The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

Yatawara, Chathuri; Einfeld, Stewart; Hickie, Ian B.; Davenport, Tracey A; Guastella, Adam J.

doi:10.1038/mp.2015.162

Cited by 282 publications

(296 citation statements)

References 37 publications

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“…Human studies have focused on pharmacological administration and the measurement of plasma neuropeptides, mainly of OXT. It has been suggested that intranasal OXT is beneficial for the remission of autistic symptoms by improving cooperation and sense of trust [15] as well as by enhancing social responsiveness [16] and social reciprocity [17].…”

Section: Introductionmentioning

confidence: 99%

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Zhang

Dai

et al. 2016

Neurosci. Bull.

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Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ''twin'' nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

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Section: Introductionmentioning

confidence: 99%

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Zhang

Dai

et al. 2016

Neurosci. Bull.

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“…Clinical trials of OT in autistic patients are ongoing, yet several studies have produced inconclusive results (4)(5)(6)(7)(8), demanding improvements to the efficacy and reliability of OT-based therapeutics. One strategy is to take advantage of existing physiological pathways in the brain that regulate OT activity to combinatorially enhance the oxytocinergic effects on social functions.…”

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confidence: 99%

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Monte

Piva

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt. Furthermore, attention to various facial regions was differentially modulated depending on social context. Using the Allen Institute's transcriptional atlas, we further established the colocalization of μ-opioid and κ-opioid receptor genes and OT genes at the OT-releasing sites in the human brain. These data across monkeys and humans support a regulatory relationship between the OT and opioid systems and suggest that administering OT under opioid antagonism may boost the therapeutic efficacy of OT for enhancing social cognition.T he efficacy of oxytocin (OT) in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability (1-3). Clinical trials of OT in autistic patients are ongoing, yet several studies have produced inconclusive results (4-8), demanding improvements to the efficacy and reliability of OT-based therapeutics. One strategy is to take advantage of existing physiological pathways in the brain that regulate OT activity to combinatorially enhance the oxytocinergic effects on social functions. In this regard, a promising candidate is the opioid system.In addition to the evolutionarily conserved OT system (9), the opioid system has been implicated in regulating social behavior. Excessive opioid activity in the brain has been discussed with respect to the development of early childhood autism (10). Abnormalities in central opioid levels have been observed in some individuals with autism, and clinical trials with predominantly μ-opioid blockers, such as naltrexone or naloxone (NAL), have yielded promising results in ameliorating both social and nonsocial deficits (11). Specifically, μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain (12) and are strongly expressed in reward-related regions of the primate brain (13). In rhesus macaques, carrying the G allele of the μ-opioid receptor gene OPRM1, compared with homozygous C alleles, is associated with stronger maternal attachment in infants (14) and more effective prevention of infant separation in mothers (15). Additionally, opioid agonists, such as morphine, decrease physical contact between social partners, whereas NAL administration increases solicitation for social contact, such as grooming and proximity (16)(17)(18)(19).The physiological relationship between the opi...

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“…Although seeing improvement in specific social behaviors inside a laboratory is an important first step, research also needs to demonstrate that oxytocin nasal spray can improve day-to-day social functioning in the real world, with long-term daily use. Early research has shown that taking oxytocin nasal spray over 5 weeks led to small improvements in social behavior in young children with ASC [5]. However, other research in older children and adults with ASC has not shown any improvements after similar periods of taking oxytocin.…”

Section: Oxytocin As a Treatment?mentioning

confidence: 99%

Oxytocin: How Does This Neuropeptide Change Our Social Behavior?

Quintana¹,

Alvares²

2016

Front. Young Minds.

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Neuropeptides are small molecules that act as messengers between different brain regions. There are roughly 100 neuropeptides that are important for various functions, including hunger, memory, and learning. Oxytocin is a neuropeptide that plays a crucial role in childbirth and breastfeeding. More recently, oxytocin has been shown to be essential for our social behaviors. When given to people in the form of a nasal spray, oxytocin can change key aspects of social behavior, such as how easily we can recognize emotions in others. People with autism often have difficulties in understanding and using social information, and scientists have been testing oxytocin nasal spray as a potential treatment. But how does oxytocin nasal spray travel from the nose to the brain, and how does it change how we behave socially?Neuropeptides are small molecules that act as messengers between different brain regions. There are roughly 100 neuropeptides that control various functions, including hunger, memory, and learning. Oxytocin is a neuropeptide that plays a crucial role in childbirth and breastfeeding. Oxytocin is produced in the hypothalamus, an almond-sized structure near the base of our brain. After production, oxytocin moves from the hypothalamus to the Neuropeptide A small molecule naturally produced in the body that acts a messenger to trigger responses in our body, such as the feeling of hunger. OxytocinA neuropeptide (see above) that is known to influence how we behave around other people.

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The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

Cited by 282 publications

References 37 publications

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

Oxytocin: How Does This Neuropeptide Change Our Social Behavior?

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