An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism

Méziane, Hamid; Schaller, Fabienne; Bauer, Štefan; Villard, Claude; Matarazzo, Valéry; Riet, Fabrice; Guillon, Gilles; Lafitte, Daniel; Desarménien, Michel G.; Tauber, Maïthé; Muscatelli, Françoise

doi:10.1016/j.biopsych.2014.11.010

Cited by 149 publications

(189 citation statements)

References 47 publications

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“…Despite preclinical evidence indicating that OXT may be a promising therapeutic for human social impairments, prior intranasal OXT treatment trial findings for ASD have been equivocal; some trials have reported that OXT improves social abilities (19,20), but other trials have not (21,22). However, the preponderance of preclinical evidence demonstrating OXT rescue of social phenotypes has been gleaned from animals with known OXT signaling impairments (13,15). Because idiopathic ASD is characterized by enormous heterogeneity, including substantial variability in blood OXT concentrations (27), we hypothesized that the prior ambiguous OXT clinical trial findings might be attributable, at least in part, to variability in participants' pretreatment neuropeptide biology.…”

Section: Discussionmentioning

confidence: 97%

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

Parker

Oztan

Libove

et al. 2017

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

277

256

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Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.A utism spectrum disorder (ASD) is a brain disorder of early childhood onset. ASD is characterized by core social communication impairments as well as restricted, repetitive behaviors, which jeopardize the development of appropriate social skills and the maintenance of social relationships (1). Despite being one of the most devastating childhood disorders in terms of prevalence [1 in 68 US children (2)] and societal cost [$236 billion expended annually in the United States (3)], ASD pathophysiology remains poorly understood. Consequently, there are no approved medications that enhance social abilities in individuals with ASD.

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Section: Discussionmentioning

confidence: 97%

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

Parker

Oztan

Libove

et al. 2017

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

277

256

View full text Add to dashboard Cite

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“…Nevertheless, in preclinical animal models characterized by autistic-like symptoms, OT administration has been reported to rescue social deficits when given just after birth or in the first postnatal days (74)(75)(76)(77)(78) or in young adults (79)(80)(81). Notably, in some of the animal models in which the OT treatment was successful, a dysregulation of the OT/OTR system was concomitantly reported.…”

Section: As a Conclusion: Ot Signaling And Psychosocial Alterationsmentioning

confidence: 93%

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain

Grinevich

Knobloch‐Bollmann

Eliava

et al. 2016

Biological Psychiatry

243

187

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Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases.

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“…A higher OXT content in the hypothalamus has been reported in BTBR mice, a validated model of ASD [12]. Cntnap2 (contactin-associated proteinlike 2) gene-knockout mice display autistic-like behaviors, and have reduced OXT expression in the PVN and an overall reduction in brain OXT levels [13], while exogenous OXT treatment partially restores normal function of the OXT system and leads to improved social behaviors [13,14]. Human studies have focused on pharmacological administration and the measurement of plasma neuropeptides, mainly of OXT.…”

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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An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism

Cited by 149 publications

References 47 publications

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain

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

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