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Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: Salience processing and fear inhibition processes
Abstract
About ten percent of people experiencing a traumatic event will subsequently develop post-traumatic stress disorder (PTSD). PTSD is characterized by an exaggerated fear response which fails to extinguish over time and cannot be inhibited in safe contexts. The neurobiological correlates of PTSD involve enhanced salience processing (i.e. amygdala, dorsal anterior cingulate cortex (dACC) and anterior insula (AI) hyperactivity), and reduced top-down inhibitory control over this fear response (i.e. dorsal and ventromedial prefrontal cortex (vmPFC) hypoactivity and diminished structural and functional connectivity between the vmPFC, hippocampus and amygdala). Therefore, dampening the exaggerated fear response (i.e. by reducing amygdala hyperactivity) and enhancing top-down inhibitory control (i.e. by promoting prefrontal control over the amygdala) during psychotherapy is an important target for medication-enhanced psychotherapy (MEP) in PTSD patients. Since the neuropeptide oxytocin (OT) has been found to act on these two processes, we propose that OT is a promising pharmacological agent to boost treatment response in PTSD. Human fMRI studies indicate that intranasal OT attenuates amygdala (hyper)activity and enhances connectivity of the amygdala with the vmPFC and hippocampus, resulting in increased top-down control over the fear response. In addition, intranasal OT was found to attenuate amygdala-brainstem connectivity and to change activity and connectivity in nodes of the salience network (i.e. AI and dACC). Furthermore, OT administration may modulate hypothalamus-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) function and may enhance social behaviour, which could be beneficial in the therapeutic alliance. We also discuss contextual and interindividual factors (e.g. gender and social context) which may influence the effectiveness of OT in MEP. In all, we propose that intranasal OT given prior to each psychotherapy session may be an effective additive treatment to boost treatment response in PTSD.
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In the citing paper
“These findings suggest that oxytocin has potential as an adjunctive therapy for extinction-based PTSD treatments such as PE (Koch et al., 2014; Olff et al., 2010).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Koch et al., 2014
In the citing paper
“Prevailing hypotheses suggest that oxytocin may uniquely help mitigate barriers to engaging in behavioral treatments that specifically target avoidance (Preckel et al., 2014), which would thereby allow patients who might otherwise be unable to tolerate PE to engage effectively, complete the treatment, obtain an adequate therapeutic dose, and experience long-term remission of PTSD (Frijling et al.,”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Koch et al., 2014
In the citing paper
“OT has been suggested as a promising pharmacological agent to enhance treatment response in PTSD (Koch et al, 2014;Olff et al, 2010).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Koch et al, 2014
In the citing paper
“oxytocin has been repeatedly proposed as an effective novel drug treatment for PTSD [3, 58]”
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Metadata
- 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
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 40
- Pages
- 242-256
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W1977778322
- Cited by
- 123
- References
- 114
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 9 · 2018: 19 · 2017: 15 · 2016: 9 · 2015: 16 · 2014: 8
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- intranasal oxytocin, post-traumatic stress disorder, salience processing, fear inhibition, amygdala hyperactivity, salience network, anterior insula, dorsal anterior cingulate cortex, hypothalamic-pituitary-adrenal axis, autonomic nervous system, social behavior, therapeutic relationship, gender differences, treatment response
- MeSH terms
- Adaptation, Psychological, Administration, Intranasal, Animals, Combined Modality Therapy, Fear, Humans, Mental Processes, Oxytocin, Psychotherapy, Stress Disorders, Post-Traumatic
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