Exploring sensory phenotypes in autism spectrum disorder

Background: Atypical reactions to the sensory environment are often reported in autistic individuals, with a high degree of variability across the sensory modalities. These sensory differences have been shown to promote challenging behaviours and distress in autistic individuals and are predictive of other functions including motor, social, and cognitive abilities. Preliminary research suggests that specific sensory differences may cluster together within individuals creating discrete sensory phenotypes. However, the manner in which these sensory differences cluster, and whether the resulting phenotypes are associated with specific cognitive and social challenges is unclear. Methods: Short sensory profile data from 599 autistic children and adults between the ages of 1 and 21 years were subjected to a K-means cluster analysis. Analysis of variances compared age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder across the resultant clusters. Results: A five-cluster model was found to minimize error variance and produce five sensory phenotypes: (1) sensory adaptive, (2) generalized sensory differences, (3) taste and smell sensitivity, (4) under-responsive and sensation seeking, and (5) movement difficulties with low energy. Age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder were found to differ significantly across the five phenotypes. Limitations: The results were based on parent-report measures of sensory processing, adaptive behaviour, traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder, which may limit the generalizability of the findings. Further, not all measures are standardized, or psychometrically validated with an autism population. Autistic individuals with an intellectual disability were underrepresented in this sample. Further, as these data were obtained from established records from a large provincial database, not all measures were completed for all individuals. Conclusions: These findings suggest that sensory difficulties in autistic individuals can be clustered into sensory phenotypes, and that these phenotypes are associated with behavioural differences. Given the large degree of heterogeneity in sensory difficulties seen in the autistic population, these sensory phenotypes represent an effective way to parse that heterogeneity and create phenotypes that may aid in the development of effective treatments and interventions for sensory difficulties

Effects of age and symptomatology on cortical thickness in autism spectrum disorders

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours. © 2012 Elsevier Ltd. All rights reserved

Atypical functional connectivity during unfamiliar music listening in children with autism

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula.Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning.info:eu-repo/semantics/publishedVersio

Effects of Metformin on Spatial and Verbal Memory in Children with ASD and Overweight Associated with Atypical Antipsychotic Use

Abstract Objectives: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. Methods: We studied the effects of metformin (Riomet®) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management. Phase 1 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group comparison of metformin (500–850 mg given twice a day) versus placebo. During Phase 2, all participants took open-label metformin from week 17 through week 32. We assessed spatial and verbal memory using the Neuropsychological Assessment 2nd Edition (NEPSY–II) and a modified children's verbal learning task. Results: No measures differed between participants randomized to metformin versus placebo, at either 16 or 32 weeks, after adjustment for multiple comparisons. Sixteen-week change in memory for spatial location on the NEPSY–II was nominally better among participants randomized to placebo. However, patterns of treatment response across all measures revealed no systematic differences in performance, suggesting that metformin had no effect on spatial or verbal memory in these children. Conclusions: Although further study is needed to support these null effects, the overall impression is that metformin does not affect memory in overweight youth with ASD who were taking atypical antipsychotic medications

Rigor in science and science reporting: updated guidelines for submissions to Molecular Autism.

International audienceno abstrac

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions

BackgroundHeterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.MethodsUsing a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups.ResultsClustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup.LimitationsNotable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.ConclusionsConcomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

International audienc

Impaired Structural Connectivity of Socio-Emotional Circuits in Autism Spectrum Disorders: A Diffusion Tensor Imaging Study

Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD.DTI scans were acquired for 19 children and adolescents with ASD (∼8-18 years; mean 12.4±3.1) and 16 age and IQ matched controls (∼8-18 years; mean 12.3±3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (≤12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing.Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder

Is inhibitory control a ‘no-go’ in adolescents with autism spectrum disorder?

Abstract Background Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents. Methods The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200 ms to 400 ms post-stimulus onset. Significant activations were determined using permutation testing. Results Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250 ms) followed by the left postcentral gyrus (250 to 300 ms) and finally the left middle frontal and right medial frontal gyri (300 to 400 ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250 ms), followed by the left superior and inferior frontal gyri (250 to 300 ms), then the right middle temporal gyrus (300 to 350 ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400 ms). Conclusions Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls