Effects of intranasal oxytocin on amygdala reactivity to emotional faces in recently trauma-exposed individuals
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UNLABELLED: There is a need for effective, early post-trauma preventive interventions for post-traumatic stress disorder (PTSD). Attenuating amygdala hyperreactivity early post-trauma, a likely PTSD vulnerability factor, may decrease PTSD risk. Since oxytocin modulates amygdala reactivity to emotional stimuli, oxytocin administration early post-trauma may be a promising candidate for PTSD prevention. In a randomized double-blind placebo-controlled fMRI study, we investigated effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening. We explored treatment interactions with sex. Participants were scanned within 11 days post-trauma. Compared with placebo, oxytocin significantly increased right amygdala reactivity to fearful faces. There was a significant treatment by sex interaction on amygdala reactivity to neutral faces, with women showing increased left amygdala reactivity after oxytocin. These findings indicate that a single oxytocin administration may enhance fearful faces processing in recently trauma-exposed individuals and neutral faces processing in recently trauma-exposed women. These observations may be explained by oxytocin-induced increased salience processing. Clinical implications of these findings for PTSD prevention should be further investigated. TRIAL REGISTER: Netherlands Trial Registry; Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology (BONDS); NTR3190; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 3190.
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In the clinical population, the amygdala has been implicated in the pathogenesis of psychiatric sequelae.
“In the clinical population, the amygdala has also been implicated in the pathogenesis of psychiatric sequelae.”
From Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior (2017) · cites this paper as Frijling et al., 2016
Patients with depression show alterations in amygdala function and its connectivity with other brain areas.
“For instance, patients with depression also show alterations in amygdala function and its connectivity with other brain areas (Elzinga et al., 2003, Frijling et al., 2016, Jedd et al., 2015, McEwen, 2003, Ressler and Mayberg, 2007, Savitz and Drevets, 2009, Sibille et al., 2009, Teicher et al., 2003).”
From Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior (2017) · cites this paper as Frijling et al., 2016
In recently trauma-exposed individuals, intranasal oxytocin within 10 days posttrauma increased amygdala reactivity to fearful faces and decreased amygdala-ventrolateral prefrontal functional connectivity after a trauma reminder.
“In recently traumaexposed individuals, however, intranasal oxytocin within 10 days posttrauma increased amygdala reactivity to fearful faces (27) and decreased amygdala-ventrolateral prefrontal functional connectivity after a trauma reminder (28).”
From Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients (2017) · cites this paper as [27]
Recent neuroimaging studies have reported oxytocin-induced increases in neural activation in regions, including the amygdala, which are associated with processing of salience and arousal.
“These studies have reported oxytocin-induced increases in neural activation in regions, including the amygdala, which are associated with processing of salience and arousal (Frijling et al., 2016;Gorka et al., 2015;Koch et al., 2016).”
From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Frijling et al., 2016
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Helpman, L., Zhu, X., Suarez-Jimenez, B., Lazarov, A., Monk, C., & Neria, Y. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0854-y · Cited by 82 · see citing works
Frijling, J. L., van Zuiden, M., Koch, S. B. J., Nawijn, L., Veltman, D. J., & Olff, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.278 · Cited by 60 · see citing works
Self-citationLeppanen, J., Ng, K. W., Kim, Y.-R., Tchanturia, K., & Treasure, J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.041 · Cited by 45 · see citing works
- Authors
- Frijling, J. L., van Zuiden, M., Koch, S. B. J., Nawijn, L., Veltman, D. J., & Olff, M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Department of Psychiatry and
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Arq Psychotrauma Expert Group (NL)
- Venue
- Social Cognitive and Affective Neuroscience
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-17
- Volume
- 11
- Issue
- 2
- Pages
- 327-336
- ISSN
- 1749-5016 (ISSN-L)
- 1749-5024
- PMC
- PMC4733344
- OpenAlex
- W2234999694
- Cited by
- 62
- References
- 74
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 1 · 2014: 1
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Social Cognitive and Affective Neuroscience (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- ZonMw (91210041)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Keywords
- intranasal oxytocin, amygdala reactivity, emotional face processing, fearful faces, trauma exposure, post-traumatic stress disorder prevention, sex differences, salience processing
- MeSH terms
- Administration, Intranasal, Adult, Amygdala, Double-Blind Method, Emotions, Facial Expression, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Oxytocin, Stress Disorders, Post-Traumatic, Young Adult
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