The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index; none of the 38 sources its claims cite is checked for support yet.
Oxytocin, the peptide that bonds the sexes also divides them
Open accessAbstract
Significance: To interpret and respond appropriately to social cues is a fundamental aspect of human nature that becomes impaired in many mental disorders. The past decade has witnessed unprecedented excitement across neuroscience, psychology, and psychiatry regarding the role of oxytocin in human social cognition and its potential therapeutic use. There is also a considerable long-established public interest in behavioral sex differences and the molecular and brain mechanisms responsible. The current findings provide the first mechanistic explanation, to our knowledge, for how this key social molecule has evolved sex-dependent actions on amygdala function to influence the salience and attractiveness of positive social attributes in women but negative ones in men.
Overview
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Written from the paper’s full text.
TL;DR
Intranasal oxytocin produced sex- and valence-dependent changes in amygdala responses during social impression formation: it enhanced left amygdala reactivity to people who praised others in women but to people who criticized others in men. These neural effects were accompanied by opposite likeability effects, with oxytocin increasing women’s overall likeability ratings and tending to decrease men’s.
Key findings
- In a whole-brain mixed-effect ANOVA, a significant treatment × sex interaction occurred in the left amygdala for social criticism vs. praise (k = 262, P_FWE = 0.001). Oxytocin enhanced left amygdala responses to criticizing vs. praising others in males (t35 = 3.1, P = 0.004, d = 1.02) but attenuated them in females (t35 = −3.18, P = 0.003, d = 1.09).
- Separate extraction showed greater amygdala reactivity in men to those who criticized others (t35 = 3.22, P = 0.003, d = 1.04) and in women to those who praised them (t35 = 2.45, P = 0.019, d = 0.82). No such effect was found for the parallel object-directed condition.
- Oxytocin altered left amygdala–right insula functional connectivity in a treatment × sex interaction (t70 = 4.19, P_FWE = 0.009): it increased coupling in males (t35 = 3.59, P = 0.001, d = 1.18) but reduced it in females (t35 = −2.29, P = 0.03, d = 0.76) for criticizing vs. praising others. Connectivity for criticizing people in males and praising people in females was associated with likeability ratings after controlling for anxiety and mood (OXT males criticizing: r = 0.62, P = 0.02; OXT females praising: r = 0.5, P = 0.04).
- Likeability ratings showed main effects of valence (F2,140 = 213.51, P < 0.001, η²P = 0.75) and target (F1,70 = 35.83, P < 0.001, η²P = 0.34); faces paired with criticism were rated lowest (3.83 ± 0.1) and praise highest (6 ± 0.09). A treatment × sex interaction (F1,70 = 7.08, P = 0.01, η²P = 0.09) showed oxytocin increased females’ overall likeability ratings (F1,70 = 4.25, P = 0.04, η²P = 0.06) and tended to decrease males’ (F1,70 = 2.89, P = 0.09, η²P = 0.04).
Methods
- Double-blind, placebo-controlled, between-subject design: 80 healthy right-handed volunteers (age 19–27 y; M ± SD, 22.8 ± 1.7 y) were recruited; data from 6 were lost, leaving 37 females (OXT n = 21) and 37 males (OXT n = 18) in final analyses. Participants self-administered intranasal oxytocin (24 IU) or placebo and underwent fMRI after 45 min.
- During fMRI, participants completed a first-impression task in which neutral faces were paired with statements describing criticizing or praising people or nonsocial objects; faces were later presented alone and rated for likeability.
- fMRI data were analyzed with SPM8/DPARSF using a whole-brain mixed-effect ANOVA with treatment and sex as between-subject factors and valence as a within-subject factor, plus generalized psychophysiological interaction (gPPI) functional connectivity analysis focused on amygdala coupling with salience-network regions.
Limitations
- The paper does not include a dedicated limitations section. It notes that sex-dependent salience effects of oxytocin may be influenced by emotional experience and contextual factors, citing a trauma study, and that the observed effects were social-specific, with no object-directed or face-alone effects.
- Evident from the text: the final sample was 74 healthy, right-handed young adults (19–27 y), excluding smokers, medication users, pregnant women, and oral-contraceptive users, which limits generalizability.
- Evident from the text: the study used a single 24-IU intranasal oxytocin dose and one post-treatment time point, with no dose-response or longer-term behavioral follow-up; the male likeability decrease was only marginal (P = 0.09).
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17 Not checked yet · 14 Own result · 7 Own interpretation · 2 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This yielded a significant treatment × sex interaction in the left amygdala for social criticism vs. praise ( k = 262, familywise error (FWE) corrected P FWE = 0.001)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Here we show that intranasal oxytocin treatment produces sex- and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Extraction of parameter estimates from this cluster revealed that OXT enhanced in males ( t 35 = 3.1, P = 0.004, Cohen ' s d = 1.02) but attenuated in females ( t 35 = -3.18, P = 0.003, Cohen ' s d = 1.09) left amygdala responses to criticizing vs. praising other people”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Importantly, no such effect was found in the parallel object-directed condition”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“A functional connectivity analysis revealed a treatment × sex interaction for left amygdala coupling with the right insula ( t 70 = 4.19, P FWE = 0.009)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Individuals targeting nonsocial objects (5.1 ± 0.07) were rated more likeable than those targeting other people (4.76 ± 0.07).”
plainn = 74- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Probabilistic mapping indicated that the effect was mainly localized in the laterobasal subregion of the amygdala”
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Previous research has shown that the amygdala has different responses to positive and negative valence social information in men and women (11)”
What the sources say
- Not checked yetcites [11] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, in response to couple conflict, OXT decreased sympathetic activity and arousal in women but increased them in men (6).”
What the sources say
- Not checked yetcites [6] source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 17
- Probably not a substantial claim. 4
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Extracted parameter estimates further demonstrated that OXT increased coupling strength in males ( t 35 = 3.59, P = 0.001, Cohen ' s d = 1.18) but reduced it in females ( t 35 = -2.29, P = 0.03, Cohen ' s d = 0.76) for criticizing vs. praising others”
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, male ratings were generally lower than female ones following OXT ( F 1, 70 = 6.83, P = 0.01, η 2 P = 0.09) but not PLC.”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The likeability of faces paired with criticism was rated lowest [mean ( M ) ± SE, 3.83 ± 0.1] and those paired with praise was rated highest (6 ± 0.09).”
plainn = 74- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In line with the fMRI findings, a significant treatment × sex interaction was found ( F 1, 70 = 7.08, P = 0.01, η 2 P = 0.09), revealing that whereas OXT relative to PLC increased females ' overall likeability ratings ( F 1, 70 = 4.25, P = 0.04, η 2 P = 0.06), in males it tended to decrease them ( F 1, 70 = 2.89, P = 0.09, η 2 P = 0.04)”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with greater reactivity in men to those who criticized others ( t 35 = 3.22, P = 0.003, Cohen ' s d = 1.04) but in women to those who praised them ( t 35 = 2.45, P = 0.019, Cohen ' s d = 0.82)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with connectivity being weaker in females ( t 35 = -2.74, P = 0.01, Cohen ' s d = 0.9) but stronger in males ( t 35 = 2.49, P = 0.02, Cohen ' s d = 0.81) for criticizers, and for praisers, in contrast, stronger in females ( t 35 = 2.03, P = 0.05, Cohen ' s d = 0.68) but weaker in males ( t 35 = -2.15, P = 0.04, Cohen ' s d = 0.71)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Individuals paired with positive valence characteristics are rated as more likeable and approachable but the opposite for those with negative information (22).”
What the sources say
- Not checked yetcites [22] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In particular, behavioral studies have reported that whereas OXT tends to facilitate positive social judgments (7), social approach (8), kinship recognition (5), and altruism (9) in women, in men it can facilitate negative social judgments (7), social avoidance (10), competitor recognition (5), and selfishness (9).”
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Importantly, this region plays a key role in processing social salience (18) and controlling approach and avoidance behaviors (10), which OXT has been shown to modulate (3, 4, 6, 19).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Recent studies in both monkeys and humans have suggested that it has not only evolved a more extensive role in social cognition in female primates but also become progressively used by males in this domain (3).”
What the sources say
- Not checked yetcites [3] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“During social interactions, we make rapid judgments about new people that determine whether to approach or avoid and shape our future interactions with them (21).”
What the sources say
- Not checked yetcites [21] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The partial correlation between likeability and extraction of OXT-altered functional connectivity was computed controlling for STAI and PANAS scores because OXT might modulate anxiety and mood (45, 46).”
What the sources say
- Not checked yetcites [45] Guastella AJ, Howard AL, Dadds MR, Mitchell P, Carson DS (2009) A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology 34(6):917 -923. source
- Not checked yetcites [46] Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54(12):1389 -1398. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, our findings demonstrate that whereas OXT enhances the salience of positive social attributes in women, it makes men focus more on negative ones.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, other studies have also reported that OXT effects on amygdala responses often occur with concurrent changes in its connections with, and activation of, the insula (27 -29).”
What the sources say
- Not checked yetcites [27] Rilling JK, et al. (2012) Effects of intranasal oxytocin and vasopressin on cooperative behavior and associated brain activity in men. Psychoneuroendocrinology 37(4): 447 -461. source
- Not checked yetcites [28] Striepens N, et al. (2012) Oxytocin facilitates protective responses to aversive social stimuli in males. Proc Natl Acad Sci USA 109(44):18144 -18149. source
- Not checked yetcites [29] Riem MM, et al. (2012) No laughing matter: Intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter. Neuropsychopharmacology 37(5):1257 -1266. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, our neuroimaging results provide the first evidence, to our knowledge, that OXT exerts markedly different neural effects in men and women, with greater left amygdala response in women to individuals exhibiting socially but not nonsocially directed praise although in men to those who criticize others.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The neural basis of the opposing sex-dependent behavioral effects of oxytocin has not been established.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Subjects rated the faces as emotionally neutral ( M ± SD, 4.98 ± 0.15) and average in attractiveness (4.37 ± 0.35) and trustworthiness (4.87 ± 0.32) using 9-point Likert scales.”
plainn = 36- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
What the sources say
- Not checked yetcites [14] source
- Not checked yetcites [15] source
- Not checked yetcites [16] source
- Not checked yetcites [17] source
- Not checked yetcites [30] Petrovic P, Kalisch R, Singer T, Dolan RJ (2008) Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci 28(26):6607 -6615. source
- Not checked yetcites [31] Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58(4): 639 -650. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Additionally, the lack of OXT modulation in a face-alone control condition argues against confounding effects of OXT on face perception per se (25) or face sex (Tables S2 and S3).”
What the sources say
- Not checked yetcites [25] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The neural basis of the opposing sex-dependent behavioral effects of oxytocin has not been established.
“The neural basis of these opposing sex-dependent behavioral effects of OXT has not, however, been established.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 [49]
In the citing paper
“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 [49]
In the citing paper
“For the oxytocin-fMRI and behavioral oxytocin-replication experiments, we recruited only male participants to avoid potential confounds of sex differences in oxytocin effects 21,51 , consistent with previous studies examining oxytocin effects on social cognition.”
From Oxytocin modulates social value representations in the amygdala (2019) · cites this paper as [51]
In the citing paper
“As a result of these actions OXT treatment decreases amygdala activity in response to negative/ fearful emotions (Fig. 3) and increases the activity of cortical and subcortical regions, often in a sex-specific way (Gao et al., 2016).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Gao et al., 2016
In the citing paper
“Based on a growing number of findings suggesting sex-dependent effects of OXT on social cognition (Chen et al., 2016; Gao et al., 2016; Luo et al., 2017), the second experiment additionally explored whether OXT differentially affects empathic processing in men and women.”
From Oxytocin Enhancement of Emotional Empathy: Generalization Across Cultures and Effects on Amygdala Activity (2018) · cites this paper as Gao et al., 2016
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Not confirmedz = 2.41reported p = .008 · recomputed p = .016
“z = 2.41, p = .008”
- Not confirmedz = 2.51reported p = .006 · recomputed p = .012
“z = 2.51, p = .006”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Results
“Fisher ' s z = 2.41, P = 0.008) and praising people in females (OXT, r = 0.5, P = 0.04; PLC, r = -0.35; P = 0.26; Fisher ' s z = 2.51, P = 0.006)”
§ Materials and Methods
“All reported P values were twotailed, and P < 0.05 was considered significant.”
Citations
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Biased Oxytocinergic Modulation of Midbrain Dopamine Systems
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Metadata
- Authors
- Gao, S., Becker, B., Luo, L., Geng, Y., Zhao, W., Yin, Y., Hu, J., Gao, Z., Gong, Q., Hurlemann, R., Yao, D., & Kendrick, K. M.
- Affiliations
- University of Electronic Science and Technology of China (CN)
- Sichuan University (CN)
- Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, 53105 Bonn, Germany
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-06-20
- Volume
- 113
- Issue
- 27
- Pages
- 7650-7654
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4941426
- OpenAlex
- W2463712686
- Semantic Scholar
- af05fbad29f511e2370f503c16a26d83b21df3a2
- Cited by
- 186
- References
- 48
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 11 · 2023: 6 · 2022: 16 · 2021: 27 · 2020: 30 · 2019: 32 · 2018: 17 · 2017: 24 · 2016: 4
- FWCI
- 40.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31530032)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Evolutionary Psychology and Human Behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin, sex differences, amygdala activation, social cognition, intranasal oxytocin, social bonding, prosocial behavior, antisocial behavior
- MeSH terms
- Adult, Amygdala, Female, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Sex Characteristics, Social Behavior, Young Adult, Sociological Factors
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