate the sexual dimorphism of OT effects in the central nervous system as suggested by previous studies (Carter, 2007; Domes et al., 2010).”
MethodGroppe, S. E., Gossen, A., Rademacher, L., Hahn, A., Westphal, L., Gründer, G., & Spreckelmeyer, K. N. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.023 · Cited by 218 · see citing works
“Although discordant with studies in male participants suggesting that oxytocin reduces arousal in response to threatening social stimuli [(5,10,11) but see (44) for an alternative account], our finding is well in line with a recent study suggesting enhanced arousal toward threatening social cues under oxytocin in null…”
BackgroundResultBaribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 229 · see citing works
“(Kirsch et al., 2005). they detected a pattern somewhat opposite to that observed in males, with increased amygdala activity while observing negative facial expression in response to oxytocin treatment (Domes et al., 2010).”
BackgroundResultInfluentialPuglia, M. H., Lillard, T. S., Morris, J. P., & Connelly, J. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422096112 · Cited by 216 · see citing works
The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies
Modi, M. E., & Young, L. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.010 · Cited by 218 · see citing works
“Intranasal OT increases the perception of socially important information, like emotion recognition (Domes et al., 2010), empathic perception (Bartz et al., 2010), facial identity (Rimmele et al., 2009) and the response to biological motion (Keri and Benedek, 2009), see (Bos et al., 2011) for a…”
BackgroundGenetic origins of social networks in rhesus macaques
Brent, L. J. N., Heilbronner, S. R., Horvath, J. E., Gonzalez-Martinez, J., Ruiz-Lambides, A., Robinson, A. G., Skene, J. H. P., & Platt, M. L. (2013) · Scientific Reports · doi:10.1038/srep01042 · Cited by 220 · see citing works
Prenatal and postnatal hormone effects on the human brain and cognition
Bonnie Auyeung, B., Lombardo, M. V., & Baron‐Cohen, S. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1268-2 · Cited by 219 · see citing works
“fMRI studies have shown that oxytocin exerts influence on important neural circuits for a wide range of social–cognitive abilities such as eye gaze, mentalizing, emotion recognition, and learning [18, 46, 47, 57, 83, 89, 110, 117].”
BackgroundBertsch, K., Gamer, M., Schmidt, B., Schmidinger, I., Walther, S., Kästel, T., Schnell, K., Büchel, C., Domes, G., & Herpertz, S. C. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13020263 · Cited by 214 · see citing works
Self-citationDodhia, S., Hosanagar, A., Fitzgerald, D. A., Labuschagne, I., Wood, A. G., Nathan, P. J., & Phan, K. L. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.53 · Cited by 209 · see citing works
Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex
Sripada, C. S., Phan, K. L., Labuschagne, I., Welsh, R., Nathan, P. J., & Wood, A. G. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000533 · Cited by 197 · see citing works
Paloyelis, Y., Doyle, O. M., Zelaya, F. O., Maltezos, S., Williams, S. C., Fotopoulou, A., & Howard, M. A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.005 · Cited by 187 · see citing works
“Biological P IN-OT on amygdala functional connectivity (105) or amygdala response involving left (92,98,113,114) or right amygdala laterality (97,100,101).”
Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience
Kumsta, R., Hummel, E., Chen, F. S., & Heinrichs, M. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00083 · Cited by 207 · see citing works
Self-citationOxytocin, the peptide that bonds the sexes also divides them
Gao, S., Becker, B., Luo, L., Geng, Y., Zhao, W., Yin, Y., Hu, J., Gao, Z., Gong, Q., Hurlemann, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602620113 · Cited by 186 · see citing works
“The amygdala has a sexually dimorphic distribution and expression of OXT receptors in nonprimate mammals (12, 13), and separate OXT-application studies in humans have indicated that there may be differential amygdala reactivity to fearful faces and fearful/threatening scenes in men (14, 15) and women (16, 17).”
BackgroundDumais, K. M., Bredewold, R., Mayer, T. E., & Veenema, A. H. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.08.012 · Cited by 201 · see citing works
Oxytocin increases amygdala reactivity to threatening scenes in females
Lischke, A., Gamer, M., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., Herpertz, S. C., & Domes, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.011 · Cited by 194 · see citing works
“Sex-specific differences in amygdala reactivity to threatrelated scenes have previously been reported (Domes et al., 2010b; Mackiewicz et al., 2006), indicating that threat-processing is generally enhanced in females.”
BackgroundMethodResultInfluentialSelf-citationIntranasal oxytocin blocks alcohol withdrawal in human subjects
Pedersen, C. A., Smedley, K. L., Leserman, J., Jarskog, L. F., Rau, S. W., Kampov‐Polevoi, A., Casey, R. L., Fender, T., & Garbutt, J. C. (2013) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01958.x · Cited by 196 · see citing works
“…dose) intranasal OT treatment, which appears to result in penetration of a significant amount of the neuropeptide into the brain (Born et al., 2002; Domes et al., 2007a, 2010; Kirsch et al., 2005), increases interpersonal trust and cooperation, improves social cognition, and reduces anxiety…”
Brain oxytocin: how puzzle stones from animal studies translate into psychiatry
Grinevich, V., & Neumann, I. D. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0802-9 · Cited by 189 · see citing works
Walker, S. C., Trotter, P. D., Swaney, W. T., Marshall, A. G., & McGlone, F. P. (2017) · Neuropeptides · doi:10.1016/j.npep.2017.01.001 · Cited by 193 · see citing works
“A range of studies in humans have shown that intranasal inhalation of oxytocin increases attention to and accuracy in discriminating visual social cues such as emotional facial expressions (Domes et al., 2013, 2010, 2007b).”
BackgroundOxytocin enhances inter-brain synchrony during social coordination in male adults
Mu, Y., Guo, C., & Han, S. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw106 · Cited by 177 · see citing works
“Because previous studies have shown evidence for distinct OT effects on neural underpinnings of social 115 cognitive/affective processes in male and female participants (Kirsch et al., 2005; Domes et al., 2010; Ditzen et al., 2012), future research should integrate EEG recording and intranasal administration of OT to…”
BackgroundResultThe effect of intranasal administration of oxytocin on fear recognition
Fischer-Shofty, M., Shamay-Tsoory, S. G., Harari, H., & Levkovitz, Y. (2010) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.09.003 · Cited by 184 · see citing works
Duque-Wilckens, N., Steinman, M. Q., Busnelli, M., Chini, B., Yokoyama, S., Pham, M., Laredo, S. A., Hao, R., Perkeybile, A. M., Minie, V. A., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.024 · Cited by 181 · see citing works
“Intranasal OT reduces amygdala reactivity in men (5,7) but increases it in women (11,12).”
BackgroundSocial attention: a possible early indicator of efficacy in autism clinical trials
Dawson, G., Bernier, R., & Ring, R. H. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-11 · Cited by 181 · see citing works
“In healthy human volunteers, a broad range of effects have been described for OT administration on social cognition, including improvements in the encoding and recognition of facial expression [74], increased empathic perception [75,76], enhanced memory encoding of faces in humans, but not of non-social stimuli [77] a…”
BackgroundOxytocin increases recognition of masked emotional faces
Schulze, L., Lischke, A., Greif, J., Herpertz, S. C., Heinrichs, M., & Domes, G. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.011 · Cited by 180 · see citing works
“In addition, recent results suggest gender-specific modulatory effects of oxytocin (Domes et al., 2010).”
Self-citationMacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181 · see citing works
“…regards to clinical studies of the effects of IN OT, a sex difference in its effects has been demonstrated in some singledose studies (Hurlemann et al., 2010), including studies of OT’s effects on the amygdala (Domes et al., 2010; Rupp et al., 2012), and interpersonal behavior (Liu et al., 2012).”
BackgroundWigton, R., Radua, J., Allen, P., Averbeck, B., Meyer-Lindenberg, A., McGuire, P., Shergill, S. S., & Fusar-Poli, P. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130289 · Cited by 179 · see citing works
Rosenfeld, A. J., Lieberman, J. A., & Jarskog, L. F. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbq015 · Cited by 178 · see citing works
Human neuroimaging of oxytocin and vasopressin in social cognition
Zink, C. F., & Meyer-Lindenberg, A. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.01.016 · Cited by 176 · see citing works
“, 2007a), in females, oxytocin enhanced activity in the temporal poles, as well as superior temporal gyrus, fusiform gyrus, and insula (Domes et al., 2010), brain areas highly involved with face perception and emotion encoding (Haxby et al.”
BackgroundInfluentialIntranasal administration of oxytocin: behavioral and clinical effects, a review
Veening, J. G., & Olivier, B. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.012 · Cited by 169 · see citing works
“…al., 2012; Opar, 2008; Parker et al., 2005; immele et al., 2009; Savaskan et al., 2008; Shamay-Tsoory et al., 009; Smith et al., 2012; Theodoridou et al., 2009) leading to otential treatment of autistic symptoms (Domes et al., 2010; eyer-Lindenberg, 2008; Meyer-Lindenberg et al., 2011; Opar, 008).”
BackgroundMethodInfluentialThe Resilience handbook: approaches to stress and trauma
(2014) · Choice Reviews Online · doi:10.5860/choice.51-5313 · Cited by 161 · see citing works
Domes, G., Kumbier, E., Heinrichs, M., & Herpertz, S. C. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.254 · Cited by 160 · see citing works
Self-citationNeural mechanisms of social decision-making in the primate amygdala
Chang, S. W. C., Fagan, N. A., Toda, K., Utevsky, A. V., Pearson, J. M., & Platt, M. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514761112 · 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
Roles of Oxytocin in Stress Responses, Allostasis and Resilience
Takayanagi, Y., & Onaka, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010150 · Cited by 164 · see citing works
Quintana, D. S., Alvares, G. A., Hickie, I. B., & Guastella, A. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.011 · Cited by 149 · see citing works
Yamasue, H., Yee, J. R., Hurlemann, R., Rilling, J. K., Chen, F. S., Meyer-Lindenberg, A., & Tost, H. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3327-12.2012 · Cited by 149 · see citing works
“…a decreased response in the inferior occipital gyrus during the recognition of fearful facial expressions, an area crucial for the processing of visual emotional stimuli that has been shown to be directly modulated by OT in a previous pharmacological challenge study (Domes et al., 2010).”
BackgroundInfluentialLow CSF oxytocin reflects high intent in suicide attempters
Jokinen, J., Chatzittofis, A., Hellström, C., Nordström, P., Uvnäs-Moberg, K., & Åsberg, M. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.016 · Cited by 143 · see citing works
“Since some studies of both the oxytocin system and suicidal behaviour have shown gender differences (Hawton, 2000; Domes et al., 2010), we also assessed men and women separately.”
BackgroundMDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions
Hysek, C. M., Domes, G., & Liechti, M. E. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2645-9 · Cited by 144 · see citing works
Self-citationBredewold, R., & Veenema, A. H. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.011 · Cited by 144 · see citing works
“Furthermore, intranasal OXT decreased fear and threat-induced amygdala blood oxygen level-dependent (BOLD) activation in men, but increased it in women [44,45 ,46,47] (Figure 2b).”
BackgroundEffects of MDMA and intranasal oxytocin on social and emotional processing
Kirkpatrick, M. G., Lee, R., Wardle, M. C., Jacob, S., & de Wit, H. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.12 · Cited by 143 · see citing works
Emotion recognition and oxytocin in patients with schizophrenia
Averbeck, B. B., Bobin, T., Evans, S., & Shergill, S. S. (2011) · Psychological Medicine · doi:10.1017/s0033291711001413 · Cited by 144 · see citing works
“This is an important limitation that should be examined in future studies as it has been shown that oxytocin affects processing of emotional faces differently in males and females (Domes et al. 2010).”
BackgroundOxytocin Modulates Neural Reactivity to Children's Faces as a Function of Social Salience
Wittfoth-Schardt, D., Gründing, J., Wittfoth, M., Lanfermann, H., Heinrichs, M., Domes, G., Buchheim, A., Gündel, H., & Waller, C. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.47 · Cited by 139 · see citing works
“Thirty minutes before scanning, 24 IU of OT (Syntocinon; Novartis, Basel, Switzerland) or PL (ingredients equivalent except for the peptide) were intranasally administered in three puffs per nostril with 4 IU each (Bartz et al, 2011; Born et al, 2002; Domes et al, 2007, 2009).”
MethodSelf-citationGordon, J. L., Rubinow, D. R., Eisenlohr-Moul, T. A., Leserman, J., & Girdler, S. S. (2015) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000528 · Cited by 147 · see citing works
Harari-Dahan, O., & Bernstein, A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.007 · Cited by 135 · see citing works
Herpertz, S. C., & Bertsch, K. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020216 · Cited by 139 · see citing works
Self-citationFan, Y., Herrera-Meléndez, A. L., Pestke, K., Feeser, M., Aust, S., Otte, C., Pruessner, J. C., Böker, H., Bajbouj, M., & Grimm, S. (2014) · Human Brain Mapping · doi:10.1002/hbm.22553 · Cited by 134 · see citing works
“Gender specific OXT effect has been previously reported on stress reactivity and emotional processing [Ditzen et al., 2013; Domes et al., 2010].”
BackgroundOxytocin facilitates accurate perception of competition in men and kinship in women
Fischer-Shofty, M., Levkovitz, Y., & Shamay-Tsoory, S. G. (2013) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsr100 · Cited by 132 · see citing works
Gorka, S. M., Fitzgerald, D. A., Labuschagne, I., Hosanagar, A., Wood, A. G., Nathan, P. J., & Phan, K. L. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.168 · Cited by 131 · see citing works
“Second, our sample was restricted to males, given the role of sex hormones on OXT neural effect’s (Domes et al, 2010), and may not generalize to females.”
BackgroundSex-specific effects of stress on oxytocin neurons correspond with responses to intranasal oxytocin
Steinman, M. Q., Duque-Wilckens, N., Greenberg, G. D., Hao, R., Campi, K. L., Laredo, S. A., Laman-Maharg, A., Manning, C. E., Doig, I. E., Lopez, E. M., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.007 · Cited by 131 · see citing works
“In one study, intranasal OT enhanced blood oxygen level–dependent responses of the amygdala during an aversive social context in women but reduced this response in men (21).”
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
“By contrast, IN-OT may increase the capacity to regulate negative affect by increasing activity in the medial prefrontal cortex (mPFC [19,48,49]), ventral lateral prefrontal cortex (vlPFC [13,48,50,52,70]), and dorsal lPFC [49,70], which comprise the neural circuits for automatic and effortful regulation of emotion [6…”
BackgroundResultInfluentialBonding after trauma: on the role of social support and the oxytocin system in traumatic stress
Olff, M. (2012) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v3i0.18597 · Cited by 131 · see citing works
“Also, although oxytocin seems to facilitate a positive psychobiological stress response for both men and women, some studies indicate different responses in women (Domes et al., 2010; Kubzansky et al., 2012; Lischke et al., 2012).”
Intranasal oxytocin increases covert attention to positive social cues
Domes, G., Sibold, M., Schulze, L., Lischke, A., Herpertz, S. C., & Heinrichs, M. (2013) · Psychological Medicine · doi:10.1017/s0033291712002565 · Cited by 130 · see citing works
“An exclusively male sample was investigated because of empirical evidence suggesting sex differences in responding to intranasal OT (Domes et al. 2010 ; Lischke et al. 2012b).”
BackgroundResultSelf-citationAerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
Modi, M. E., Connor-Stroud, F., Landgraf, R., Young, L. J., & Parr, L. A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.011 · Cited by 129 · see citing works
“These studies report numerous effects of IN-OT on human social cognition, including enhanced eye gaze, increased trust, better recognition of facial emotions, improved face memory, and empathy (Domes et al., 2010; Guastella and MacLeod, 2012; Guastella et al., 2008; Kosfeld et al., 2005; Rimmele et al., 2009; Savaskan…”
Sex differences in fear extinction
Velasco, E. R., Florido, A., Milad, M. R., & Andero, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.020 · Cited by 125 · see citing works
The effects of oxytocin on social cognition and behaviour in frontotemporal dementia
Jesso, S., Morlog, D., Ross, S., Pell, M. D., Pasternak, S., Mitchell, D. G. V., KERTESZ, A. E., & Finger, E. C. (2011) · Brain · doi:10.1093/brain/awr171 · Cited by 129 · see citing works
“…in healthy adults may be mediated via oxytocin-induced reductions in amygdala activation during threatening and fearful stimuli (Kirsch et al., 2005; Domes et al., 2007a; Labuschagne et al., 2010); however, in females, oxytocin may increase amygdala activity to fearful faces (Domes et al., 2010).”
BackgroundAutism and Oxytocin: New Developments in Translational Approaches to Therapeutics
Green, J. J., & Hollander, E. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.006 · Cited by 124 · see citing works
Schmid, M., Petermann, F., & Fegert, J. M. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-3 · Cited by 124 · see citing works
“This was particularly evident in studies with adult borderline patients [26-28].”
BackgroundShamay-Tsoory, S. G., Abu-Akel, A., Palgi, S., Sulieman, R., Fischer-Shofty, M., Levkovitz, Y., & Decety, J. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.015 · Cited by 123 · see citing works
“Dosage and waiting time corresponded to those previously used in experiments designed to investigate the effect of the intranasal administration of OT on behavior in humans (Kirsch et al., 2005; Kosfeld et al., 2005; Domes et al., 2010; Guastella et al., 2010).”
MethodKoch, S. B. J., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.11.018 · Cited by 123 · see citing works
Grace, 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
Self-citation
- Authors
- Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C.
- Affiliations
- University of Freiburg (DE)
- University of Rostock (DE)
- Universitätsmedizin Rostock (DE)
- Heidelberg University (DE)
- Corresponding author
- Domes, Gregor
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 35
- Issue
- 1
- Pages
- 83-93
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2038181972
- Cited by
- 521
- References
- 58
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 14 · 2023: 18 · 2022: 13 · 2021: 27 · 2020: 21 · 2019: 25 · 2018: 29 · 2017: 45 · 2016: 41 · 2015: 45 · 2014: 53 · 2013: 64 · 2012: 44
- FWCI
- 44.39
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Bundesministerium für Bildung und Forschung (01GW0784)
- Universität Zürich
- Deutsche Forschungsgemeinschaft (Do1312/1-1)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP001-114788)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin, intranasal administration, emotional face processing, amygdala, sexual dimorphism, women, facial expressions, fusiform gyrus, superior temporal gyrus, inferior frontal gyrus, estradiol, progesterone, sex steroids, BOLD signal
- MeSH terms
- Administration, Intranasal, Adult, Anger, Emotions, Estradiol, Eye Movements, Facial Expression, Fear, Female, Hormones, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Oxytocin, Photic Stimulation, Progesterone, Social Perception, Young Adult
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