Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder
Open accessAbstract
The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.
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The small number of existing rsfMRI oxytocin-administration studies use seed-based analyses that do not allow for hypothesis-free examination across the connectome.
“the small number of existing rsfMRI oxytocin-administration studies5, 13, 19, 20 use seed-based analyses that do not allow for hypothesis-free examination across the connectome.”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [20]
In these PTSD subjects, IN-OT restored functional connectivity to levels observed in healthy controls and decreased subjective experiences of anxiety and nervousness.
“In these subjects, IN-OT restored functional connectivity to levels observed in healthy controls and also decreased subjective experiences of anxiety and nervousness.”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [47]
In one study using resting state fMRI, females with PTSD displayed increased connectivity between the right basolateral amygdala and right anterior cingulate cortex while males with PTSD displayed decreased activity between the right centromedial amygdala and right ventromedial PFC.
“In one study using resting state fMRI, females with PTSD displayed increased connectivity between the right basolateral amygdala and right anterior cingulate cortex while males with PTSD displayed decreased activity between the right centromedial amygdala and right ventromedial PFC [47].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [47]
Evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples and in individuals with PTSD.
“evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples (Sripada et al., 2013) and in individuals with PTSD (Koch et al., 2016).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Koch et al., 2016
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Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women
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“The small number of existing rsfMRI oxytocinadministration studies (Sripada et al., 2013; Watanabe et al., 2015; Ebner et al., 2016; Koch et al., 2016) use seed-based analyses that do not allow for hypothesis-free examination across the connectome.”
Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities
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Self-citationTranslational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
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- Authors
- Koch, S. B. J., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Koch, Saskia B J
- Venue
- Neuropsychopharmacology
- Published
- 2016-01-07
- Volume
- 41
- Issue
- 8
- Pages
- 2041-2051
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4908648
- OpenAlex
- W2235676486
- Cited by
- 132
- References
- 55
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 19 · 2020: 14 · 2019: 14 · 2018: 20 · 2017: 20 · 2016: 8
- FWCI
- 27.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- ZonMw (91210041)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, post-traumatic stress disorder, intranasal administration, amygdala functional connectivity, basolateral amygdala, centromedial amygdala, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, subjective anxiety, sex differences, police officers, trauma exposure
- MeSH terms
- Administration, Intranasal, Adult, Amygdala, Anxiety, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Oxytocin, Stress Disorders, Post-Traumatic, Young Adult
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