ADOS-2 Module 4: Psychometric Properties and Diagnostic Performance at an Autism-specialized Clinic.

PURPOSE: Psychometric properties and diagnostic performance of the ADOS-2 module 4 were evaluated with participants from an autism-specialized clinic. METHODS: The sample had 331 participants with 226 males and 70 females receiving an ASD diagnosis. The evaluation consisted of the following: (1) A replication of the Exploratory Factor Analysis (EFA) reported by Hus, V., & Lord, C. (2014). The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores. Journal of Autism and Developmental Disorders, 44(8), 1996-2012. https://doi.org/10.1007/s10803014-2080-3 .). (2) Identification of ADOS-2 items best predicting clinical diagnosis using Recursive Feature Elimination (RFE) and comparison of these items to previous findings. (3) Receiver Operating Characteristic (ROC) curve analyses of the effects of age and IQ on diagnostic performance. (4) Comparisons of ADOS-2 revised algorithm scores between females and males and their association with ADI-R scores. RESULTS: The EFA item-to-factor allocation of the ADOS-2 revised algorithm was largely reproduced. When comparing the present RFE to previous RFE findings, the item Quality of Social Responses stood out. ROC curve analysis showed outstanding diagnostic performance for adults with IQ above 70 but for females, ADOS-2 revised algorithm scores were lowered, and, contrary to males, did not correlate with ADI-R scores. CONCLUSION: Reproducing the item-to-factor allocation and finding outstanding agreement with the diagnostic decision for adults with IQ > 70 showcase the strength of the ADOS-2 revised algorithm. Furthermore, by incorporating, into future revisions, the finding of inter-clinic importance of the item Quality of Social Responses, performance might be further enhanced. Lastly, though, that female scores were lowered and did not correlate with ADI-R indicate a weakness in the ADOS-2 when applied to the adult female population.

Well-Being and Self-Disorders in Schizotypal Disorder and Asperger Syndrome/Autism Spectrum Disorder.

We explored subjective well-being in two groups of young adult participants diagnosed with either schizotypal disorder (Sd) (n = 29) or Asperger syndrome/autism spectrum disorder (As/ASD) (n = 22). Well-being was impaired in both groups and was lower in the Sd group than in the As/ASD group. Furthermore, there was a negative correlation between well-being and the presence of self-disorders. The negative effect of self-disorders on well-being was still significant when adjusted for diagnosis, age and gender, and level of function. The present findings point toward clinically important disorder-specific differences in the nature of impaired well-being between the Sd group and the As/ASD group, as there seems to be a self-disorder-driven additional contribution to impaired subjective well-being within the schizophrenia spectrum. These findings further nuance the understanding of fundamental and clinically important qualitative differences between the schizophrenia spectrum and the autism spectrum.

Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder: A Clinical Study.

OBJECTIVE: There are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum. METHODS: All participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: A total of 51 participants (As/ASD, n = 22; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups. CONCLUSION: Our results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.

Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden.

Introduction: The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods: A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion: The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion: All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible.

Arguments for a Phenomenologically Informed Clinical Approach to Autism Spectrum Disorder.

OBJECTIVE: The aim of this paper is to provide arguments for a phenomenologically informed clinical approach to autism spectrum disorder (ASD), including a plea for clinical attention to the self in ASD. METHODS: Central concepts of continental phenomenology, phenomenological psychopathology, and the phenomenological interview are presented, with an emphasis on the potential unifying qualities of an approach which includes the exploration of subjective and intersubjective experience. These phenomenological concepts and methods are contrasted with the current conceptualization of ASD, where the first-person perspective is not in focus. RESULTS: Contemporary phenomenological papers on ASD address key concepts like intersubjectivity, intercorporeality, and intentionality. However, insights from this theoretical field have not been followed up in clinical research and practice. Consequently, there is (to our knowledge) still a lack of phenomenologically informed clinical explorations of experience of self, others, and the world in ASD. CONCLUSION: A phenomenologically informed focus on the form and structure of subjective experience, including a focus on self-experience in ASD, can lead to new and important insights in relation to clinical differentiation between ASD and schizophrenia spectrum disorder.

Impairment of Social Function in Young Females With Recent-Onset Anorexia Nervosa and Recovered Individuals.

PURPOSE: A subgroup of individuals with anorexia nervosa (AN) displays social difficulties; however, it is not clear if individuals with comorbid autism spectrum disorders account for these difficulties. METHODS: We compared social function using the Autism Diagnostic Observation Schedule in 43 young females with first-episode AN who did not have comorbid autism spectrum disorder, 28 individuals recovered from adolescent-onset AN, and 41 healthy comparison individuals (age range 14-22 years). We measured adaptive behavior with the Vineland-II parent questionnaire, and aspects of social cognition with psychological tests, such as the Reading-the-Mind-in-the-Eyes test, Profile of Nonverbal Sensitivity short version, The Awareness of Social Inference Test, Animated Triangles, and the CANTAB Affective Go/No-go task. RESULTS: Participants with first-episode AN and those recovered from AN displayed difficulties in social function, which were not associated with body mass index or other state factors of the disorder in those with first-episode AN. Mood problems and anxiety were not associated with these difficulties. Parents rated participants with first-episode AN lower than recovered and control participants on the Socialization Domain of Vineland-II. Finally, only participants recovered from AN demonstrated deficits in specific domains of social cognition: perceiving nonverbal bodily gesture and vocal prosody. CONCLUSIONS: Young females with first-episode AN and those recovered from AN displayed impairments in social function, which may represent more stable traits of the disorder. Only participants recovered from AN demonstrated deficits in social cognition.

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP.

Data mining the ScanBrit study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders: behavioural and psychometric measures of dietary response.

We previously reported results based on the examination of a gluten- and casein-free diet as an intervention for children diagnosed with an autism spectrum disorder as part of the ScanBrit collaboration. Analysis based on grouped results indicated several significant differences between dietary and non-dietary participants across various core and peripheral areas of functioning. Results also indicated some disparity in individual responses to dietary modification potentially indicative of responder and non-responder differences. Further examination of the behavioural and psychometric data garnered from participants was undertaken, with a view to determining potential factors pertinent to response to dietary intervention. Participants with clinically significant scores indicative of inattention and hyperactivity behaviours and who had a significant positive changes to said scores were defined as responders to the dietary intervention. Analyses indicated several factors to be potentially pertinent to a positive response to dietary intervention in terms of symptom presentation. Chronological age was found to be the strongest predictor of response, where those participants aged between 7 and 9 years seemed to derive most benefit from dietary intervention. Further analysis based on the criteria for original study inclusion on the presence of the urine compound, trans-indolyl-3-acryloylglycine may also merit further investigation. These preliminary observations on potential best responder characteristics to a gluten- and casein-free diet for children with autism require independent replication.

Toward high-throughput drug screening on a chip-based parallel affinity separation platform.

High-throughput screening of compound libraries, including the study of fragments, has become one of the cornerstones in modern drug discovery research. During this process hits are defined that may be developed into valuable leads and eventually into possible drug candidates. In this paper, we have demonstrated that parallel zonal weak affinity chromatography in microcolumns on a chip offers a possible screening format for weakly binding ligands toward a protein target. We used albumin as a model system because this transport protein is well established as a binder (both weak and strong) for drug substances. Bovine serum albumin was immobilized on microparticulate diolsilica particles and then packed into a 24-channel cartridge, which served as the separation platform. Analysis of the obtained chromatograms yielded information about affinity even in the millimolar range. Employing this approach, thousands of substances can be screened in just a day. We feel confident that zonal affinity chromatography will provide a useful technology in the future for performing high-throughput screening.

The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders.

There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomisation. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) to determine inattention and hyperactivity. Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment. Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention. The study was registered with ClincialTrials.gov, number NCT00614198.

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q.

Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.