Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain
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Significance: Although understanding the precise nature of oxytocin’s influence on complex human social behavior has proven difficult, increasing evidence points to an anxiolytic effect. We use an imaging epigenetic approach to further parse oxytocin’s effects by examining a biological marker within the oxytocin system, DNA methylation of the oxytocin receptor gene ( OXTR ). Importantly, this epigenetic modification directly impacts the expression of oxytocin’s receptor, which is critical for the actions of oxytocin to have an effect. We find that higher levels of OXTR methylation are associated with increased neural response and decreased functional coupling within regions supporting social perception and emotion processing. This pattern of activity may be indicative of diminished emotion regulation to negative stimuli and increased risk of pathology.
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The STS result aligns with oxytocin increasing STS activity in autism and with OXTR methylation relating to STS activity.
“The current finding is consistent with a prior neuroimaging study demonstrating that oxytocin administration enhances STS activity in individuals with autism (37), and with a recent finding that OXTR methylation is associated with STS activity (6).”
From Epigenetic modification of <i>OXT</i> and human sociability (2016) · cites this paper as [6]
Methylation of OXTR in peripheral blood cells is associated with decreased correlated fluctuations in BOLD responses among limbic and cortical regions while viewing fearful and angry faces.
“Two studies have shown that naturally-occurring polymorphisms in human OXTR (the gene encoding OTR) are associated with correlated fluctuations in BOLD responses between hypothalamic, limbic, and/or cortical brain areas during social tasks (Tost et al., 2010; Tost et al., 2011), and one has shown that methylation of OXTR in peripheral blood cells is associated with decreased correlated fluct”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Puglia et al., 2015
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Early nurture epigenetically tunes the oxytocin receptor
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Oxytocin, vasopressin, and the motivational forces that drive social behaviors
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Overview of human oxytocin research
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Epigenetic modification of <i>OXT</i> and human sociability
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Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles
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- Authors
- Puglia, M. H., Lillard, T. S., Morris, J. P., & Connelly, J. J.
- Affiliations
- University of Oregon (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-02-09
- Volume
- 112
- Issue
- 11
- Pages
- 3308-3313
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4372000
- OpenAlex
- W2169807760
- Cited by
- 216
- References
- 78
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 6 · 2023: 15 · 2022: 9 · 2021: 19 · 2020: 35 · 2019: 16 · 2018: 27 · 2017: 26 · 2016: 27 · 2015: 17
- FWCI
- 52.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1228522)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor gene, oxytocin receptor, DNA methylation, epigenetic variation, emotional face processing, anger perception, fear perception, amygdala, fusiform gyrus, insula, emotion regulation, social cognition, individual differences
- MeSH terms
- Adult, Amygdala, Anger, Brain, Emotions, Face, Fear, Female, Humans, Male, Mental Processes, Nerve Net, Perception, Receptors, Oxytocin, DNA Methylation, Epigenesis, Genetic, Young Adult
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