Identifying Autistic-Like Symptoms in Children with ADHD: A Comparative Study Using ADOS-2.

Purpose: Recent literature has focused attention on the presence of autistic-like symptoms in children with Attention Deficit/Hyperactivity Disorder (ADHD), who often exhibit social difficulties, posing challenges for a distinct clinical diagnosis. The current study aimed to identify the specific pattern of autistic symptoms in subjects with ADHD or Autistic Spectrum Disorder (ASD), examining similarities or differences at both the domain and individual item levels. Patients and Methods: In this study, we enrolled 43 school-age children divided into the following: the ADHD group (n=25) consisted of children initially referred for ASD symptoms but subsequently clinically diagnosed with ADHD, and the ASD group consisted of 18 children with ASD. We used the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), to examine relative differences in the presence of symptoms such as deficits in communication and social interaction, and restricted and repetitive behaviors in these two groups. Comparison between groups was conducted to explore differences in IQ, age, ADOS-2 domains, and externalizing and internalizing problems among the groups. Results: We found significant differences between the groups when comparing summary scores of ADOS-2 domains (Social Affect, Restricted and Repetitive Behavior, and Total Score). Interestingly, at the individual item level, the ADHD group exhibited a similar level of atypical behaviors compared to the ASD group in two items related to the social-communication area: "Pointing" and "Gestures". Additionally, the frequencies of "Stereotyped/idiosyncratic words or phrases", "Mannerisms", and "Repetitive interests and behaviors" also showed similarities between groups. Conclusion: These findings indicate the importance of exploring and developing potential transdiagnostic domains that could be targeted for treatments specifically designed for children with ADHD.

A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are neurodevelopmental conditions which frequently co-occur. The Autism Diagnostic Observation Schedule (ADOS) is commonly used to aid with diagnostic assessment of ASD but was not originally designed for use in those with comorbid ADHD. Visual attention to social stimuli has been often studied in ASD using eye-tracking, to obtain quantitative indices of how attention is deployed to different parts of a social image/scene. As the ADOS includes tasks that rely on attending to and processing images of social scenes, these measures of visual attention could provide useful additional objective measurement alongside ADOS scores to enhance the characterisation of autistic symptoms in those with ADHD. Methods: Children with ASD, comorbid ASD and ADHD, ADHD and Neurotypical (NT) controls were recruited (n=84). Visual attention was measured using eye-tracking during free viewing of social scenes selected from the ADOS. The full ADOS was then administered. Stimulant medication was temporarily withdrawn during this assessment. Research diagnoses were based on the Development and Wellbeing Assessment (DAWBA), ADOS, Social Communication Questionnaire (SCQ, a measure of ASD severity) and Conners' Rating Scales (CRS-3, a measure of ADHD severity) following clinical consensus. Results: Using factorial ANOVAs to model ADHD, Autism and their interaction, we found that fixation duration to faces was reduced in those with ASD (ASD and ASD+ADHD) compared to those without ASD (ADHD and NT). Reduced visual attention to faces in the whole sample was associated with Autism symptom severity (SCQ subscale scores) but not ADHD symptom severity (CRS-3 scores). Discussion: Our findings provide preliminary evidence in support of implementing visual attention measurement during assessment of ASD in the context of comorbidity with ADHD. For example, if a child with ADHD was found to reduce attention to faces in ADOS pictures this may suggest additive difficulties on the autism spectrum. Replication across a larger sample would be informative. This work has future potential in the clinic to help with complex cases, including those with co-occurring ADHD and ASD.

Objective Measurement of Social Gaze and Smile Behaviors in Children with Suspected Autism Spectrum Disorder During Administration of the Autism Diagnostic Observation Schedule, 2nd Edition.

Best practice for the assessment of autism spectrum disorder (ASD) symptom severity relies on clinician ratings of the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2), but the association of these ratings with objective measures of children's social gaze and smiling is unknown. Sixty-six preschool-age children (49 boys, M = 39.97 months, SD = 10.58) with suspected ASD (61 confirmed ASD) were administered the ADOS-2 and provided social affect calibrated severity scores (SA CSS). Children's social gaze and smiling during the ADOS-2, captured with a camera contained in eyeglasses worn by the examiner and parent, were obtained via a computer vision processing pipeline. Children who gazed more at their parents (p = .04) and whose gaze at their parents involved more smiling (p = .02) received lower social affect severity scores, indicating fewer social affect symptoms, adjusted R2 = .15, p = .003.

Examine sex differences in autism spectrum disorder in school-aged children and adolescents with fluent language.

There are noteworthy sex disparities in the prevalence of autism spectrum disorders (ASD), while findings regarding the sex differences in core symptoms are inconsistent. There are few relevant studies on sex differences in mainland China. This study was dedicated to a deeper understanding of the impact of sex differences on the clinical presentation of ASD with fluent language. We retrospectively studied 301 children with ASD (58 females) and utilized raw scores from the ADI-R and ADOS and the intelligence quotient (IQ) to measure symptomatology. Based on the Full-Scale IQ (FS-IQ), a binary split of average, above-average IQ (high-IQ), and below-average IQ (low IQ) occurs at 85. Across the entire sample, males and females are comparable in the FS-IQ, while males scored higher in the Perceptual Reasoning Index (PRI) (F = 7.812, p = 0.006). ADI-R did not find any statistically significant sex differences in the diagnostic cutoff score satisfaction or the raw domain scores. While a significant effect of sex on ADOS social affect domain scores was found in the total sample [λ = 0.970, partial η2 = 0.030, F (3,295) = 3.019, p = 0.030]. Tests of between-subjects effects revealed that males scored higher than females mainly in the ADOS reciprocal social interaction subcategory (partial η2 = 0.022, F = 6.563, p = 0.011). Stratified analysis revealed that the effect of sex on ADOS reciprocal social interaction subcategory scores only significant in the low-IQ children with ASD (partial η2 = 0.092, F = 10.088, p = 0.002). In general, overall cognitive functioning is similar across males and females with ASD, while males have a higher perceptual reasoning ability. Females with ASD are more likely to have comorbid intellectual impairment than males, and they could require additional intervention support. Autistic children with low IQs are more likely to exhibit sex differences in their core symptoms than children with high IQs. Intelligence plays a key role in sex-based differences in the core symptoms of ASD.

Comparison of an online adaptation of the Autism Diagnostic Observation Schedule-2 with its in-person version in an adult autism diagnostic service.

BACKGROUND: Restrictions on in-person assessments during the COVID-19 pandemic were a challenge for an adult autism diagnostic service receiving over 600 referrals annually. The service sought to adapt the Autism Diagnostic Observation Schedule (ADOS-2) for online administration. AIMS: To investigate whether an online adaptation of the ADOS-2 performed comparably to the in-person ADOS-2. To obtain qualitative feedback from patients and clinicians regarding experiences of the online alternative. METHOD: Online ADOS-2 assessments were completed for 163 referred individuals. A matched-comparison group comprised 198 individuals seen for an in-person ADOS-2 assessment prior to COVID-19 restrictions. A two-way analysis of variance (ANOVA) was run to explore any effect of assessment type (online or in-person ADOS-2) and gender on total ADOS score. Qualitative feedback was collected from 46 patients and 8 clinicians involved in diagnostic decision-making after the online ADOS-2 assessment. RESULTS: A two-way ANOVA found no significant effect of assessment type or gender and no assessment type × gender interaction effect on total ADOS score. Qualitative feedback suggested that only 27% of patients would have preferred an in-person assessment. Nearly all clinicians reported gains from offering an online alternative. CONCLUSIONS: This is the first study to examine an online adaptation of ADOS-2 within an adult autism diagnostic service. It performed comparably to the in-person ADOS-2, making it a viable alternative when in-person assessments are not possible. As this clinic group has high rates of comorbid mental health difficulties, we encourage further work to determine whether online assessment approaches generalise to other services to increase options for patients and efficiencies for service delivery.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Comparing autism phenotypes in children born extremely preterm and born at term.

Children born preterm are at increased risk for autism spectrum disorder (ASD). There is limited knowledge about whether ASD phenotypes in children born preterm differ from children born at term. The objective of this study was to compare ASD core symptoms and associated characteristics among extremely preterm (EP) and term-born children with ASD. EP participants (n = 59) from the Extremely Low Gestational Age Newborn Study who met diagnostic criteria for ASD at approximately 10 years of age were matched with term-born participants from the Simons Simplex Collection on age, sex, spoken language level, and nonverbal IQ. Core ASD symptomatology was evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Developmental milestones, anthropometrics, seizure disorder, and psychiatric symptoms were also investigated. The EP group had lower parent-reported symptom scores on ADI-R verbal communication, specifically stereotyped language, and restricted, repetitive behaviors. There were no between-group differences on ADI-R nonverbal communication and ADI-R reciprocal social interaction or with direct observation on the ADOS-2. The EP group was more likely to have delayed speech milestones and lower physical growth parameters. Results from female-only analyses were similar to those from whole-group analyses. In sum, behavioral presentation was similar between EP and IQ- and sex-matched term-born children assessed at age 10 years, with the exception of less severe retrospectively reported stereotyped behaviors, lower physical growth parameters, and increased delays in language milestones among EP-born children with ASD.

Autistic traits of children born very preterm assessed using Autism Diagnostic Observation Schedule, Second Edition.

Preterm birth has been linked with increased incidence of autism spectrum disorder (ASD). Despite the remarkable difference in the clinical backgrounds between ASD children born preterm and term, cross-sectional studies have found no striking difference in their autistic traits. To highlight autistic traits related with preterm birth, children born very preterm (prospective birth cohort, n = 50) and term (case cohort, n = 16), who were diagnosed as "Autism" by the Autism Diagnostic Observation Schedule (ADOS), 2nd edition, were compared using the calibrated severity scores of ADOS-2 and T-scores of the Social Responsiveness Scale, 2nd edition. No significant difference was found in the calibrated severity scores between ASD children born preterm and term. There was a trend that T-scores were smaller for the preterm cohort, which did not reach a statistical significance. Even when detailed cross-sectional information was obtained using ADOS-2, no difference in autistic traits was observed between children born very preterm and term. Our findings were consistent with a previous study, which assessed the entire prospective cohort of children born very preterm and found no difference in original ADOS scores. Further studies are warranted to delineate how preterm birth affects the autistic traits and their parental perception in a large prospective cohort.

Social and Nonsocial Autism Symptom Domains in Children and Adolescents with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder: Insights into Their Symptomatological Interplay.

INTRODUCTION: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share overlapping symptomatology, particularly with regard to social impairments (including peer relationship difficulties), and they frequently co-occur. However, the nature of their co-occurrence remains unclear. Therefore, the current study aimed to examine the nature of the transdiagnostic link between ASD and ADHD from a symptomatological point of view measured with the Autism Diagnostic Observation Schedule (ADOS Module 3) and the Autism Diagnostic Interview-Revised (ADI-R). METHODS: We analyzed the social and nonsocial ASD symptom domain scores from both diagnostic instruments in 4 clinically referred groups (i.e., ASD, ADHD, ASD + ADHD, and no psychiatric diagnosis) without other co-occurring mental disorders using a two-by-two full-factorial MANOVA design with the factors ASD (yes/no) and ADHD (yes/no). RESULTS: We found no ASD by ADHD interaction effects across all symptom domain scores of ADOS and ADI-R, except for ADOS imagination/creativity. There were only main effects of the factor ASD but no main effects of ADHD. Follow-up contrasts showed that exclusively, ASD had an impact on the measured symptomatology in case of co-occurring ASD + ADHD. CONCLUSION: Overall, the results support an additive model of the symptomatology across areas of communication, social interaction, and stereotyped behaviors and restricted interests in case of the co-occurrence of ASD and ADHD when assessed with ADOS/ADI-R. Thus, one can assume that the phenotypic overlap of ASD + ADHD may be less complicated than suspected - at least with regard to ASD symptomatology - and that in the presence of ADHD, ASD symptomatology is generally well measurable with best-practice diagnostic instruments.

Delineating the autistic phenotype in children with neurofibromatosis type 1.

BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.

Diagnostic rate of autism spectrum disorder in a high-survival cohort of children born very preterm: A cross-sectional study.

To investigate the diagnostic rate of autism spectrum disorder (ASD) in a high-survival cohort of very preterm children, 77 infants born very preterm (<32 weeks of gestation) were assessed at age 4-6 years old using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Sixteen children (20.8%) were classified as both DSM-5-positive ASD and ADOS-2-identified "autism," which were defined as confirmed ASD in this study. Our result suggests that the prevalence of ASD in very preterm children might be much higher than reported in previous studies when all children were individually evaluated. Further studies in a large sample are required to clarify the true risk of ASD in preterm birth.

Differentiation of autism spectrum disorder and mood or anxiety disorder.

LAY ABSTRACT: Symptoms of mood and anxiety disorders overlap with symptoms of autism spectrum disorder, making the diagnostic process challenging. This study found that a combination of communicational deficits and unusual and/or inappropriate social overtures facilitates differentiation between autism spectrum disorder and mood and anxiety disorders. Furthermore, the results confirm the essential need of a behavioral observation with the Autism Diagnostic Observation Schedule in combination with a full Autism Diagnostic Interview-Revised to support diagnostic decisions.

Adapting and validating the Autism Diagnostic Observation Schedule Version 2 for use with deaf children and young people.

We report a Delphi Consensus modification and first validation study of the Autism Diagnostic Observation Schedule - 2 with deaf children and young people (ADOS-2 Deaf adaptation). Validation included 122 deaf participants (aged 2-18 years), 63 with an Autism Spectrum Disorder (ASD). This was compared to a National Institute for Health and Clinical Excellence (NICE) guideline standard clinical assessment by blinded independent specialist clinicians. Results showed overall sensitivity 73% (95%CI 60%, 83%); specificity 71% (95%CI 58%, 82%), and for the more common modules 1-3 (combined as in previous studies) sensitivity 79% (95% CI 65-89%); specificity 79% (95% CI 66-89%) suggesting this instrument will be a helpful addition for use with deaf children and young people.

Eating Behaviors of Children with Autism-Pilot Study, Part II.

Autism spectrum disorder is characterized by social communication deficit and non-normative behavior. The people with autism often experience troubles with feeding. The purpose of this study was to conduct evaluation of the feeding and eating behaviors among children with autism. PATIENTS AND METHODS: The study group included 41 high-functioning autistic children. The control group consisted of 34 children without the ASD. The questionnaire was used to assess the nutritional status. RESULTS: The children with ASD fuss during mealtimes more frequently, they require entertaining and diverting their attention, they are fed by parents, and they consume their meals away from the table. The significant difference found in the use of utensils and food selectivity works to the disadvantage of the Study Group. CONCLUSIONS: The food selectivity occurs significantly more frequently among children with ASD. The feeding and eating problems should be considered on a wider scale. The cooperation of the multidisciplinary and the parents teams should be proposed in the ASD patients care.

Joint attention and intelligence in children with autism spectrum disorder without severe intellectual disability.

In children with autism spectrum disorder (ASD), joint attention is regarded as a predictor of language function, social skills, communication, adaptive function, and intelligence. However, existing information about the association between joint attention and intelligence is limited. Most such studies have examined children with low intelligence. For this study, we investigated whether joint attention is related to intelligence in young children with autism spectrum disorder (ASD) without severe intellectual disability. We analyzed 113 children with ASD aged 40-98 months. Their Kaufman Assessment Battery (K-ABC) Mental Processing Index (MPI) scores are 60 and more (mean 93.4). We evaluated their intelligence using K-ABC and evaluated their joint attention using ADOS-2. After we performed simple regression analyses using K-ABC MPI and its nine subscales as dependent variables, using joint attention as the independent variable, we identified joint attention as a positive predictor of the MPI and its two subscales. From this result, we conclude that joint attention is related to intelligence in young children with ASD without severe intellectual disability. This result suggests a beneficial effect of early intervention targeting joint attention for children with ASD. LAY SUMMARY: Joint attention is the ability to coordinate visual attention with another person and then shift one's gaze toward an object or event. Impairment of joint attention is regarded as an early marker of autism spectrum disorder (ASD). This study revealed impairment of joint attention as associated with lower intelligence in ASD children. These results are expected to constitute a rationale for future studies, particularly addressing beneficial effects of early intervention targeting joint attention for children with ASD.

Autism symptoms in anorexia nervosa: a comparative study with females with autism spectrum disorder.

BACKGROUND: Recent research suggests a link between autism spectrum disorder (ASD) and anorexia nervosa (AN). Individuals with AN show high scores on measures of ASD symptoms, relative to individuals without AN, however, there are currently no studies directly comparing women with AN to women with ASD. The aim of the current study was to examine profiles of ASD symptoms in young women in the acute and recovered stages of AN, women with ASD, and typically developing controls (TD), on both self-report and clinical interview measures. METHODS: Four groups of participants aged 12-30 years were included (n = 218): AN, recovered AN (REC), ASD, and TD. Group differences on the Social Responsiveness Scale, 2nd edition (SRS-2), 10-item Autism Quotient (AQ-10), and the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) were examined. To explore similarities and differences in specific symptom profiles associated with AN and ASD, individual item endorsement on the ADOS-2 was also examined in AN, REC, and ASD. RESULTS: Across measures, women with ASD showed the highest scores, and TDs the lowest. Generally, individuals with AN and REC showed intermediate levels of ASD symptoms, scoring between the other two groups. However, AN and ASD did not differ on restricted interests and repetitive behaviour subscales. The ADOS-2 item 'quality of social response' adequately discriminated between ASD and non-ASD participants. LIMITATIONS: A full diagnostic assessment for ASD was not provided for participants with AN/REC, nor were eating disorders assessed in the ASD group. Therefore, some diagnostic overlap between groups is possible. The cross-sectional design is another limitation. CONCLUSIONS: The results suggest similarities in scores on both self-report and clinical interview measures in AN and ASD. However, individual ADOS-2 item analyses also revealed subtle differences, particularly in reciprocal social interaction. ASD symptoms may be a combination of both state and trait features in AN.

Performance of machine learning classification models of autism using resting-state fMRI is contingent on sample heterogeneity.

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions. In fMRI studies, including most machine learning studies seeking to distinguish ASD from typical developing (TD) samples, cohorts differing in gender and symptom severity composition are often treated statistically as one "ASD group". Using resting-state functional connectivity (FC) data, we implemented random forest to build diagnostic classifiers in 4 ASD samples including a total of 656 participants (NASD = 306, NTD = 350, ages 6-18). Groups were manipulated to titrate heterogeneity of gender and symptom severity and partially overlapped. Each sample differed on inclusionary criteria: (1) all genders, unrestricted severity range; (2) only male participants, unrestricted severity; (3) all genders, higher severity only; (4) only male participants, higher severity. Each set consisted of 200 participants per group (ASD, TD; matched on age and head motion), 160 for training and 40 for validation. FMRI time series from 237 regions of interest (ROIs) were Pearson correlated in a 237×237 FC matrix and classifiers were built using random forest in training samples. Classification accuracies in validation samples were 62.5%, 65%, 70% and 73.75%, respectively for samples 1-4. Connectivity within cingulo-opercular task control (COTC) network, and between COTC ROIs and default mode and dorsal attention network contributed overall most informative features, but features differed across sets. Findings suggest that diagnostic classifiers vary depending on ASD sample composition. Specifically, greater homogeneity of samples regarding gender and symptom severity enhances classifier performance. However, given the true heterogeneity of ASDs, performance metrics alone may not adequately reflect classifier utility.

Neural Biomarkers Distinguish Severe From Mild Autism Spectrum Disorder Among High-Functioning Individuals.

Several previous studies have reported atypicality in resting-state functional connectivity (FC) in autism spectrum disorder (ASD), yet the relatively small effect sizes prevent us from using these characteristics for diagnostic purposes. Here, canonical correlation analysis (CCA) and hierarchical clustering were used to partition the high-functioning ASD group (i.e., the ASD discovery group) into subgroups. A support vector machine (SVM) model was trained through the 10-fold strategy to predict Autism Diagnostic Observation Schedule (ADOS) scores within the ASD discovery group (r = 0.30, P < 0.001, n = 260), which was further validated in an independent sample (i.e., the ASD validation group) (r = 0.35, P = 0.031, n = 29). The neuroimage-based partition derived two subgroups representing severe versus mild autistic patients. We identified FCs that show graded changes in strength from ASD-severe, through ASD-mild, to controls, while the same pattern cannot be observed in partitions based on ADOS score. We also identified FCs that are specific for ASD-mild, similar to a partition based on ADOS score. The current study provided multiple pieces of evidence with replication to show that resting-state functional magnetic resonance imaging (rsfMRI) FCs could serve as neural biomarkers in partitioning high-functioning autistic individuals based on their symptom severity and showing advantages over traditional partition based on ADOS score. Our results also indicate a compensatory role for a frontocortical network in patients with mild ASD, indicating potential targets for future clinical treatments.

Social Attention Deficits in Children With Autism Spectrum Disorder: Task Dependence of Objects vs. Faces Observation Bias.

Social attention deficits represent a central impairment of patients suffering from autism spectrum disorder (ASD), but the nature of such deficits remains controversial. We compared visual attention regarding social (faces) vs. non-social stimuli (objects), in an ecological diagnostic context, in 46 children and adolescents divided in two groups: ASD (N = 23) and typical neurodevelopment (TD) (N = 23), matched for chronological age and intellectual performance. Eye-tracking measures of visual scanning, while exploring and describing scenes from three different tasks from the Autism Diagnostic Observation Schedule (ADOS), were analyzed: "Description of a Picture," "Cartoons," and "Telling a Story from a Book." Our analyses revealed a three-way interaction between Group, Task, and Social vs. Object Stimuli. We found a striking main effect of group and a task dependence of attentional allocation: while the TD attended first and longer to faces, ASD participants became similar to TD when they were asked to look at pictures while telling a story. Our results suggest that social attention allocation is task dependent, raising the question whether spontaneous attention deficits can be rescued by guiding goal-directed actions.

ADOS-Eye-Tracking: The Archimedean Point of View and Its Absence in Autism Spectrum Conditions.

Face perception and emotion categorization are widely investigated under laboratory conditions that are devoid of real social interaction. Using mobile eye-tracking glasses in a standardized diagnostic setting while applying the Autism Diagnostic Observation Schedule (ADOS-2), we had the opportunity to record gaze behavior of children and adolescents with and without Autism Spectrum Conditions (ASCs) during social interaction. The objective was to investigate differences in eye-gaze behavior between three groups of children and adolescents either (1) with ASC or (2) with unconfirmed diagnosis of ASC or (3) with neurotypical development (NTD) during social interaction with an adult interviewer in a diagnostic standard situation using the ADOS-2. In a case control study, we used mobile eye-tracking glasses in an ecologically valid and highly standardized diagnostic interview to investigate suspected cases of ASC. After completion of the ASC diagnostic gold standard including the ADOS-2, the participants were assigned to two groups based on their diagnosis (ASC vs. non-ASC) and compared with a matched group of neurotypically developed controls. The primary outcome measure is the percentage of total dwell times assessed for different areas of interest (AOI) with regard to the face and body of a diagnostic interviewer and the surrounding space. Overall, 65 children and adolescents within an age range of 8.3-17.9 years were included in the study. The data revealed significant group differences, especially in the central-face area. Previous investigations under laboratory conditions gave preferential attention to the eye region during face perception to describe differences between ASC and NTD. In this study - using an ecologically valid setting within a standard diagnostic procedure - the results indicate that neurotypically developed controls seem to process faces and facial expressions in a holistic manner originating from the central-face region. Conversely, participants on the Autism Spectrum (tAS) seem to avoid the central-face region and show unsystematic gaze behavior, not using the preferred landing position in the central-face region as the Archimedean point of face perception. This study uses a new approach, and it will be important to replicate these preliminary findings in future research.