Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Open accessAbstract
Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.
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Animal model research points to a strong relationship between socially monogamous attachment behaviors and the expression of oxytocin within the brain, along with vasopressin and dopamine.
“Animal model research points to a strong relationship between socially monogamous attachment behaviors and the expression of oxytocin within the brain—along with that of an affiliated peptide, vasopressin, and a suite of auxiliary hormones and neurotransmitters including dopamine.”
From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [37]
The Discussion (page not available) reports that animal studies show oxytocin promotes social bonding behavior. It does not specify socially monogamous attachment or link that behavior to vasopressin and dopamine; vasopressin appears in reference titles, but those titles do not establish the claimed relationship. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral trials have shown that a single dose of intranasal oxytocin enhanced performance on measures of social cognition or motivation, compared with placebo, in persons with autism spectrum disorder.
“Several trials have shown that a single dose of intranasal oxytocin enhanced performance on measures of social cognition10,11 or motivation,12–14 as compared with placebo, in persons with autism spectrum disorder.”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [13]
Infusing oxytocin into the brains of female prairie voles and vasopressin into the brains of male prairie voles significantly enhanced pair-bonding even in the absence of actual mating.
“Infusing oxytocin into the brains of the females, and vasopressin into the brains of the males, significantly enhanced pair-bonding even in the absence of actual mating.”
From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [37]
The Discussion says generally that animal studies show oxytocin promotes social bonding, but it does not describe prairie voles or pair-bonding without mating. A search for female and male prairie voles, vasopressin, infusion, and mating found no passage reporting the claimed experiment or result. (LLM, conf=0.74)
Experimental — accuracy not yet measuredIntranasal oxytocin acutely increases gaze to the eye region of human faces in autistic populations.
“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [65]
In ASD research, improved facial emotion recognition is partly due to more time spent looking at the eye area.
“within the ASD literature there is evidence that improved facial emotion recognition is due, in part, to participants spending more time looking at the eye area of faces (e.g., Andari et al., 2010).”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Andari et al., 2010
The present results agree with autism-spectrum-disorder literature indicating that oxytocin raises attention to socially relevant stimuli, particularly the eye region.
“Nevertheless, our results are consistent with evidence from ASD literature suggesting that OXT increases attention to socially relevant stimuli, and specifically for the eye-region (e.g., Andari et al., 2010).”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Andari et al., 2010
Plasma oxytocin is significantly elevated 10 minutes after intranasal oxytocin administration.
“A second study [16] also found significantly elevated plasma OT concentrations at 10 minutes post-administration.”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [16]
Enhanced prosocial effects of intranasally administered OT are especially pronounced for individuals with socio-emotional deficits, such as Asperger syndrome or high alexithymia.
“It appears that the enhanced prosocial effects of intranasally administered OT are especially pronounced for individuals suffering from socio-emotional deficits, as is the case for individuals with Asperger syndrome (Andari et al., 2010) or high alexithymia (Luminet et al., 2011).”
From The effect of oxytocin on cooperation in a prisoner's dilemma depends on the social context and a person's social value orientation (2014) · cites this paper as Andari et al., 2010
In individuals with autism, intranasal oxytocin increases emotion recognition and feelings of trust and willingness to interact socially.
“In individuals with autism, intranasal OT was shown to increase emotion recognition (13) and to increase feelings of trust and willingness to interact socially (16).”
From Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles (2013) · cites this paper as [16]
Oxytocin administration has been shown to improve social decision-making in patients with autism.
“OT administration has been shown to improve social decision-making (Andari et al., 2010; Hollander et al., 2007)”
From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Andari et al., 2010
Oxytocin administration has been shown to promote visual scanning of faces in patients with autism.
“promote visual scanning of faces (Andari et al., 2010)”
From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Andari et al., 2010
Similar doses of oxytocin have been administered to subjects in previous studies of social functioning.
“Similar doses of OT have been administered to subjects in previous studies of social functioning (Andari et al., 2010; Feifel et al., 2010; Guastella et al., 2008; Hollander et al., 2007; Ditzen et al., 2009).”
From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Andari et al., 2010
Previous studies have employed simulated social games and static social photographs to evaluate the effects of oxytocin on social behaviors.
“Previous studies have employed simulated social games (Andari et al., 2010; Kosfeld et al., 2005), and static social photographs (Guastella et al., 2008) to evaluate the effects of OT on social behaviors.”
From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Andari et al., 2010
The effect of oxytocin on cooperative behavior depends on characteristics of the individual.
“Other research suggests that the effect of oxytocin on cooperative behavior depends on characteristics of the individual (Andari et al. 2010; Bartz et al. 2010a; Bartz et al. 2011).”
From Acute intranasal oxytocin improves positive self-perceptions of personality (2012) · cites this paper as Andari et al. 2010
Oxytocin has been shown to increase gazing time on the eye region, and to improve performance on the Reading the Mind in the Eyes Task in adults and adolescents with ASD.
“For example, oxytocin has been shown to increase gazing time on the eye region33, and to improve performance on the Reading the Mind in the Eyes Task in adults and adolescents with ASD48,49.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [33]
In subjects diagnosed with autism, a single intranasal administration of OXT might improve, at least temporarily, emotion recognition abilities in the Reading the Mind in the Eyes test and the patients' ability to process socially relevant cues in a computer-based game.
“Moreover, in subjects diagnosed with autism, a single intranasal administration of OXT might be able to improve, at least temporarily, emotion recognition abilities in the Reading the Mind in the Eyes test and the patients' ability to process socially relevant cues in a computer-based game (Andari et al, 2010;Green and Hollander, 2010;Guastella et al, 2010).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Andari et al, 2010
Most randomized clinical trials have found some oxytocin effects on ASD symptoms and brain function, but not all trials have reported effects.
“While most randomized clinical trials have found some oxytocin effects on ASD symptoms33,50–52 and brain function50–52,80,81, not all trials have reported effects82.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [33]
OT plasma concentration is significantly lower in patients with ASD than in healthy subjects.
“Studies in our lab and others have found that OT plasma concentration is significantly lower in patients with ASD than in healthy subjects (Andari et al. 2010; Modahl et al. 1998).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Andari et al. 2010
Intranasal administration (24 IU) of OT to adults with ASD (men between 18 and 45 years old) enhanced their attention to faces and improved social recognition of implicit cues within an interactive social game in a within-subject placebo-controlled study.
“In terms of exogenous effects of OT, we showed that intranasal administration (24 IU) of OT to adults with ASD (men between 18 and 45 years old) enhanced their attention to faces and improved the social recognition of implicit cues within an interactive social game in a within subject placebo-controlled study (Andari et al. 2010).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Andari et al. 2010
Intranasal OT increases attention to the eyes in individuals with social deficits, such as autism.
“Intranasal OT also increases attention to the eyes in individuals with social deficits. Individuals with autism, for example, spend more time attending to the eye region of faces following intranasal OT compared to placebo (Andari et al., 2010).”
From Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology (2014) · cites this paper as Andari et al., 2010
Lower average blood plasma oxytocin concentrations are found in individuals with ASD relative to controls.
“two studies have found lower average levels of blood plasma concentrations of oxytocin in individuals with ASD relative to controls [166,167]”
From Social “wanting” dysfunction in autism: neurobiological underpinnings and treatment implications (2012) · cites this paper as [166]
Oxytocin, relative to placebo, increases cooperative behaviors, trust, and attention to socially informative stimuli (e.g., eyes) in individuals with ASD.
“increases cooperative behaviors, trust, and attention to socially informative stimuli (for example, eyes) [166]”
From Social “wanting” dysfunction in autism: neurobiological underpinnings and treatment implications (2012) · cites this paper as [166]
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Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin
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BackgroundProsocial effects of oxytocin and clinical evidence for its therapeutic potential
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Immunohistochemical localization of oxytocin receptors in human brain
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“every study examining the effects of exogenous oxytocin on social cognition and behavior in normal and clinical populations have made use of the intranasal delivery route (Andari et al., 2010; Domes et al., 2007; Guastella et al., 2008; Kosfeld et al., 2005).”
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Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder
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The cross-generation transmission of oxytocin in humans
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The Role of Oxytocin in Human Affect: A Novel Hypothesis
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Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism
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Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models
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The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies
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Variation in the Oxytocin Receptor Gene Is Associated with Pair-Bonding and Social Behavior
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“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
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Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience
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“spectrum disorder (ASD) and schizophrenia (12-17), and one report suggests that OXTR expression may be reduced in ASD (18).”
Chronic and acute intranasal oxytocin produce divergent social effects in mice
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Intranasal oxytocin blocks alcohol withdrawal in human subjects
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“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”
BackgroundOxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism
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Switching brain serotonin with oxytocin
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Oxytocin, cortisol, and triadic family interactions
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Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis
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“…Rutigliano et al. / Psychiatry Research 241 (2016) 207–220 217 domains, namely emotion recognition (Guastella et al., 2010a), social cognition (Andari et al., 2010), and core autistic repetitive behaviours (e.g. ordering, compulsion to tell/ask and touching) (Hollander et al., 2003), to…”
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Optogenetic insights on the relationship between anxiety-related behaviors and social deficits
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Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome
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Frontotemporal Lobar Degeneration: Epidemiology, Pathology, Diagnosis and Management
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Oxytocin blunts social vigilance in the rhesus macaque
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Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
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Oxytocin, vasopressin, and the motivational forces that drive social behaviors
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Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques
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Intranasal oxytocin selectively attenuates rhesus monkeys’ attention to negative facial expressions
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- Authors
- Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Centre de Neuroscience Cognitive, Unité Mixte de Recherche 5229, Centre National de la Recherche Scientifique, 69675 Bron, France; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-02-16
- Volume
- 107
- Issue
- 9
- Pages
- 4389-4394
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2840168
- OpenAlex
- W2034453108
- Cited by
- 941
- References
- 32
- Citations by year
- 2026: 16 · 2025: 14 · 2024: 25 · 2023: 44 · 2022: 37 · 2021: 44 · 2020: 91 · 2019: 48 · 2018: 51 · 2017: 72 · 2016: 68 · 2015: 81 · 2014: 100 · 2013: 89 · 2012: 74
- FWCI
- 109.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation FondaMental
- Fondation Orange
- Institut National de la Santé et de la Recherche Médicale
- Fondation de France
- Centre National de la Recherche Scientifique
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Social Psychology › Action Observation and Synchronization
- Keywords
- oxytocin, autism spectrum disorder, Asperger syndrome, social behavior, social cognition, trust, gaze behavior, face processing, social interaction, social dysfunction
- MeSH terms
- Administration, Inhalation, Adolescent, Adult, Autistic Disorder, Emotions, Female, Humans, Male, Oxytocin, Social Behavior, Young Adult
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