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Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder
Open accessAbstract
Patients with generalized social anxiety disorder (GSAD) exhibit heightened activation of the amygdala in response to social cues conveying threat (eg, fearful/angry faces). The neuropeptide oxytocin (OXT) decreases anxiety and stress, facilitates social encounters, and attenuates amygdala reactivity to threatening faces in healthy subjects. The goal of this study was to examine the effects of OXT on fear-related amygdala reactivity in GSAD and matched healthy control (CON) subjects. In a functional magnetic resonance imaging study utilizing a double-blind placebo-controlled within-subjects design, we measured amygdala activation to an emotional face matching task of fearful, angry, and happy faces following acute intranasal administration of OXT (24 IU or 40.32 μg) and placebo in 18 GSAD and 18 CON subjects. Both the CON and GSAD groups activated bilateral amygdala to all emotional faces during placebo, with the GSAD group exhibiting hyperactivity specifically to fearful faces in bilateral amygdala compared with the CON group. OXT had no effect on amygdala activity to emotional faces in the CON group, but attenuated the heightened amygdala reactivity to fearful faces in the GSAD group, such that the hyperactivity observed during the placebo session was no longer evident following OXT (ie, normalization). These findings suggest that OXT has a specific effect on fear-related amygdala activity, particularly when the amygdala is hyperactive, such as in GSAD, thereby providing a brain-based mechanism of the impact of OXT in modulating the exaggerated processing of social signals of threat in patients with pathological anxiety.
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In the citing paper
“Some research indicates that OXT could be influential in the treatment of established SAD (Labuschagne et al, 2010) and PTSD (Olff et al, 2014).”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Labuschagne et al, 2010
In the citing paper
“Heightened amygdala reactivity has been strongly linked to these social threat-related impairments and many have posited that the amygdala is an important therapeutic target for the management of GSAD (Labuschagne et al, 2010;Phan et al, 2006).”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“Heightened amygdala reactivity has been strongly linked to these social threat-related impairments and many have posited that the amygdala is an important therapeutic target for the management of GSAD (Labuschagne et al, 2010;Phan et al, 2006).”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“We have extended these studies to examine the effects of OXT on amygdala reactivity to social threat in GSAD (Labuschagne et al, 2010) and found that OXT attenuated (or normalized) the hyperactive amygdala reactivity to fearful faces in GSAD patients.”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“These effects were not observed in response to angry or happy faces.”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“We first confirmed using a whole-brain, 2 (session: PBO, OXT)  2 (group: HC, GSAD) analysis of variance (ANOVA) that consistent with Labuschagne et al (2010), there was a significant group  drug interaction on left amygdala reactivity to fearful faces (peak MNI coordinates: ( À 24, À 2, À 22), Z ¼ 2.77, k ¼ 81, po0.05, small volume corrected), such that OXT attenuated (or normalized) the hypera”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“The EFMT task has previously been described in detail elsewhere (Labuschagne et al, 2010), and has been used in previous pharmaco-fMRI studies to probe drug effects on amygdala activation (Kirsch et al, 2005;Paulus et al, 2005;Phan et al, 2008;Labuschagne et al, 2010) and amygdala functional connectivity (Gorka et al, 2013).”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“This finding of divergent effects is consistent with the two other OXT administration studies from our group (Dodhia et al, 2014;Labuschagne et al, 2010)”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Labuschagne et al, 2010
In the citing paper
“We had previously shown that acute OXT exerted effects on the amygdala and mPFC/ACC during the processing of threat and other negative emotions (Labuschagne et al, 2010(Labuschagne et al, , 2011)).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Labuschagne et al, 2010
In the citing paper
“In two recent task-based studies, we showed that OXT attenuates heightened activity in the amygdala of GSAD patients after viewing fearful faces (Labuschagne et al, 2010)”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Labuschagne et al, 2010
In the citing paper
“This is also agreement with decreasing amygdala activation to fearful faces in healthy (45), as well as anxious (46), humans with OT administration.”
From Neuroendocrinology of Parental Response to Baby‐Cry (2011) · cites this paper as [46]
In the citing paper
“Importantly, IN-OT attenuates heightened amygdala reactivity to fearful faces in patients with generalized social anxiety disorder (GSAD) (Labuschagne et al. 2010).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Labuschagne et al. 2010
In the citing paper
“there are increasing evidence for the role of OT in reducing anxiety, fear, and stress, in part by dampening amygdala activity”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Labuschagne et al. 2010
In the citing paper
“IN-OT restores functional connectivity between subcortical regions such as amygdala and frontal areas, including the ACC and mPFC”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Labuschagne et al. 2010
In the citing paper
“reduces the heightened amygdala reactivity to fearful faces in patients with generalized anxiety disorders”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Labuschagne et al. 2010
In the citing paper
“Results indicate that the tested type of intranasal OT delivery -but not peripherally delivered OT that produces similar blood levels -replicates prior findings of reduced right amygdala activation in response to emotional stimuli after OT treatment (Domes et al., 2007;Labuschagne et al., 2010;Petrovic et al., 2008).”
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 Labuschagne et al., 2010
In the citing paper
“Of note, other studies have reported similar results after administration of 24 IU (Domes et al., 2007;Kanat et al., 2015;Labuschagne et al., 2010), however, the dosages are difficult to compare between experiments as these studies used traditional nasal spray devices to administer OT.”
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 Labuschagne et al., 2010
In the citing paper
“normalized the abnormal neural responses to negative social stimuli in patients with social anxiety disorder (32, 33).”
From Placebo treatment facilitates social trust and approach behavior (2018) · cites this paper as [32]
In the citing paper
“This fits with the hypothesis that OT administration effects may be especially beneficial in those who lack proficiency in fear regulation (Labuschagne et al, 2010) or social functioning (Olff et al, 2013;Weisman and Feldman, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Labuschagne et al, 2010
In the citing paper
“In addition, functional MRI (fMRI) studies have shown that OT administration dampened amygdala reactivity toward emotional stimuli in healthy males (Kirsch et al, 2005), males with generalized social anxiety disorder (GSAD; Labuschagne et al, 2010) and females with borderline personality disorder (BPD; Bertsch et al, 2013), although findings for females have been mixed (Domes et al, 2010).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Labuschagne et al, 2010
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Metadata
- Authors
- Labuschagne, I., Phan, K. L., Wood, A., Angstadt, M., Chua, P., Heinrichs, M., Stout, J. C., & Nathan, P. J.
- Affiliations
- Monash University (AU)
- University of Michigan (US)
- Royal Children's Hospital (AU)
- University of Freiburg (DE)
- University of Cambridge (GB)
- Corresponding author
- Nathan, Pradeep J
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2010-08-18
- Volume
- 35
- Issue
- 12
- Pages
- 2403-2413
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055328
- OpenAlex
- W2116280488
- Cited by
- 549
- References
- 91
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 20 · 2023: 62 · 2022: 22 · 2021: 22 · 2020: 47 · 2019: 27 · 2018: 35 · 2017: 48 · 2016: 37 · 2015: 54 · 2014: 44 · 2013: 43 · 2012: 28
- FWCI
- 45.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Aston Publications Explorer (Aston University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (114788)
- National Institute of Mental Health (MH076198, K23MH076198)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, generalized social anxiety disorder, amygdala reactivity, fear, emotional face processing, amygdala hyperactivity, intranasal administration, social danger
- MeSH terms
- Administration, Intranasal, Adult, Amygdala, Anxiety Disorders, Brain Mapping, Double-Blind Method, Facial Expression, Fear, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Oxytocin, Placebos, Psychomotor Performance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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