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Oxytocin increases amygdala reactivity to threatening scenes in females
Abstract
The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants' eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants' gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen.
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“Likewise, sex differences in the effects of AVP and OXT manipulations on behavioral and brain responses have been reported in adult humans (Thompson et al., 2006; Domes et al., 2007, 2010; Lischke et al., 2012; Rilling et al., 2014).”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Lischke et al., 2012
In the citing paper
“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 [15]
In the citing 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.”
From Oxytocin, the peptide that bonds the sexes also divides them (2016) · cites this paper as [17]
In the citing paper
“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 [12]
In the citing paper
“A pragmatic approach guided by prior fMRI OT research (Domes et al., 2007(Domes et al., , 2010;;Kirsch et al., 2005;Lischke et al., 2012) was taken for sample size determination reflecting the phase 1 status of OT administration using the Breath Powered device and the complex nature of the study design.”
From Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial (2016) · cites this paper as Lischke et al., 2012
In the citing paper
“Studies of intranasally delivered exogenous OXT (OXT IN ) have shown that the peptide produces anxiolytic-like effects as a result of dampened amygdala reactivity to threat (Eckstein and Hurlemann, 2013;Domes et al, 2007, but see Lischke et al, 2012)”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Lischke et al, 2012
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Self-citationIntranasal oxytocin reduces social perception in women: Neural activation and individual variation
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“102,103 The effect, at least in men, may be potentially useful in mitigating or attenuating the expression of PTSD. 104 efficacy of particular pharmaceutical agents in the treatment of clinical anxiety has directed exploration of candidate genes and common variants in receptors and transporter…”
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“In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism.”
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“Lastly, there has been a growing debate on whether OT facilitates emotion recognition by focusing more attention to the eye regions (e.g. Guastella et al., 2008; Lischke et al., 2012a).”
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“Activation results Regions x y z T Cluster size P”
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“…oxytocin effects on amygdala neural responses to negative affective stimuli tend to be increased in women but decreased in men (Gao et al., 2016; Lischke et al., 2012), which is further supported by a sex-dependent receptor distribution in the amygdala (in non-primate mammals; Francis et al.,…”
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“…particularly for threatening emotional stimuli such as fear (Domes et al., 2007; Huber et al., 2005; Kirsch et al., 2005; Labuschagne et al., 2010; Lischke et al., 2012) However in humans, studies have also reported that in some threat contexts OXT can have anxiogenic effects (Striepens et al.,…”
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Pituitary Hormones and Orofacial Pain
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Oxytocin promotes species-relevant outgroup attention in bonobos and chimpanzees
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Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in womenPreprint
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Oxytocin differentially modulates the early neural responses to faces and non-social stimuli
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“Crucially, the present ERP-OT face findings cannot be extended to men because OT’s effects are sexually dimorphic (Domes et al. , 2010; Lischke et al. , 2012; Gao et al. , 2016).”
BackgroundOral Oxytocin Blurs Sex Differences in Amygdala Responses to Emotional Scenes
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“Contrarily, some research shows that intranasal oxytocin leads to the enhancement of amygdala reactivity to scenes depicting threats (both social and non-social) in females [128,129].”
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“…2) We intentionally recruited male (n = 227) and female (n = 218) participants to explore if the selective enhancement of social memory observed in Rimmele’s study (3) could be extended to heterosexual women, especially given that oxytocin’s cognitive effects can be sex - specific (17 –20).”
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“In contrast, healthy women administered OXT exhibited greater amygdala responses when viewing threatening scenes [27].”
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Oxytocin - not only a "social" neuropeptide
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Oxytocin and Social Behavior—Based on Social Salience and Situation Strength
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“Furthermore, this hormone plays a crucial role in stress regulation, facilitating a return to homeostasis following a psychosocial threat by increasing parasympathetic control and inhibiting activity in the amygdala (58 – 60), potentially promoting stress-attenuating processes.”
Influential
Metadata
- Authors
- Lischke, A., Gamer, M., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., Herpertz, S. C., & Domes, G.
- Affiliations
- Heidelberg University (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Rostock (DE)
- University of Freiburg (DE)
- Corresponding author
- Lischke, Alexander
- Domes, Gregor
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 37
- Issue
- 9
- Pages
- 1431-1438
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2042669554
- Cited by
- 194
- References
- 48
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 14 · 2018: 14 · 2017: 25 · 2016: 16 · 2015: 22 · 2014: 23 · 2013: 23 · 2012: 9
- FWCI
- 37.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, amygdala, threat processing, sex differences, female, intranasal administration, eye movements, social danger, sex steroids, progesterone, estrogen
- MeSH terms
- Administration, Intranasal, Adult, Amygdala, Double-Blind Method, Emotions, Eye Movements, Facial Expression, Fear, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Oxytocin, Cross-Over Studies, Functional Neuroimaging
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