Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders

Francis, Sunday M.; Sagar, Angela; Levin-Decanini, Tal; Liu, W.; Carter, C.S.; Jacob, Suma

doi:10.1016/j.brainres.2014.01.021

Cited by 86 publications

(57 citation statements)

References 195 publications

(259 reference statements)

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“…Another reason could be due to dysregulation of oxytocin (OT) and arginine vasopressin (AVP) in the brain. The dysregulation of the OT system in animals and humans is linked with marked deficits in social behavior and anxiety (24). There is a scarcity of OT producing neurons in the paraventricular nucleus of the hypothalamus (PVN) in individuals with PWS (25) and in the Fmr1 KO (knock-out) mice (24).…”

Section: Neurobiology Of Fxs With Pwpmentioning

confidence: 99%

“…The dysregulation of the OT system in animals and humans is linked with marked deficits in social behavior and anxiety (24). There is a scarcity of OT producing neurons in the paraventricular nucleus of the hypothalamus (PVN) in individuals with PWS (25) and in the Fmr1 KO (knock-out) mice (24). OT administration increases trust and diminishes disruptive behavior in individuals with PWS (26); in those with FXS OT therapy improves social anxiety (27).…”

Section: Neurobiology Of Fxs With Pwpmentioning

confidence: 99%

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The neurobiology of the Prader-Willi phenotype of fragile X syndrome

Muzar

Lozano

Kolevzon

et al. 2016

IRDR

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Section: Neurobiology Of Fxs With Pwpmentioning

confidence: 99%

Section: Neurobiology Of Fxs With Pwpmentioning

confidence: 99%

The neurobiology of the Prader-Willi phenotype of fragile X syndrome

Muzar

Lozano

Kolevzon

et al. 2016

IRDR

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“…Studies of rodent models of human syndromes with high ASD penetrance (e.g., fragile-X syndrome, Prader-Willi syndrome, cortical dysplasia, and focal epilepsy syndrome modeled using CNTNAP2-knockout mice) have reported social impairments and diminished numbers of hypothalamic OXT-producing cells (12)(13)(14). This reduction in brain OXT has been associated with lower blood OXT concentrations in transgenic vs. wild-type animals, with social impairments ameliorated in transgenic animals following OXT treatment (13,15).…”

mentioning

confidence: 99%

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.

278

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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“…We approximated the dose of the drug based on prior studies [57], and in our experiments at least one-tenth of the effective dose did not modify the effects of ECT at all. Still, the involvement of vasopressin receptors cannot be discounted, particularly considering that vasopressin has been implicated in regulating social behaviors and mechanisms of autism [58,59]. A more definitive answer could be obtained from the examination of autism in oxytocin and/or oxytocin knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

et al. 2015

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Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino--(methylsulfonyl)butanamide hydrochloride abolished ECTinduced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

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Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders

Cited by 86 publications

References 195 publications

The neurobiology of the Prader-Willi phenotype of fragile X syndrome

The neurobiology of the Prader-Willi phenotype of fragile X syndrome

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

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

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