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Oxytocin׳s role in anxiety: A critical appraisal
Abstract
A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety states, anxiety-related traits, and moreover, that this system may be a target for the development of novel anxiolytic treatments. However, studies of OT's acute and chronic effects on various aspects of anxiety have produced mixed results. In this forward-looking review, we discuss the myriad phenomena to which the term "anxiety" is applied in the OT literature and the problem this presents developing a coherent picture of OT's role in anxiety. We then survey several different fields of research that support the role of the OT system in human anxiety, including evolutionary perspectives, translational and neuroimaging research, genetic studies, and clinical trials of intranasal OT. As an outgrowth of this data, we propose a "bowtie" model of OT's role at the interface of social attachment and anxiety. We next direct attention to understudied brain regions and neural circuits which may be important to study in OT experiments in humans anxiety disorders. Finally, we conclude by proposing questions and priorities for studying both the clinical potential of OT in anxiety, as well as mechanisms that may underlie this potential. Crucially, these priorities include targeted proof-of-concept clinical trials of IN OT in certain anxiety disorders, including investigations of individual moderators of OT's anxiolytic effects (i.e. sex, genetic factors, and early experience). This article is part of a Special Issue entitled Oxytocin and Social Behav.
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“These results are interesting in light of work showing that oxytocin can not only act as an anxiolytic,51, 52 but can also act as a painkiller.53”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [51]
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Metadata
- Authors
- MacDonald, K., & Feifel, D.
- Affiliations
- University of San Diego (US)
- Corresponding author
- MacDonald, Kai
- ORCID
- Feifel, David
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 1580
- Pages
- 22-56
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1968315111
- Cited by
- 139
- References
- 489
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 18 · 2020: 10 · 2019: 12 · 2018: 16 · 2017: 14 · 2016: 9 · 2015: 20 · 2014: 6
- FWCI
- 24.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, anxiety, anxiolytic effects, intranasal oxytocin, social attachment, anxiety disorders, evolutionary perspective, neuroimaging, genetic factors, sex differences, early life experience, treatment moderators, neural circuits
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Brain, Biological Evolution, Humans, Oxytocin
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