Background <p>Anxiety and stress-related disorders are associated with abnormal neural reactivity and connectivity, particularly in the amygdala and prefrontal regions. Intranasal oxytocin (OXT) has emerged as a potential modulator of these neural circuits, but evidence for its clinical efficacy remains mixed. This systematic review aims to evaluate the effects of intranasal OXT on brain function in anxiety and stress-related disorders using functional Magnetic Resonance Imaging (fMRI) studies.</p> Methods <p>Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane central) were queried for English publications up to February 2025. The search involved utilizing various keyword combinations, including “Stress” OR “Anxiety” AND " Oxytocin”. No restrictions were imposed on these terms or any synonyms incorporated into the search approach. The Cochrane Risk of Bias Tool for randomized controlled trials (RCTs) was employed to assess the quality of the included studies.</p> Results <p>We included 16 RCTs out of a total of 996 studies in this review. The findings were categorized according to specific disorder types: participants with trauma-related PTSD (<i>n</i> = 11), those diagnosed with social anxiety disorder (SAD) (<i>n</i> = 5). OXT showed promise as a treatment for conditions associated with stress and anxiety. In PTSD patients, OXT improved functional connectivity (FC) between the amygdala and cortical areas and altered amygdala reactivity, effects that were influenced by factors such as sex, symptom severity, and history of trauma or anxiety. For SAD, OXT enhanced amygdala-prefrontal cortex connectivity and decreased reactivity between the insula and amygdala. Additionally, differences between males and females in these stress related and anxiety disorders appear to affect how OXT exerts its effects.</p> Conclusions <p>This review highlights the potential of intranasal OXT as a promising treatment for stress related and anxiety disorders, showing its ability to modulate key brain regions involved in emotion regulation and cognition, such as the amygdala, prefrontal cortex, insula, and striatum. While further research is needed to optimize its use, intranasal OXT offers a viable biological-based therapy, with effects that may differ between sexes.</p> Clinical trial number <p>Not applicable.</p>

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Exploring the efficacy of intranasal oxytocin (OXT) for anxiety and stress-related disorders through functional magnetic resonance imaging (fMRI) study: a systematic review

  • Reza Moshfeghinia,
  • Erfan Sanaei,
  • Kiarash Kavari,
  • Amir Mohammad Barzegari,
  • Amir Mahmoud Ahmadzadeh,
  • Melika Arab Bafrani,
  • Adrina Habibzadeh,
  • Mahsa Boroon,
  • Mohammadreza Shalbafan

摘要

Background

Anxiety and stress-related disorders are associated with abnormal neural reactivity and connectivity, particularly in the amygdala and prefrontal regions. Intranasal oxytocin (OXT) has emerged as a potential modulator of these neural circuits, but evidence for its clinical efficacy remains mixed. This systematic review aims to evaluate the effects of intranasal OXT on brain function in anxiety and stress-related disorders using functional Magnetic Resonance Imaging (fMRI) studies.

Methods

Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane central) were queried for English publications up to February 2025. The search involved utilizing various keyword combinations, including “Stress” OR “Anxiety” AND " Oxytocin”. No restrictions were imposed on these terms or any synonyms incorporated into the search approach. The Cochrane Risk of Bias Tool for randomized controlled trials (RCTs) was employed to assess the quality of the included studies.

Results

We included 16 RCTs out of a total of 996 studies in this review. The findings were categorized according to specific disorder types: participants with trauma-related PTSD (n = 11), those diagnosed with social anxiety disorder (SAD) (n = 5). OXT showed promise as a treatment for conditions associated with stress and anxiety. In PTSD patients, OXT improved functional connectivity (FC) between the amygdala and cortical areas and altered amygdala reactivity, effects that were influenced by factors such as sex, symptom severity, and history of trauma or anxiety. For SAD, OXT enhanced amygdala-prefrontal cortex connectivity and decreased reactivity between the insula and amygdala. Additionally, differences between males and females in these stress related and anxiety disorders appear to affect how OXT exerts its effects.

Conclusions

This review highlights the potential of intranasal OXT as a promising treatment for stress related and anxiety disorders, showing its ability to modulate key brain regions involved in emotion regulation and cognition, such as the amygdala, prefrontal cortex, insula, and striatum. While further research is needed to optimize its use, intranasal OXT offers a viable biological-based therapy, with effects that may differ between sexes.

Clinical trial number

Not applicable.