Diagnostic Observation Research Articles

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit.

Disturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied. To investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD). This cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. Participants in MARBLES were recruited through the UC Davis MIND Institute. This subset of the MARBLES cohort included younger siblings born between 2009 and 2015. Maternal third trimester serum, placental tissue, and umbilical cord serum samples were collected from participants. Only pregnancies with at least 2 of these sample types were included in this analysis. Data analysis was conducted from March 1, 2023, to March 15, 2024. Quantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery. Using the Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning, outcomes were classified as ASD, other nontypical development (non-TD), and typical development (TD). This analysis included 100 maternal serum samples, 141 placental samples, and 124 umbilical cord serum samples from 152 pregnancies (median [IQR] maternal age, 34.6 [30.8-38.3] years; median [IQR] gestational age, 39.0 [38.6-39.7] weeks; 87 [57.2%] male infants). There was no evidence that the maternal third trimester serum metabolome was significantly associated with the other metabolomes. The placental and cord serum metabolomes were highly correlated (first latent variate pair: R2 = 0.75; P < .001) and the variate scores for each tissue were significantly associated with reduced risk of non-TD (placenta: relative risk [RR], 0.13; 95% CI, 0.02-0.71; cord: RR, 0.13; 95% CI, 0.03-0.70) but not ASD (placenta: RR, 1.09; 95% CI, 0.42-2.81; cord: RR, 0.63; 95% CI, 0.23-1.73) compared with the TD reference group. In this cohort study of children with high familial risk of ASD, placental and cord serum metabolism at delivery were highly correlated. Furthermore, placental and cord serum metabolic profiles were associated with risk of non-TD.

Social communication and restricted, repetitive behavior as assessed with a diagnostic tool for autism (ADOS-2) in women with anorexia nervosa.

In anorexia nervosa (AN), the traits of autism spectrum disorder (ASD) are associated with poor outcomes. However, the subtle nature of these characteristics remains poorly understood. We investigated the in-depth patterns of ASD traits using Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) in women with AN. Of 28 women with ICD-10 AN, 16 (age 19-30 years) participated in the ADOS-2, a video-recorded, semistructured diagnostic assessment for social communication and interaction and restricted, repetitive behaviors and interests related to ASD. None of the participants had previously been diagnosed with ASD. Other measurements included the Eating Disorder Examination Questionnaire and the Wechsler Abbreviated Scale of Intelligence-IV. Five individuals (18% of all, 31% of those assessed) scored above the cutoff for autism in ADOS-2. They had challenges in social communication and interaction, manifesting as sustained difficulties in social relationships and deficits in conversation skills. Few described being frequently misunderstood by others, including in the eating disorder treatment settings. Three individuals showed prominent restricted and repetitive behaviors such as ritual seeking, eating-related routines, sensory sensitivity related to food texture and selective eating, and intense interest in specific topics. The mean duration of AN in women above the cutoff was twice as long compared with those below (12.3 vs. 6.2 years). The ASD-related characteristics and behavior appear to contribute to the manifestation and duration of AN in a subgroup of women. Among these women, the traits of ASD appear to be mixed with eating disorder symptoms, which should be taken into account in the treatment.

Abnormality of Early White Matter Development in Tuberous Sclerosis Complex and Autism Spectrum Disorder: Longitudinal Analysis of Diffusion Tensor Imaging Measures.

Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n = 78. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = 0.0093, P = .0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = -0.00002071, P = .0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models.

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

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. 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. 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). 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.

Association of Breastfeeding Duration with Neurodevelopmental Outcomes in an Enriched Familial Likelihood Cohort for Autism Spectrum Disorder.

This study aimed to compare the breastfeeding (BF) duration of the younger siblings of children with ASD in an enriched-likelihood cohort for autism spectrum disorder (ASD), and to determine whether longer BF duration was associated with differences in neurodevelopmental outcomes in this cohort. Information on BF practices was collected via surveys in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. Developmental evaluations, including the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, were conducted by expert clinicians. Participants' neurodevelopmental outcome was classified by an algorithm into three groups: typical development, ASD, and non-typical development. The median duration of BF was 10.70months (interquartile range of 12.07months). There were no significant differences in the distribution of duration of BF among the three neurodevelopmental outcome categories. Children in this enriched-likelihood cohort who were breastfed for > 12months had significantly higher scores on cognitive testing compared to those who were breastfed for 0-3months. There was no significant difference in ASD symptomatology or ASD risk based on BF duration.

Analyzing the Quality of Life in Individuals with Fragile X Syndrome in Relation to Sleep and Mental Health.

The purpose of this paper was to examine the physical, emotional, social and school functioning domains of quality of life of individuals with Fragile X Syndrome, in relation to mental health and sleep patterns to gain a better understanding of how these aspects are affected by the disorder. This study included 119 individuals with Fragile X Syndrome who were given different cognitive examinations by a neuropsychologist or by parent-proxy questionnaires. This study focused on the Pediatric Quality of Life Inventory (PedsQoL), the Anxiety, Depression and Mood Scale (ADAMS), the Children's Sleep Habits Questionnaire (CSHQ), but did include other cognitive tests (Vineland Adaptive Behaviour Scales, Nonverbal IQ, Autism Diagnostic Observation Schedule). We identified significant associations between decreases in emotional, social and school domains of PedsQoL and the ADAMS subtests of Generalized Anxiety, Manic/Hyperactivity and Obsessive/Compulsivity, with the subtest of Depressed Mood having associations with lower physical and emotional domains. We also identified a significant impact between CSHQ subtests of Sleep Anxiety, Night Wakings, Daytime Sleepiness, and Parasomnia with the emotional and school domains of PedsQoL. There were associations connecting school functioning with Bedtime Resistance, and additional associations connecting emotional functioning with Sleep Duration and Sleep Onset Delay. Physical functioning was also associated with Sleep Anxiety. Our study shows how mental health and sleep defects impact improper sleep patterns and mental health which leads to decreases in the quality of life for individuals with FXS, and how it is important to screen for these symptoms in order to alleviate issues.

Predicting individual autistic symptoms for patients with autism spectrum disorder using interregional morphological connectivity

Intelligent predictive models for autistic symptoms based on neuroimaging datasets were beneficial for the precise intervention of patients with ASD. The goals of this study were twofold: investigating predictive models for autistic symptoms and discovering the brain connectivity patterns for ASD-related behaviors. To achieve these goals, we obtained a cohort of patients with ASD from the ABIDE project. The autistic symptoms were measured using the Autism Diagnostic Observation Schedule (ADOS). The anatomical MRI datasets were preprocessed using the Freesurfer package, resulting in regional morphological features. For each individual, the interregional morphological network was constructed using a novel feature distance-based method. The predictive models for autistic symptoms were built using the support vector regression (SVR) algorithm with feature selection method. The predicted autistic symptoms (i.e., ADOS social score, ADOS behavior) were significantly correlated to the original measures. The most predictive features for ADOS social scores were located in the bilateral fusiform. The most predictive features for ADOS behavior scores were located in the temporal pole and the lingual gyrus. In summary, the autistic symptoms could be predicted using the interregional morphological connectivity and machine learning. The interregional morphological connectivity could be a potential biomarker for autistic symptoms.

Prenatal perceived stress and urinary cortisol as risk factors for ASD and non-typical developmental outcomes in the MARBLES study

BackgroundFindings for prenatal stress, previously measured through stressful life event surveys items or biomarkers, in association with ASD are inconsistent. We prospectively examined prenatal perceived stress and prenatal urinary cortisol (PUC) in association with ASD and other non-typical developmental (Non-TD) outcomes in the child in a high familial likelihood cohort. MethodsThe Perceived Stress Scale questionnaire was used to measure perceived stress in the longitudinal Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) Study. Cortisol was measured through 24-hr urine collections. At three years of age, an algorithm consisting of scores from the Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL) was used to classify children with ASD, Non-TD, or typically developing (TD) outcomes. Relative risk ratios (RRR) with TD as the reference were estimated using multinomial logistic regression. ResultsIncreased perceived stress was associated with Non-TD in trimester 1 (RRR 1.10; 95% CI: 1.00, 1.21) and ASD in trimesters 2 and 3 (RRR 1.08; 95% CI: 1.02, 1.14 and RRR 1.08; 95% CI: 1.03, 1.14, respectively). Results with PUC were non-significant but were in the direction consistent with previous findings suggesting that decreased cortisol levels are associated with higher likelihood of ASD. ConclusionsFindings support the hypothesis that higher perceived stress is associated with increased likelihood of ASD and possibly Non-TD, relative to TD. This suggests that stress reduction interventions during pregnancy could serve as preventative measures that help optimize the child’s long-term health. Larger studies are needed to replicate these findings.

Clinician Opinions Regarding the Usefulness of the BOSA for ASD Assessment in a Service for Children Aged Under 12 Years.

The COVID-19 pandemic and the subsequent social distancing policies forced healthcare teams to drastically alter the way they deliver services. This was particularly challenging for clinicians involved in diagnosing autism spectrum disorder (ASD), as assessment tools and methods required face-to-face social interactions between clinicians and children. To address this, the Brief Observation of Symptoms of Autism (BOSA) was developed to ensure that people suspected of ASD can receive diagnostic assessments during the pandemic. This project aimed to explore clinicians' opinions on the BOSA, particularly regarding the usefulness of the assessment for clinicians to clarify diagnostic outcomes of ASD assessments. Both quantitative and qualitative data was gathered within an NHS community paediatric team. This included a questionnaire for clinicians to complete, and data from the BOSA assessments done in the service. Thematic analysis and descriptive statistics revealed that many clinicians felt that the BOSA can be beneficial in certain cases, such as selective mutism, and found the BOSA particularly helpful for observing parent-child interactions. These findings highlighted important information that the Autism Diagnostic Observation Schedule Second Edition (ADOS-2) does not give opportunities to observe. Clinicians reported that at times, the BOSA materials, brevity and parental administration created barriers to gathering information for diagnostic decisions. As may be expected, clinicians showed a clear preference for the more familiar and validated ADOS-2. However, the study highlights perceived limitations of the ADOS-2 and strengths of the BOSA, with recommendations made for future practice and research.

A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study.

Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Children aged 6-12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p = .02), (F(4, 93) = 3.185, p = .017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p = .211). Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut-microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

Title: Misdiagnosis in young females – Autism versus Borderline Personality Disorders

IntroductionThe diagnostic overlap between Autism Spectrum Disorder (ASD) and Emotionally Unstable Personality Disorder (EUPD), commonly referred to as Borderline Personality Disorder (BPD), presents a considerable challenge in psychiatric practice, particularly for young females. These complexities are amplified by gender biases in the healthcare system and can lead to misdiagnosis, affecting both treatment planning and long-term outcomes.ObjectivesThere are differences and similarities between ASD and EUPD/BPD which encompass its own challenges in diagnosis and treatmentThe presentation seeks to: 1.Offer an in-depth overview of the relationship between ASD and EUPD/BPD in young females.2.Evaluate the diagnostic challenges associated with distinguishing between these two conditions.3.Discuss the practical implications of misdiagnosis on treatment and quality of life. MethodsDrawing from a rich corpus of evidence, including longitudinal studies (e.g., Kerns et al., 2015; Gunderson et al., 2018), meta-analyses, and patient case studies, the presentation adopts a multidisciplinary approach. It utilises clinical interviews, validated diagnostic tools such as the Autism Diagnostic Observation Schedule (ADOS) and the Structured Clinical Interview for DSM-5 (SCID-5), as well as direct observation to provide a nuanced understanding of ASD and EUPD/BPD characteristics.ResultsShared Characteristics: Both ASD and EUPD/BPD manifest challenges in social functioning and mood regulation, supported by studies indicating sensory sensitivities and affective dysregulation in both conditions (Zanarini et al., 2019; Happé et al., 2019).Differentiating Factors: ASD individuals often struggle with verbal and non-verbal communication, whereas those with EUPD/BPD may excel in these areas but display emotional volatility and unstable relationships, substantiated by differing neurobiological markers (King-Casas et al., 2008; Minshew &amp; Williams, 2007).Misdiagnosis Risks: The failure to correctly diagnose these conditions may lead to ineffective or potentially harmful treatment plans (Zanarini et al., 2013; Solomon et al., 2012).Necessity for Comprehensive Assessment: A multimodal and culturally sensitive diagnostic approach is essential for accurate clinical evaluation (Mandy et al., 2012; Betancur et al., 2009).ConclusionsThe complexities surrounding the accurate diagnosis of ASD and EUPD/BPD in young females necessitate a thorough and multifaceted approach. An incorrect diagnosis could have long-lasting implications, affecting not just the efficacy of therapeutic interventions but also the overall well-being and quality of life of the individual. This presentation underscores the critical importance of drawing from a robust body of evidence and utilising comprehensive diagnostic approaches to differentiate these conditions.Disclosure of InterestNone Declared

Comparative analysis of self-stimulatory behaviors in ASD and ADHD

IntroductionThe phenomenon of self-stimulatory behaviors, commonly referred to as “stimming,” presents a fascinating avenue of exploration within the context of neurodevelopmental disorders. While stimming behaviors are widely associated with ASD, there is emerging evidence suggesting that individuals with ADHD may also engage in similar behaviors. This study seeks to undertake a comprehensive investigation of the neurophenomenology of stimming in individuals diagnosed with ASD and ADHD, aiming to discern potential shared and distinctive characteristics.Objectives The principal objective of this research is to conduct an intricate neurophenomenological analysis of stimming behaviors in cohorts diagnosed with ASD (n=60) and ADHD (n=60), with a concurrent control group of neurotypical individuals (n=60). The study aspires to delineate the prevalence, typology, and neurophysiological underpinnings of stimming behaviors in both ASD and ADHD populations. Moreover, this study endeavors to identify whether particular stimming behaviors exhibit differential prevalence or intensity between the two disorders.MethodsParticipants underwent rigorous neurophenomenological assessments, incorporating structured interviews, validated self-report questionnaires and direct observations. Diagnostic confirmation was established through the administration of gold-standard instruments, such as the Autism Diagnostic Observation Schedule (ADOS-2) for ASD and the Conners’ Parent Rating Scale for ADHD. Stimming behaviors were meticulously categorized (e.g., motor, vocal, sensory) and scrutinized for quantitative metrics, including frequency, duration, and complexity.Results Preliminary analyses have uncovered profound disparities in the manifestation of stimming behaviors between ASD and ADHD cohorts. Individuals with ASD displayed a significantly higher prevalence of stimming behaviors, with motor stimming predominating, followed by vocal and sensory manifestations. In contrast, individuals with ADHD exhibited a comparatively reduced frequency and intensity of stimming, primarily within the motor domain, albeit notably less elaborate. Control group participants exhibited a negligible occurrence of stimming behaviors.ConclusionsThis multidimensional exploration illuminates the nuanced neurophenomenological distinctions in self-stimulatory behaviors between ASD and ADHD. Stimming emerges as a pivotal feature in ASD, while its presence in ADHD, though discernible, is markedly attenuated. This study’s findings hold implications for precise diagnostic delineation and the prospect of personalized interventions for these complex neurodevelopmental conditions. Future avenues of research may delve into the neural substrates underpinning stimming behaviors, further enhancing our comprehension of these phenomena.Disclosure of InterestNone Declared

A Direct Comparison of Three Screening Methods for Autism Spectrum Disorder in a High-Likelihood Sibling Population.

Targeted screening of children at increased likelihood of autism is recommended. However, autism screening tools are usually validated for use mainly in low-likelihood populations. This study compared the accuracy of the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F), the ASDetect app, and the Social Attention and Communication Surveillance, Revised (SACS-R). Siblings of autistic children underwent autism screening at 12, 18 and 30months old. At each visit, caregivers completed the M-CHAT-R/F and ASDetect while trained nurses tested the siblings using the SACS-R. At 36 to 48months, the siblings underwent an Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) assessment. 189 siblings were screened, 141 completed the study, and 32 were confirmed to have autism. Although not validated for use at 12months, the M-CHAT-R/F had the best sensitivity among the three tools for this age group, suggesting that early signs are already apparent to caregivers. The M-CHAT-R/F had overall better sensitivity (0.72-0.83) across all age groups, but with overall lower specificity (0.55-0.77). The SACS-R and ASDetect had better positive predictive values at 18 and 30months (0.60-0.68), while the M-CHAT-R/F was 0.43-0.48. Negative predictive values were generally high across all three tools across all age groups (0.78-0.93). Targeted screening of children at high likelihood of autism yielded a detection rate of 22.7% and should therefore be implemented routinely to facilitate early detection and intervention. The performance of autism screening tools should be examined in higher-likelihood populations for targeted screening of these children.

Biomarkers of preschool children with autism spectrum disorder: quantitative analysis of whole-brain tissue component volumes, intelligence scores, ADOS-CSS, and ages of first-word production and walking onset.

Preschooling is a critical time for intervention in children with autism spectrum disorder (ASD); thus, we analyzed brain tissue component volumes (BTCVs) and clinical indicators in preschool children with ASD to identify new biomarkers for early screening. Eighty preschool children (3-6 years) with ASD were retrospectively included. The whole-brain myelin content (MyC), white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging (SyMRI). Clinical data, such as intelligence scores, autism diagnostic observation schedule-calibrated severity scores, age at first production of single words (AFSW), age at first production of phrases (AFP), and age at walking onset (AWO), were also collected. The correlation between the BTCV and clinical data was evaluated, and the effect of BTCVs on clinical data was assessed by a regression model. WM and GM volumes were positively correlated with intelligence scores (both P < 0.001), but WM and GM did not affect intelligence scores (P = 0.116, P = 0.290). AWO was positively correlated with AFSW and AFP (both P < 0.001). The multivariate linear regression analysis revealed that MyC, AFSW, AFP, and AWO were significantly different (P = 0.005, P < 0.001, P < 0.001). This study revealed positive correlations between WM and GM volumes and intelligence scores. Whole-brain MyC affected AFSW, AFP, and AWO in preschool children with ASD. Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker (abnormal MyC) for early ASD screening in preschool children.

Assessment of Psychotic Risk in a Sample of Children and Adolescents with Autism Spectrum Disorder Compared to a Group of "Clinical High Risk" Patients: A Preliminary Study.

Autism spectrum disorder and psychotic risk show several overlapping symptoms, so differential diagnosis is often difficult. In addition, there is a high rate of comorbidity between the two conditions, which further complicates the work of clinicians. We evaluated the presence of subthreshold psychotic symptoms and/or defined psychotic risk syndromes in autistic children and adolescents; we compared the prevalence, type, and severity of psychotic risk symptoms with those of a group of non-autistic patients at clinical high risk for psychosis (CHR-P). 2. In total, 23 autistic patients and 14 CHR-P patients without autism (aged 8-17) were enrolled in the study. The main assessment was made through clinical interviews for autism (Autism Diagnostic Observation Schedule, Second Edition-ADOS-2, Autism Diagnostic Interview, Revised-ADI-R) and psychotic risk (Schizophrenia Proneness Instrument, Child and Youth version-SPI-CY, Structured Interview for Psychosis Risk Syndromes-SIPS). 3. No above-threshold psychotic risk symptoms were detected in our autistic patients, but subthreshold psychotic symptoms were identified in all areas. Specific items from all four dimensions of SIPS appear to be more specific for psychotic risk than autism without comorbidity. 4. An a priori screening of psychotic risk in neurodiverse populations is fundamental to prevent more severe conditions. Research should clarify the effective specificity of the available tools to modify them to improve their detection capability.

A Preliminary Trial of an Early Surveillance Program for Autism and Developmental Delays within General Practices

AbstractThere are inequities in engagement with established early childhood developmental surveillance programs, eclipsing disadvantaged families. The current study sought to address this by dovetailing developmental surveillance with immunization visits and other opportunistic contacts with children at general practices). While 53 General Practices were recruited, significant COVID-19 disruptions resulted in only 81 children being screened (both parent-administered and GP completed). Of the 81 children, 11 screened positive and all of them along with 5% of screen negatives (i.e. 4 children) received clinician-administered reference-standard assessment for autism and developmental delay (DD) using Autism Diagnostic Observation Schedule (ADOS), Autism Diagnostic Interview Schedule –Revised (ADI-R), and Mullen Scales of Early Learning (MSEL). All children found by reference-standard assessment to have probable autism and/or DD had screened positive during the screening process, and 90.9% of children who screened positive were found by reference-standard assessment to have probable DD or autism. The findings provide early evidence for the feasibility and usefulness of parent completed and GP administered developmental measures during opportunistic contacts with GPs as a promising method to facilitate early identification of DD or autism.

Improved emotion differentiation under reduced acoustic variability of speech in autism

BackgroundSocio-emotional impairments are among the diagnostic criteria for autism spectrum disorder (ASD), but the actual knowledge has substantiated both altered and intact emotional prosodies recognition. Here, a Bayesian framework of perception is considered suggesting that the oversampling of sensory evidence would impair perception within highly variable environments. However, reliable hierarchical structures for spectral and temporal cues would foster emotion discrimination by autistics.MethodsEvent-related spectral perturbations (ERSP) extracted from electroencephalographic (EEG) data indexed the perception of anger, disgust, fear, happiness, neutral, and sadness prosodies while listening to speech uttered by (a) human or (b) synthesized voices characterized by reduced volatility and variability of acoustic environments. The assessment of mechanisms for perception was extended to the visual domain by analyzing the behavioral accuracy within a non-social task in which dynamics of precision weighting between bottom-up evidence and top-down inferences were emphasized. Eighty children (mean 9.7 years old; standard deviation 1.8) volunteered including 40 autistics. The symptomatology was assessed at the time of the study via the Autism Diagnostic Observation Schedule, Second Edition, and parents’ responses on the Autism Spectrum Rating Scales. A mixed within-between analysis of variance was conducted to assess the effects of group (autism versus typical development), voice, emotions, and interaction between factors. A Bayesian analysis was implemented to quantify the evidence in favor of the null hypothesis in case of non-significance. Post hoc comparisons were corrected for multiple testing.ResultsAutistic children presented impaired emotion differentiation while listening to speech uttered by human voices, which was improved when the acoustic volatility and variability of voices were reduced. Divergent neural patterns were observed from neurotypicals to autistics, emphasizing different mechanisms for perception. Accordingly, behavioral measurements on the visual task were consistent with the over-precision ascribed to the environmental variability (sensory processing) that weakened performance. Unlike autistic children, neurotypicals could differentiate emotions induced by all voices.ConclusionsThis study outlines behavioral and neurophysiological mechanisms that underpin responses to sensory variability. Neurobiological insights into the processing of emotional prosodies emphasized the potential of acoustically modified emotional prosodies to improve emotion differentiation by autistics.Trial registrationBioMed Central ISRCTN Registry, ISRCTN18117434. Registered on September 20, 2020.

Maternal preconception and prenatal stressful life events in association with child neurodevelopmental outcome in MARBLES: A high familial likelihood cohort

BackgroundPrenatal stressful life events (SLEs) have been inconsistently associated with autism spectrum disorder (ASD). Mothers who are already raising a child with ASD could experience compounding effects of prenatal SLEs. This study prospectively examined prenatal SLEs in association with child neurodevelopmental outcomes in a high familial likelihood cohort. MethodsParticipants were 317 mother-child pairs from the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) Study, where pregnant women have previously had at least one other child with ASD. Mothers were interviewed during and at the end of pregnancy about whether they had experienced any of 7 SLE categories relating to finance, marriage, death, and more.Child neurodevelopment at three years old was classified as typically developing (TD), Non-TD, or ASD using an algorithm applied to Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) scores. Relative risk ratios (RRR) with TD as the reference outcome were estimated using multinomial logistic regression. ResultsExperiencing legal problems was significantly associated with an increased relative risk of child Non-TD (RRR 3.75; 95% CI: 1.15, 12.22). However, this finding was based on a small sample size (n = 6) and should be interpreted with caution. All other associations with Non-TD and ASD were non-significant. ConclusionsFindings agree with previous literature suggesting prenatal SLEs might not increase likelihood for ASD and most were not associated with Non-TD. Future studies measuring perceived stress or stress biomarkers are warranted to further understand the true association of prenatal stress and likelihood of ASD.

Sex differences in autism screening: An examination of the Childhood Autism Spectrum Test-Hebrew version.

Autism is a neurodevelopmental condition, characterized by social communication alterations and restricted, repetitive behaviors. Typically diagnosed in early childhood, screening and diagnosis at a later age can be challenging, particularly in girls who exhibit a wider range of behaviors and characteristics. Our study set out to examine the effectiveness of the Hebrew translation of the Childhood Autism Spectrum Test, a parent report questionnaire, in identifying these diverse characteristics of autism within an Israeli sample of boys and girls. We examined parent reports on 403 (211 autistic, 192 non-autistic) children, aged 4-12 years. Results revealed the Childhood Autism Spectrum Test-Hebrew version was a valuable tool in differentiating between autistic and typically developing children, correctly identifying 93% of children with autism and 82% of typically developing children. In addition, specific items of the Childhood Autism Spectrum Test-Hebrew version were particularly useful in differentiating between autistic and non-autistic boys and autistic and non-autistic girls. Using these items, in addition to the overall score of the questionnaire, increased the correct identification of children as autistic or typically developing, especially in girls. The Childhood Autism Spectrum Test-Hebrew version test results corresponded well with the Autism Diagnostic Interview-Revised, which relies on parental input, but not with the clinician-administered Autism Diagnostic Observation Schedule-2. Our findings highlight the potential benefits of gender-specific tools to better support correct identification of autism in boys and in girls. More research is recommended to further explore these gender differences and to validate our findings with a larger, diverse group.

Classifying autism in a clinical population based on motion synchrony: a proof-of-concept study using real-life diagnostic interviews

Predictive modeling strategies are increasingly studied as a means to overcome clinical bottlenecks in the diagnostic classification of autism spectrum disorder. However, while some findings are promising in the light of diagnostic marker research, many of these approaches lack the scalability for adequate and effective translation to everyday clinical practice. In this study, our aim was to explore the use of objective computer vision video analysis of real-world autism diagnostic interviews in a clinical sample of children and young individuals in the transition to adulthood to predict diagnosis. Specifically, we trained a support vector machine learning model on interpersonal synchrony data recorded in Autism Diagnostic Observation Schedule (ADOS-2) interviews of patient-clinician dyads. Our model was able to classify dyads involving an autistic patient (n = 56) with a balanced accuracy of 63.4% against dyads including a patient with other psychiatric diagnoses (n = 38). Further analyses revealed no significant associations between our classification metrics with clinical ratings. We argue that, given the above-chance performance of our classifier in a highly heterogeneous sample both in age and diagnosis, with few adjustments this highly scalable approach presents a viable route for future diagnostic marker research in autism.