Common polymorphism in the oxytocin receptor gene ( OXTR ) is associated with human social recognition skills
Open accessAbstract
The neuropeptides oxytocin and vasopressin are evolutionarily conserved regulators of social perception and behavior. Evidence is building that they are critically involved in the development of social recognition skills within rodent species, primates, and humans. We investigated whether common polymorphisms in the genes encoding the oxytocin and vasopressin 1a receptors influence social memory for faces. Our sample comprised 198 families, from the United Kingdom and Finland, in whom a single child had been diagnosed with high-functioning autism. Previous research has shown that impaired social perception, characteristic of autism, extends to the first-degree relatives of autistic individuals, implying heritable risk. Assessments of face recognition memory, discrimination of facial emotions, and direction of gaze detection were standardized for age (7-60 y) and sex. A common SNP in the oxytocin receptor (rs237887) was strongly associated with recognition memory in combined probands, parents, and siblings after correction for multiple comparisons. Homozygotes for the ancestral A allele had impairments in the range -0.6 to -1.15 SD scores, irrespective of their diagnostic status. Our findings imply that a critical role for the oxytocin system in social recognition has been conserved across perceptual boundaries through evolution, from olfaction in rodents to visual memory in humans.
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Administration of synthetic oxytocin via nasal spray facilitates proactive social behaviors and increases eye gaze during social interaction.
“The importance of oxytocin for social interaction between humans is further substantiated by experiments showing that administration of synthetic oxytocin via nasal spray facilitates proactive social behaviors and increases, e.g., eye gaze during social interaction.”
From The Oxytocinergic System as a Mediator of Anti-stress and Instorative Effects Induced by Nature: The Calm and Connection Theory (2021) · cites this paper as Skuse et al., 2014
The Discussion (page not available) reports that exogenously administered oxytocin enhances recognition of facial information in humans, and a cited study in the References (page not available) reports increased gaze to the eye region of faces. Our copy does not say that administration was by nasal spray or that it facilitated proactive social behaviors; it also does not establish increased eye gaze during social interaction specifically. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAdministration of oxytocin increases an individual's ability to interpret other individuals' facial language and tone of voice, as well as body language.
“Moreover, administration of oxytocin increases an individual’s ability to interpret other individuals’ facial language and tone of voice (Hollander et al., 2003, 2007; Domes et al., 2014; Skuse et al., 2014), as well as body language (Kéri and Benedek, 2009).”
From The Oxytocinergic System as a Mediator of Anti-stress and Instorative Effects Induced by Nature: The Calm and Connection Theory (2021) · cites this paper as Skuse et al., 2014
The Discussion (page not provided) says that administered oxytocin enhances recognition of facial information in humans. It does not establish improved interpretation of tone of voice, or specifically of facial expressions. The citing sentence attributes the separate body-language claim to Kéri and Benedek, not to Skuse. (LLM, conf=0.85)
Experimental — accuracy not yet measuredNoncoding SNPs in the human OXTR are associated with pair bonding, parenting, face recognition, and autism.
“Single nucleotide polymorphisms (SNPs) in noncoding regions of the human OXTR have been associated with pair bonding behaviors (19), parenting (1), face recognition skills (20), and autism (21).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [20]
The sequence containing NT213739 overlapped peaks of DNase hypersensitivity and CTCF binding within the large intron, a region proposed to contain cis-regulatory elements in humans.
“The sequence containing NT213739 overlapped peaks of DNase hypersensitivity and CTCF binding within the large intron, a region proposed to contain cis-REs in humans (20, 61, 62).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [20]
Within the third intron of human OXTR, a CTCF peak is close to SNP rs237887, predicted to lie near a cis-regulatory element and linked to face recognition and ASD diagnosis.
“In the human OXTR third intron, the CTCF peak is found near a SNP, rs237887, that was predicted to be near a cis-RE, and associated with face recognition abilities (20) and ASD diagnosis (21).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [20]
CTCF binding peaks occur in the intron and near the promoter of both mouse Oxtr and human OXTR.
“as CTCF binding peaks are found in the intron as well as near the promoter of both the mouse Oxtr (Figure 3b) and human OXTR (20).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [20]
Other studies report links between OXTR and ASD endophenotypes, such as structural differences in social-cognition brain regions.
“and others have reported associations with endophenotypes of ASD (20, 82, 83), including structural variability in brain regions relevant to social cognition (80, 84).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [20]
Polymorphisms in the human OTR predict social behavioral phenotypes, including those associated with autism, and how early-life experiences shape later psychiatric outcomes.
“Several psychiatric genetic studies have suggested that polymorphisms in the human OTR predict not only social behavioral phenotypes, including those associated with autism (Skuse et al. 2014; Parker et al. 2014; LoParo and Waldman 2015), but also how early-life experiences shape later psychiatric outcomes”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Skuse et al. 2014
Abnormalities in emotion recognition are central to several psychiatric conditions including ASD, in which OTR polymorphisms and insular cortex hypofunction are correlates of symptom severity.
“Abnormalities in emotion recognition are central to several psychiatric conditions including ASD47,48, in which OTR polymorphisms49,50 and insular cortex hypofunction8,9 are correlates of symptom severity.”
From Insular cortex mediates approach and avoidance responses to social affective stimuli (2018) · cites this paper as [50]
Emotion discrimination abilities in mice are dependent on the OXT system.
“we have demonstrated that emotion discrimination abilities in mice are dependent on the OXT system”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [10]
OXT has been associated with social cognitive functions, such as emotion recognition in humans.
“OXT has been associated with social cognitive functions, such as emotion recognition [8-10, 33-36, 38, 39].”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [10]
Single nucleotide polymorphisms in OXTR are associated with impaired social memory.
“Single nucleotide polymorphisms in OXTR are associated with impaired social memory [32]”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [32]
Genetic variation in human OXTR contributes to variation in behavior.
“Similar to findings in prairie voles, multiple studies suggest that genetic variation in human OXTR contributes to variation in behavior.”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [32]
SNP rs237887 is strongly associated with recognition memory in individuals with ASD, their parents, and their siblings.
“Importantly, one of these SNPs (rs237887) was found to be strongly associated with recognition memory in individuals with ASD, their parents, and their siblings (Skuse et al. 2014), suggesting a critical role of the OT system in social recognition.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Skuse et al. 2014
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“In the human OXTR third intron, the CTCF peak is found near a SNP, rs237887, that was predicted to be near a cis-RE and associated with face recognition abilities (20) and ASD diagnosis (21).”
InfluentialSelf-citationYoung, L. J., & Barrett, C. E. (2015) · Science · doi:10.1126/science.aaa8120 · Cited by 200 · see citing works
Self-citationFreeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.023 · Cited by 185 · see citing works
“Genetic studies also suggest that the OT receptor (OXTR) plays some role in face and emotion recognition and pair bonding behaviors in humans (Skuse et al., 2013; Walum et al., 2012).”
BackgroundJohnson, Z. V., Walum, H., Jamal, Y. A., Xiao, Y., Keebaugh, A. C., Inoue, K., & Young, L. J. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.11.011 · Cited by 190 · see citing works
Self-citationNeurobiological mechanisms of social attachment and pair bonding
Johnson, Z. V., & Young, L. J. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.01.009 · Cited by 169 · see citing works
Self-citationOxytocin and Social Relationships: From Attachment to Bond Disruption
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Oxytocin, vasopressin, and the motivational forces that drive social behaviors
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Self-citationAoki, Y., Watanabe, T., Abe, O., Kuwabara, H., Yahata, N., Takano, Y., Iwashiro, N., Natsubori, T., Takao, H., Kawakubo, Y., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.74 · Cited by 95 · see citing works
Epigenetic modification of <i>OXT</i> and human sociability
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Self-citationOxytocin, social cognition and psychiatry
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Self-citationAdaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder
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Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
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Self-citationA precision medicine approach to oxytocin trials
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Self-citationOxytocin, vasopressin and social behavior in the age of genome editing: a comparative perspective
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Self-citationBridging the gap between rodents and humans: The role of non‐human primates in oxytocin research
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Evolutionary diversity as a catalyst for biological discovery
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Self-citationNovel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals
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- Authors
- Skuse, D. H., Lori, A., Cubells, J. F., Lee, I., Conneely, K. N., Puura, K., Lehtimäki, T., Binder, E. B., & Young, L. J.
- Affiliations
- National Health Service (GB)
- Departments of cHuman Genetics and
- University College London (GB)
- Fimlab (Finland) (FI)
- Tampere University Hospital (FI)
- Max Planck Institute of Psychiatry (DE)
- Emory University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-12-23
- Volume
- 111
- Issue
- 5
- Pages
- 1987-1992
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3918840
- OpenAlex
- W2014069837
- Cited by
- 207
- References
- 60
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 3 · 2023: 8 · 2022: 14 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 40 · 2017: 20 · 2016: 29 · 2015: 27 · 2014: 20
- FWCI
- 37.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (P51OD011132)
- National Institute of Mental Health (K02MH064692, MH064692, R29MH056897, MH056897, P50MH100023, R01MH056897)
- National Center for Research Resources (P51RR165)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- oxytocin receptor, vasopressin 1a receptor, oxytocin, vasopressin, social recognition, face memory, autism spectrum disorder, high-functioning autism, first-degree relatives, single nucleotide polymorphisms, gaze direction detection, social memory, genetic association
- MeSH terms
- Adolescent, Adult, Alleles, Child, Child Development Disorders, Pervasive, Child, Preschool, Cognition, Female, Fixation, Ocular, Humans, Male, Memory, Middle Aged, Social Behavior, Receptors, Vasopressin, Receptors, Oxytocin, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Recognition, Psychology, Young Adult, Genetic Loci, Genetic Association Studies, Endophenotypes
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