Cerebrospinal fluid vasopressin and symptom severity in children with autism

Oztan, Ozge; Garner, Joseph P.; Partap, Sonia; Sherr, Elliott H.; Hardan, Antonio Y.; Farmer, Cristan; Thurm, Audrey; Swedo, Susan E.; Parker, Karen J.

doi:10.1002/ana.25314

Cited by 42 publications

(36 citation statements)

References 21 publications

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“…We have also documented that low-social compared to high-social monkeys exhibit lower concentrations of the "social" neuropeptide arginine vasopressin in cerebrospinal fluid [Parker et al, 2018]. Importantly, we have forward translated this biomarker finding to three cohorts of ASD patients [Oztan et al, 2018;Oztan et al, 2020;Parker et al, 2018]. Here, we reverse translated the SRS to our macaque model and showed that low-social vs. high-social monkeys exhibit greater social impairments on an instrument used in humans to screen for ASD.…”

Section: Discussionmentioning

confidence: 95%

A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population

et al. 2020

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Naturally low‐social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low‐social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD screening tool. We performed quantitative social behavior assessments and mSRS ratings on a total of N = 349 rhesus macaques (Macaca mulatta) housed in large, outdoor corrals. In one cohort (N = 116), we conducted inter‐rater and test‐retest reliabilities, and in a second cohort (N = 233), we evaluated the convergent construct and predictive validity of the mSRS‐Revised (mSRS‐R). Only 17 of the original 36 items demonstrated inter‐rater and test–retest reliability, resulting in the 17‐item mSRS‐R. The mSRS‐R showed strong validity: mSRS‐R scores robustly predicted monkeys' social behavior frequencies in home corrals. Monkeys that scored 1.5 standard deviations from the mean on nonsocial behavior likewise exhibited significantly more autistic‐like traits, and mSRS‐R scores predicted individuals' social classification (low‐social vs. high‐social) with 96% accuracy (likelihood ratio chi‐square = 25.07; P < 0.0001). These findings indicate that the mSRS‐R is a reliable, valid, and sensitive measure of social functioning, and like the human SRS, can be used as a high‐throughput screening tool to identify socially impaired individuals in the general population. Lay Summary Variation in autistic traits can be measured in humans using the Social Responsiveness Scale (SRS). Here, we revised this scale for rhesus macaques (i.e., the mSRS‐R), and showed that macaques exhibit individual differences in mSRS‐R scores, and at the behavioral extremes, low‐social vs. high‐social monkeys exhibit more autistic‐like traits. These results suggest that the mSRS‐R can be used as a screening tool to rapidly and accurately identify low‐social monkeys in the general population. Autism Res 2020, 13: 1465–1475. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 95%

A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population

et al. 2020

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“…We found that participants with the highest pretreatment AVP concentrations in blood benefitted the most from intranasal AVP treatment. This finding may seem counterintuitive, particularly in light of our recent studies showing that low AVP concentrations in CSF could be used to differentiate ASD cases from non-ASD control individuals (13,14). One might therefore expect that it would be those children with the lowest endogenous AVP concentrations that stood to benefit the most from intranasal AVP treatment.…”

Section: Discussionmentioning

confidence: 97%

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

et al. 2019

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The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial’s primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F1,20 = 9.853; P = 0.0052; ηp2 = 33.0%; Cohen’s d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

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“…In male children with ASD, lower VP concentration in the CSF predicts greater social impairments (Oztan et al, 2018). In a recent phase 2 clinical trial, intranasal VP administration improved the primary outcome measure of social abilities and diminished anxiety symptoms in children with ASD (Parker et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Vasopressin Signaling Buffers Stress-Dependent Synaptic Changes in Female Mice

2020

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In many species, social networks provide benefit for both the individual and the collective. In addition to transmitting information to others, social networks provide an emotional buffer for distressed individuals. Our understanding about the cellular mechanisms that contribute to buffering is poor. Stress has consequences for the entire organism, including a robust change in synaptic plasticity at glutamate synapses onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). In females, however, this stress-induced metaplasticity is buffered by the presence of a naïve partner. This buffering may be due to discrete behavioral interactions, signals in the context in which the interaction occurs (i.e. olfactory cues), or it may be influenced by local signaling events in the PVN. Here, we show that local vasopressin (VP) signaling in PVN buffers the short-term potentiation (STP) at glutamate synapses after stress. This social buffering of metaplasticity, which requires the presence of another individual, was prevented by pharmacological inhibition of the VP 1a receptor in female mice. Exogenous VP mimicked the effects of social buffering and reduced STP in CRH PVN neurons from females but not males. These findings implicate VP as a potential mediator of social buffering in female mice.

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Cerebrospinal fluid vasopressin and symptom severity in children with autism

Cited by 42 publications

References 21 publications

A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population

A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

Sex-Specific Vasopressin Signaling Buffers Stress-Dependent Synaptic Changes in Female Mice

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