Autism Diagnostic Observation Scale Research Articles

Novel Insights into Obesity in Preschool Children with Autism Spectrum Disorder.

Obesity is present in 8-32% of the children with Autism Spectrum Disorder (ASD). However, most studies are performed in school-aged children from the USA. The current study compares obesity rates of Dutch preschoolers with ASD with children from the Dutch general population and explores which child- and parental factors are related to obesity in children with ASD. This cross-sectional study is part of the ongoing Tandem Study (Dutch Trial register: NL7534). Seventy-eight children with ASD aged 3-7 years and their parents (77 mothers, 67 fathers) participated. Child factors are: Body Mass Index (by physical measurement), child eating behavior (Child Eating Behavior Questionnaire), child problem behavior (Child Behavior Checklist), and ASD severity (Autism Diagnostic Observation Scale 2). Parental factors are: BMI (by physical measurement), parental eating behavior (Dutch Eating Behavior Inventory), parenting stress (The Parenting Stress Questionnaire) and highest completed educational level (SES). Children with ASD were 8 times more often obese (16.8%) than children from the general population (2.0%). Child BMI correlated positively with child food approach behavior and maternal BMI, and correlated negatively with child 'Slowness in eating'. There was no correlation between child BMI and ASD severity, problem behavior, parental eating behavior, parental stress and SES. Thus, Dutch, preschool children with ASD have 8 times higher obesity rates than children from the general population. More attention to obesity risk in research and clinical care could contribute to the quality of life of individuals with ASD and their families. CLINICAL TRIAL REGISTRATION: Dutch Trial register, NL7534, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7534 .

Traditional Chinese medicine intervention for autism spectrum disorders: A protocol for systematic review and network meta-analysis.

Background:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication, social interaction, and restrictive or repetitive behaviors. Traditional Chinese medicine (TCM) has been used in the clinical management of ASD, especially in mainland China, where studies have shown promising efficacy. However, this remains to be further explored and clarified. Therefore, the purpose of this study was to evaluate the effectiveness and safety of conventional treatment-based TCM interventions for ASD.Method:The study will be conducted from January 2022, and the following electronic databases will be searched: China Biological Medicine Database, Chinese Scientific Journals Database, Wan Fang database, and China National Knowledge Infrastructure, the Cochrane Library, Web of Science, PubMed, and EMBASE Database. Only randomized controlled trials of TCM interventions for ASD will be included. The Autism Diagnostic Observation Scale, Autism Diagnostic Interview-Revised, and Childhood Autism Rating Scale will be the primary outcome indicators. The methodological quality of this Bayesian-based network meta-analysis will be performed using the “Risk of Bias” tool. Stata 14.0 and WinBUGS 1.4.3 will be used to analyze the data. In addition, assessment of heterogeneity, inconsistency, subgroups, sensitivity, and publication bias will be conducted using the Cochrane Collaboration's tools.Results:The results of this study will be submitted to a peer-reviewed journal for publication.Conclusion:This study will help patients recover better, provide clinical evidence for practitioners, and promote the use of TCM in ASD interventions.

Functional connectivity during language processing in 3-month-old infants at familial risk for autism spectrum disorder.

Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3months of age-differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18months. We measured spectral power and phase coherence in the theta (4-6Hz) and alpha (6-12Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n=14) and No-ASD-concern (n=49) outcome groups based on their ASD symptoms at 18months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend toward reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18months. Across outcome groups, alpha coherence at 3months correlated with greater word production at 18months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact, and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5min of ASL, can be quantified as early as 3months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.

Extracting Latent Subdimensions of Social Communication: A Cross-Measure Factor Analysis

Social communication deficits associated with autism spectrum disorder (ASD) are commonly represented as a single behavioral domain. However, increased precision of measurement of social communication is needed to promote more nuanced phenotyping, both within the autism spectrum and across diagnostic boundaries. A large sample (N= 1,470) of 4- to 10-year-old children was aggregated from across 4 data sources, and then randomly split into testing and validation samples. A total of 57 selected social communication items from 3 widely used autism symptom measures (the Autism Diagnostic Observation Scale [ADOS], Autism Diagnostic Interview-Revised [ADI-R], and Social Responsiveness Scale [SRS]) were analyzed in the multi-trait/multi-method factor analysis framework. The selected model was then confirmed with the validation sample. The 4-substantive factor model, with 3 orthogonal method factors, was selected using the testing sample based on fit indices and then confirmed with the validation sample. Two of the factors, "Basic Social Communication Skills" and "Interaction Quality," were similar to those identified in a previous analysis of the ADOS, Module 3. Two additional factors, "Peer Interaction and Modification of Behavior" and "Social Initiation and Affiliation," also emerged. Factor scores showed nominal correlations with age and verbal IQ. Identification of subdimensions could inform the creation of better conceptual models of social communication impairments, including mapping of how the cascading effects of social communication deficits unfold in ASD versus other disorders. Especially if extended to include both older and younger age cohorts and individuals with more varying developmental levels, these efforts could inform phenotype-based exploration for biological and genetic mechanisms by pinpointing specific mechanisms that contribute to various types of social communication deficits.

Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study

IntroductionChildren with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children...

Sensitivity and Specificity of the ADOS-2 Algorithm in a Large German Sample

The aim of the present study was to establish diagnostic validity of the new algorithm of the Autism Diagnostic Observation Scale, the ADOS-2, to differentiate between ASD and other clinically relevant psychiatric and developmental disorders in a large German sample. Validity of ADOS and ADOS-2 diagnostic algorithms was established in 826 individuals (n = 455 autism, n = 216 autism spectrum, n = 155 non-ASD patients) by receiver operating curves. Confidence intervals overlapped largely for ADOS and ADOS-2 algorithms, confirming diagnostic validity of both algorithms. Adding information of the Social Communication Questionnaire and the Social Responsiveness Scale resulted in slightly improved classification rates for autism in Module 4. We thus replicated previous findings of the diagnostic validity of the ADOS-2 algorithms.

A Brief Introduction to the Measurement and Classification of Restricted and Repetitive Behaviors in Autism Spectrum Disorders

Restricted and repetitive behaviors (RRB) is one of the core features of autism spectrum disorder (ASD) which consists of a group of heterogeneous behaviors. Tools of the measurement of RRBs mainly include direct clinical observation of children (such as Autism Diagnostic Observation Scale, ADOS), parental development history interview (Autism Diagnostic Interview-Revised, ADI-R) and parental questionnaire (Repetitive Behavior Scale-Revised. RBS-R, etc.). Using these scales, a number of studies have classified RRBs into repetitive sensory motor (RSM) and insistence on sameness (IS), corresponding to lower level and higher level RRBs respectively. A third factor circumstanced interest (CI) may also exist. Factors influencing the severity of RRBs includes age and IQ. Further researches should focus on integrating phenotypic and pathological studies of RRBs.

Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex: a clinical epidemiological study

Tuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial migration line (RML) count and location, and cognitive functioning in 52 children with TSC and performed regression and mediation analyses. Tuber and RML count were strongly positively related to ASD severity. However, when correcting for cognitive functioning, the majority of associations became insignificant and only total tuber count remained associated to the severity of restricted/repetitive behaviors. Occipital RML count remained associated with overall ASD severity, and social communication/interaction deficit severity specifically. This study shows the important explanatory role of cognitive functioning in the association between cortical dysplasia and ASD severity, and the relevance of separately studying the two ASD subdomains.

Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway.

To investigate the cognitive and behavioural phenotype in rare disorders of the Ras/MAPK pathway, namely Noonan, cardiofaciocutaneous (CFC), and Costello syndromes, particularly prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD). Fifty children were recruited over 10 months through the regional genetics service and advertisements. A range of parent, child, and observational measures were administered including Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Scale. Using the Collaborative Programme for Excellence in Autism criteria, 12 out of 40 children with Noonan syndrome (30%) showed ASD, and 12 out of 40 (30%) with partial ASD features and 16 out of 40 (40%) showed non-ASD. The Noonan syndrome ASD group showed male dominance in a ratio of 5:1. In the CFC group, eight out of nine children met the criteria for ASD, with equal sex distribution. Additionally 19 out of 40 (48%) of the Noonan syndrome group and eight out of nine (88.9%) of the CFC group scored met clinical criteria for ADHD. Only one child was in the Costello syndrome group. This is the first systematic study to suggest a high prevalence of ASD in Noonan and CFC syndromes, and thus offers crucial evidence to support the importance of the Ras/MAPK pathway in the aetiology of ASD. Limitations include the inevitable possibility of a sampling bias in a rare disorder study of this kind.

Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies.

Rating scale measures are associated with Noldus EthoVision-XT video tracking of behaviors of children on the autism spectrum

BackgroundChildren with Autism Spectrum Disorder (ASD) show unusual social behaviors and repetitive behaviors. Some of these behaviors, e.g., time spent in an area or turning rate/direction, can be automatically tracked. Automated tracking has several advantages over subjective ratings including reliability, amount of information provided, and consistency across laboratories, and is potentially of importance for diagnosis, animal models and objective assessment of treatment efficacy. However, its validity for ASD has not been examined. In this exploratory study, we examined associations between rating scale data with automated tracking of children’s movements using the Noldus EthoVision XT system; i.e., tracking not involving a human observer. Based on our observations and previous research, we predicted that time spent in the periphery of the room would be associated with autism severity and that rate and direction of turning would be associated with stereotypies.MethodsChildren with and without ASD were observed in a free-play situation for 3 min before and 3 min after Autism Diagnostic Observation Scale – Generic (ADOS-G) testing. The Noldus system provided measures of the rate and direction of turning, latency to approach and time spend near the periphery or the parent.ResultsRatings of the severity of maladaptive social behaviors, stereotypies, autism severity, and arousal problems were positively correlated with increases in percent time spent in the periphery in the total sample and in the ASD subset. Adaptive social communication skills decreased with increases in the percentage of time spent in the periphery and increases in the latency to approach the parent in the ASD group. The rate and direction of turning was linked with stereotypies only in the group without ASD (the faster the rate of a turn to the left, the worse the rating). In the ASD group, there was a shift from a neutral turning bias prior to the ADOS assessment to a strong left turn bias after the ADOS assessment. In the entire sample, this left turn bias was associated with measures of autism severity.ConclusionResults suggest that automated tracking yields valid and unbiased information for assessing children with autism. Turning bias is an interesting and unexplored measure related to autism.

The Interstitial Duplication 15q11.2‐q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature

Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum.

Commentary: Advancing measurement of ASD severity and social competence: a reply to Constantino and Frazier (2013)

Commentary: Advancing measurement of ASD severity and social competence: a reply to Constantino and Frazier (2013)

The Prevalence of Gastrointestinal Problems in Children Across the United States With Autism Spectrum Disorders From Families With Multiple Affected Members

: To perform a large registry-based study to determine the relative prevalence of gastrointestinal (GI) problems in children with an autism spectrum disorder (ASD) from families with multiple affected members compared with their unaffected sibling(s). : In-home structured retrospective medical history interviews by parent recall were conducted by a pediatric neurologist. Our analysis sample included information about GI health of 589 subjects with idiopathic, familial ASD and 163 of their unaffected sibling controls registered with Autism Genetic Resource Exchange. Individuals with ASD were subgrouped into 3 autism severity groups (Full Autism, Almost Autism, and Spectrum) based on their Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Scale scores. : Parents reported significantly more GI problems in children with ASD (249/589; 42%) compared with their unaffected siblings (20/163; 12%) (p < .001). The 2 most common Gl problems in children with ASD were constipation (116/589; 20%) and chronic diarrhea (111/589; 19%). Conditional logistic regression analysis showed that having Full Autism (adjusted odds ratio [AOR] = 14.28, 95% confidence interval [CI]: 6.22-32.77) or Almost Autism (AOR = 5.16, 95% CI 2.02-13.21) was most highly associated with experiencing GI problems. Increased autism symptom severity was associated with higher odds of GI problems (AOR for trend = 2.63, 95% CI: 1.56-4.45). : Parents report significantly more GI problems in children with familial ASD, especially those with Full Autism, than in their unaffected children. Increased autism symptom severity is associated with increased odds of having GI problems.

Developmental and Behavioral Questionnaire for Autism Spectrum Disorders

The validity of the Parental Concerns Questionnaire, a brief screening checklist assessing the presence and severity of 13 developmental and behavioral concerns expressed by parents of children with autism spectrum disorders, was determined in 53 children ages 4 to 10 years with a clinical diagnosis of autism spectrum disorder and 48 age-matched typically developing controls. Parents completed the Parental Concerns Questionnaire, the Child Behavior Checklist, the Child Sleep Habits Questionnaire, and either the Repetitive Behavior Scale or the Compulsive Behavior Checklist. A clinical examiner administered the Peabody Picture Vocabulary Test and the Autism Diagnostic Observation Scale. The Parental Concerns Questionnaire demonstrated high internal consistency in the autism spectrum disorder subgroup. Reliability and stability over time were demonstrated. Analyses showed variability in item responses for each child indicating that parents were not globally answering all items as concerns. Comparison of Parental Concerns Questionnaire item scores to scores for similar multiquestion domains on standardized parent-rated and clinician-administered assessment tools demonstrated external validity with other parent-rated and clinician-rated instruments. The Parental Concerns Questionnaire is a reliable screening instrument to assess parentally reported developmental and behavioral symptoms in children with autism spectrum disorders.

Continuity and change from early childhood to adolescence in autism

This longitudinal study of 48 children diagnosed with autism at 2-5 years of age was designed to test the hypothesis that diagnosis would remain stable for most of the sample but that there would be improvements in symptom severity, adaptive behavior, and emotional responsiveness in adolescence. A sample of children with autism assessed in both early and middle childhood were observed in late adolescence with the Autism Diagnostic Observation Scale (ADOS) and their parents were administered the Autism Diagnostic Interview-Revised (ADI-R) and the Vineland Adaptive Behavior Scale. All but 2 adolescents (46 of 48) met lifetime criteria for autism according to the ADI-R, and all but 4 adolescents (40 of 44) met criteria for autism spectrum disorder on the ADOS. In contrast to the continuity in diagnosis, parents described improvements in social interactions, repetitive/stereotyped behaviors, adaptive behaviors, and emotional responsiveness to others' distress in adolescence compared to middle childhood. High-functioning adolescents with autism showed more improvement in these domains than low-functioning adolescents with autism. The extent to which the adolescents were observed to be socially engaged with their peers in school in middle childhood predicted adaptive behavior skills even when intelligence level was statistically constrained. The developmental trajectory of children with autism appears to show both continuity and change. In this sample, most individuals continued to be diagnosed in the autism spectrum but parents reported improvements in adolescence. The results suggest that social involvement with peers improves adaptive behavior skills, and this argues for focusing intervention programs in this area. In addition, it is clear that high-functioning adolescents improve more than low-functioning individuals not only in cognitive abilities but also in social interaction skills. Thus, any early intervention that impacts the cognitive abilities of young children with autism is likely to have a parallel influence on their social skills as they mature into late adolescence and early adulthood.

In children with autism, is intravenous secretin more effective than placebo in improving social skills, communication, behaviour or global functioning?

In children with autism, is intravenous secretin more effective than placebo in improving social skills, communication, behaviour or global functioning?

Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients.

A genetic etiology in autism is now strongly supported by family and twin studies. A 3:1 ratio of affected males to females suggests the involvement of at least one X-linked locus in the disease. Several reports have indicated an association of the fragile X chromosomal anomaly at Xq27.3 (FRAXA) with autism, whereas others have not supported this finding. We have so far collected blood from 105 simplex and 18 multiplex families and have assessed 141 patients by using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Scale, and psychometric tests. All four ADI-R algorithm criteria were met by 131 patients (93%), whereas 10 patients (7%) showed a broader phenotype of autism. Southern blot analysis was performed with three different enzymes, and filters were hybridized to an FMR-1-specific probe to detect amplification of the CCG repeat at FRAXA, to the complete FMR-1 cDNA probe, and to additional probes from the neighborhood of the gene. No significant changes were found in 139 patients (99%) from 122 families, other than the normal variations in the population. In the case of one multiplex family with three children showing no dysmorphic features of the fragile X syndrome (one male meeting 3 out of 4 ADI-algorithm criteria, one normal male with slight learning disability but negative ADI-R testing, and one fully autistic female), the FRAXA full-mutation-specific CCG-repeat expansion in the genotype was not correlated with the autism phenotype. Further analysis revealed a mosaic pattern of methylation at the FMR-1 gene locus in the two sons of the family, indicating at least a partly functional gene. Therefore, we conclude that the association of autism with fragile X at Xq27.3 is non-existent and exclude this location as a candidate gene region for autism.

Genetics of autism: characteristics of affected and unaffected children from 37 multiplex families.

Evidence from twin and family studies strongly suggests that genetic factors play a prominent role in the etiology of some cases of infantile autism. Genetic factors would be expected to be especially strong in families with multiple autistic members (multiplex families). This report describes the identification and evaluation of 44 families with two or more autistic children collected as part of a genetic linkage study in autism. Families were referred with a presumptive classification of multiplex autism. Children referred as autistic, as well as their presumptively normal siblings, were assessed using the Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Scale (ADOS). Thirty-seven of the 44 families (87%) had at least two children who met diagnostic criteria for autism on the ADI. Of the total group of 117 children evaluated in those families, 83 (71%) met all ADI criteria and could be unambiguously classified as autistic (affected), 26 (22%) met none of the ADI criteria and were classified as not autistic (unaffected), and 8 (7%) were classified as uncertain because they met one or more but not all of the ADI cutpoints. Autistic siblings were not significantly concordant for most autism characteristics, for IQ, or for verbal ability. Significant concordances were found, however, for behaviors related to rituals and repetitive play, and for social impairments in the expression and understanding of facial expressions of emotion.(ABSTRACT TRUNCATED AT 250 WORDS)