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

2017 ◽  
Vol 114 (30) ◽  
pp. 8119-8124 ◽  
Author(s):  
Karen J. Parker ◽  
Ozge Oztan ◽  
Robin A. Libove ◽  
Raena D. Sumiyoshi ◽  
Lisa P. Jackson ◽  
...  
Keyword(s):  
Social Functioning ◽  
Placebo Treatment ◽  
Primary Outcome Measure ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Responsiveness ◽  
Social Deficits ◽  
Double Blind ◽  
Children With Asd ◽  
Social Abilities

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.

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

2019 ◽  
Vol 11 (491) ◽  
pp. eaau7356 ◽  
Author(s):  
Karen J. Parker ◽  
Ozge Oztan ◽  
Robin A. Libove ◽  
Noreen Mohsin ◽  
Debra S. Karhson ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Pilot Trial ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Responsiveness ◽  
Target Dose ◽  
Preclinical Research ◽  
Social Impairments ◽  
Children With Asd ◽  
The Social

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.

scholarly journals Infrequent intranasal oxytocin followed by positive social interaction improves symptoms in autistic children: a randomized clinical trial

2022 ◽  
Author(s):  
Jiao Le ◽  
Lan Zhang ◽  
Weihua Zhao ◽  
Siyu Zhu ◽  
Chunmei Lan ◽  
...  
Keyword(s):  
Social Interaction ◽  
Eye Tracking ◽  
Repetitive Behavior ◽  
Placebo Treatment ◽  
Autism Spectrum ◽  
Reliable Change Index ◽  
Autistic Children ◽  
Double Blind ◽  
Children With Asd ◽  
Positive Social Interaction

There are currently no approved drug interventions for social behavior dysfunction in autism spectrum disorder (ASD). Previous trials investigating effects of daily intranasal oxytocin treatment have reported inconsistent results and have not combined it with positive social interaction. However, In two preclinical studies we established that treatment every-other-day rather than daily is more efficacious in maintaining neural and behavioral effects by reducing receptor desensitization. We aimed to establish whether 6-weeks of intranasal oxytocin compared with placebo treatment, followed by a period of positive social interaction, would produce greater symptom improvements in children with ASD. A double-blind, randomized, cross over design trial was completed including 41 children with ASD aged 3-8 years. Primary outcomes were the Autism Diagnostic Observation Schedule-2 (ADOS-2) and social responsivity scale-2 (SRS-2). Secondary measures included other autism-related questionnaires and social attention assessed using two eye-tracking paradigms. A clinical reliable change index analysis revealed improvements in ADOS-2 total scores in 44% of children. Improvements in SRS-2 and behavioral adaptability scores were also found and correlated with increased basal saliva oxytocin concentrations. Additionally, oxytocin improved restrictive and repetitive behavior scores and increased time spent viewing dynamic social compared to geometric stimuli and the eye region of angry, happy and neutral expression faces. There were no adverse side-effects of oxytocin treatment. Overall, our results demonstrate that 6 weeks of intranasal oxytocin treatment administered every other day and followed by positive social interactions can improve clinical, eye-tracking and questionnaire-based assessments of symptoms in young autistic children.

The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Individual Characteristics ◽  
Receptive Vocabulary ◽  
Spectrum Disorder ◽  
School Age Children ◽  
Social Responsiveness ◽  
Contributing Factors ◽  
Children With Asd ◽  
Language Context

Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.

scholarly journals Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
J. Ellegood ◽  
S. P. Petkova ◽  
A. Kinman ◽  
L. R. Qiu ◽  
A. Adhikari ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Ex Vivo ◽  
Chromatin Modification ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Altered Expression ◽  
Developmental Growth ◽  
And Behavior

Abstract Background One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. Methods A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. Results We validated decreased Arid1b mRNA and protein in Arid1b+/− mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/− cerebellum. During neonatal development, Arid1b+/− mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/− mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/− mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male–female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/− mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. Limitations The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. Conclusions This study represents a full validation and investigation of a novel model of Arid1b+/− haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

scholarly journals Perceptions of Autism Spectrum Disorder (ASD) Etiology among Parents of Children with ASD

2021 ◽  
Vol 18 (13) ◽  
pp. 6774
Author(s):  
Wei-Ju Chen ◽  
Zihan Zhang ◽  
Haocen Wang ◽  
Tung-Sung Tseng ◽  
Ping Ma ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Content Analysis ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Parental Perceptions ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Structured Interviews ◽  
Children With Asd ◽  
Religious Factors

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted or repetitive behaviors. Parental perceptions of the etiology of their child’s ASD can affect provider–client relationships, bonding between parents and their children, and the prognosis, treatment, and management of children with ASD. Thus, this study sought to examine the perceptions of ASD etiology of parents of children with ASD. Methods: Forty-two parents of children diagnosed with ASD were recruited across Texas. Semi-structured interviews were conducted individually. All interviews were recorded and later transcribed verbatim for content analysis utilizing NVivo 12.0 (QSR International, Doncaster, Australia). Results: The content analysis identified the following themes regarding parental perceptions of ASD etiology: Genetic factors (40.5%), environmental factors (31.0%), problems that occurred during pregnancy or delivery (23.8%), vaccinations (16.7%), other health problems (7.1%), parental age at the time of pregnancy (4.8%), and spiritual or religious factors (2.4%). Conclusions: The parental perceptions of ASD etiology were diverse, but several views, such as vaccinations and spiritual or religious factors, were not based on scientific evidence. Health professionals and researchers can use these findings to develop and provide targeted education to parents who have children with ASD. Our findings also support policymakers in developing campaigns designed to increase parental ASD awareness and knowledge.

scholarly journals Sex differences in brain structure: An autism twin study on restricted and repetitive behaviors

2018 ◽  
Author(s):  
Annelies van’t Westeinde ◽  
Élodie Cauvet ◽  
Roberto Toro ◽  
Ralf Kuja-Halkola ◽  
Janina Neufeld ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Sex Differences ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Brain Anatomy ◽  
Social Responsiveness ◽  
Autism Symptoms ◽  
Twin Design ◽  
Restricted And Repetitive Behaviors

AbstractFemales with autism spectrum disorder have been reported to exhibit fewer and less severe restricted and repetitive behaviors and interests compared to males. This difference might indicate sex specific alterations of brain networks involved in autism symptom domains, especially within cortico-striatal and sensory integration networks. This study used a well-controlled twin design to examine sex differences in brain anatomy in relation to repetitive behaviors. In 75 twin pairs (n=150, 62 females, 88 males) enriched for autism spectrum disorder (n=32), and other neurodevelopmental disorders (n =32), we explored the association of restricted and repetitive behaviors and interests – operationalized by the Autism Diagnostic Interview-Revised (C domain) and the Social Responsiveness Scale-2 (Restricted Interests and Repetitive Behavior subscale), with cortical volume, surface area and thickness of neocortical, sub-cortical and cerebellar networks. Cotwin control analyses revealed within-pair associations between RRBI symptoms and the right intraparietal sulcus and right orbital gyrus in females only. These findings endorse the importance of investigating sex differences in the neurobiology of autism symptoms, and indicate different etiological pathways underlying restricted and repetitive behaviors and interests in females and males.

Aura

2018 ◽  
pp. 142-169 ◽  
Author(s):  
Marva Angélica Mora Lumbreras ◽  
Méndez-Trejo María de Lourdes ◽  
Sanluis-Ramírez Ariel
Keyword(s):  
Autism Spectrum Disorder ◽  
Augmented Reality ◽  
Nonverbal Communication ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Gps Data ◽  
Mobile Augmented Reality ◽  
Children With Asd ◽  
Augmented Reality Application ◽  
Age Range

A person with autism or autism spectrum disorder (ASD) presents conditions characterized by challenges with social skills, repetitive behaviors, speech, and nonverbal communication. Augmented reality (AR) combines reality with virtual aspects such as sound, video, graphics, or GPS data. Specifically, Aura is a mobile augmented reality application applied in the learning of children with ASD with the purpose of helping them in their relationships with the outside world and especially in their learning. Aura consists of five modules and 42 activities. The modules are Learn Basic Shapes, Repeat Basic Habits, Draw, Learn to Write, and Learn Values and Empathy. This project was tested by children of the Angelitos Mios Foundation, located in Apizaco Tlaxcala. The test showed favorable results. Tests were conducted with students in the age range of 4-8 years with ASD. The foundation is currently working on the acquisition of mobile devices for the implementation of Aura.

scholarly journals Risk Factors for Unhealthy Weight Gain and Obesity among Children with Autism Spectrum Disorder

2019 ◽  
Vol 20 (13) ◽  
pp. 3285 ◽  
Author(s):  
Khushmol K. Dhaliwal ◽  
Camila E. Orsso ◽  
Caroline Richard ◽  
Andrea M. Haqq ◽  
Lonnie Zwaigenbaum
Keyword(s):  
Risk Factors ◽  
Autism Spectrum Disorder ◽  
Weight Gain ◽  
Autism Spectrum ◽  
Lifestyle Factors ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Future Research ◽  
Children With Asd ◽  
Unhealthy Weight

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by social and communication deficits and repetitive behaviors. Children with ASD are also at a higher risk for developing overweight or obesity than children with typical development (TD). Childhood obesity has been associated with adverse health outcomes, including insulin resistance, diabetes, heart disease, and certain cancers. Importantly some key factors that play a mediating role in these higher rates of obesity include lifestyle factors and biological influences, as well as secondary comorbidities and medications. This review summarizes current knowledge about behavioral and lifestyle factors that could contribute to unhealthy weight gain in children with ASD, as well as the current state of knowledge of emerging risk factors such as the possible influence of sleep problems, the gut microbiome, endocrine influences and maternal metabolic disorders. We also discuss some of the clinical implications of these risk factors and areas for future research.

scholarly journals Machine Learning and Virtual Reality on Body Movements’ Behaviors to Classify Children with Autism Spectrum Disorder

2020 ◽  
Vol 9 (5) ◽  
pp. 1260 ◽  
Author(s):  
Mariano Alcañiz Raya ◽  
Javier Marín-Morales ◽  
Maria Eleonora Minissi ◽  
Gonzalo Teruel Garcia ◽  
Luis Abad ◽  
...  
Keyword(s):  
Machine Learning ◽  
Autism Spectrum Disorder ◽  
Virtual Reality ◽  
Quantitative Methods ◽  
Real Life ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Body Movements ◽  
Children With Asd

Autism spectrum disorder (ASD) is mostly diagnosed according to behavioral symptoms in sensory, social, and motor domains. Improper motor functioning, during diagnosis, involves the qualitative evaluation of stereotyped and repetitive behaviors, while quantitative methods that classify body movements’ frequencies of children with ASD are less addressed. Recent advances in neuroscience, technology, and data analysis techniques are improving the quantitative and ecological validity methods to measure specific functioning in ASD children. On one side, cutting-edge technologies, such as cameras, sensors, and virtual reality can accurately detect and classify behavioral biomarkers, as body movements in real-life simulations. On the other, machine-learning techniques are showing the potential for identifying and classifying patients’ subgroups. Starting from these premises, three real-simulated imitation tasks have been implemented in a virtual reality system whose aim is to investigate if machine-learning methods on movement features and frequency could be useful in discriminating ASD children from children with typical neurodevelopment. In this experiment, 24 children with ASD and 25 children with typical neurodevelopment participated in a multimodal virtual reality experience, and changes in their body movements were tracked by a depth sensor camera during the presentation of visual, auditive, and olfactive stimuli. The main results showed that ASD children presented larger body movements than TD children, and that head, trunk, and feet represent the maximum classification with an accuracy of 82.98%. Regarding stimuli, visual condition showed the highest accuracy (89.36%), followed by the visual-auditive stimuli (74.47%), and visual-auditive-olfactory stimuli (70.21%). Finally, the head showed the most consistent performance along with the stimuli, from 80.85% in visual to 89.36% in visual-auditive-olfactory condition. The findings showed the feasibility of applying machine learning and virtual reality to identify body movements’ biomarkers that could contribute to improving ASD diagnosis.

scholarly journals Efficacy and safety of memantine in children with autism spectrum disorder: Results from three phase 2 multicenter studies

Autism ◽  
2019 ◽  
Vol 23 (8) ◽  
pp. 2096-2111 ◽  
Author(s):  
Antonio Y Hardan ◽  
Robert L Hendren ◽  
Michael G Aman ◽  
Adelaide Robb ◽  
Raun D Melmed ◽  
...  
Keyword(s):  
Extended Release ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Social Responsiveness Scale ◽  
Social Responsiveness ◽  
Phase 2 ◽  
Open Label ◽  
Double Blind ◽  
Three Phase ◽  
Open Label Trial

Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori–defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.

Sign in / Sign up

Export Citation Format

Share Document