Cited by 1,639Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyMemory and Neural Mechanisms

Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans

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Kirsch, Peter, Esslinger, Christine, Chen, Qiang, Mier, Daniela, Lis, Stefanie, Siddhanti, Sarina, Gruppe, Harald, Mattay, Venkata S. +2 more·2005·The Journal of Neuroscience

Abstract

In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.

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Crossref · 10.1523/jneurosci.3984-05.2005

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  • Neuroimaging studies in humans have largely substantiated the view that human attachment relies on conserved hormonal machinery.

    “Neuroimaging studies in humans have largely substantiated this view.”

    From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [41]

    The Introduction (page unavailable) describes oxytocin as evolutionarily preserved and important for prosocial behavior across species. The Discussion (page unavailable) reports that oxytocin affects human brain circuitry involved in social processing, but the study tested responses to fearful stimuli, not attachment. It therefore supports a conserved hormonal role in social cognition without directly establishing that human attachment relies on it. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • OT's effects in the olfactory bulb on social recognition are mediated by norepinephrine.

    “It is known, however, that OTs effects in the olfactory bulb on social recognition are mediated by norepinephrine [75, 76].”

    From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [76]

    The Introduction (page unavailable) links oxytocin to social recognition, citing restoration of recognition in mice after injection into the medial amygdala. It does not say that oxytocin acts in the olfactory bulb or that norepinephrine mediates the effect; searches for those mechanisms found no supporting passage. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • Oxytocin is involved in counteracting fear.

    “as well as in counteracting fear (Kirsch et al. 2005)”
  • Administration of oxytocin correlated with a decrease of amygdala activity following exposure to interpersonally threatening visual stimuli (angry or afraid faces).

    “Administration of oxytocin, a hormone associated with social bonding, correlated with a decrease of amygdala activity following exposure to interpersonally threatening visual stimuli (angry or afraid faces; Charuvastra & Cloitre, 2008; Kirsch et al., 2005).”
  • Mothers who observe photographs of their own infants compared against matched controls show heightened activation in brain areas rich in oxytocin, vasopressin, and dopamine neuroreceptors.

    “Mothers who observe photographs of their own infants compared against matched controls show heightened activation in brain areas rich in oxytocin, vasopressin, and dopamine neuroreceptors [41, 42].”

    From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [41]

    The Subjects section describes male participants who viewed threatening faces and scenes after receiving oxytocin or placebo, not mothers viewing photographs of their infants. The Results report reduced amygdala activation under oxytocin; no passage found in our copy addresses the claimed maternal response or the three receptor-rich brain areas (searched: infant photographs, mother, dopamine). (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Authors
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V. S., Gallhofer, B., & Meyer-Lindenberg, A.
Affiliations
  • Justus-Liebig-Universität Gießen (DE)
  • National Institutes of Health (US)
Venue
The Journal of Neuroscience
Published
2005-12-07
Volume
25
Issue
49
Pages
11489-11493
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2121748618
Cited by
1,639
References
39
Citations by year
2026: 31 · 2025: 32 · 2024: 45 · 2023: 43 · 2022: 44 · 2021: 79 · 2020: 97 · 2019: 82 · 2018: 85 · 2017: 103 · 2016: 99 · 2015: 107 · 2014: 119 · 2013: 122 · 2012: 119
FWCI
67.02
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • KOPS (University of Konstanz) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
oxytocin, amygdala, fear conditioning, social cognition, neural circuits, intranasal administration, trust, anxiety, social anxiety disorder, autism spectrum disorder, fear extinction
MeSH terms
Adolescent, Adult, Cognition, Double-Blind Method, Fear, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Oxytocin, Photic Stimulation, Psychomotor Performance, Social Behavior

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