1. Barami T, Manelis-Baram L, Kaiser H, Ilan M, Slobodkin A, Hadashi O, Hadad D, Waissengreen D, Nitzan T, Menashe I, Michaelovsky A, Begin M, Zachor DA, Sadaka Y, Koler J, Zagdon D, Meiri G, Azencot O, Sharf A, Dinstein I. Automated Analysis of Stereotypical Movements in Videos of Children With Autism Spectrum Disorder. JAMA Netw Open;2024 (Sep 3);7(9):e2432851.

IMPORTANCE: Stereotypical motor movements (SMMs) are a form of restricted and repetitive behavior, which is a core symptom of autism spectrum disorder (ASD). Current quantification of SMM severity is extremely limited, with studies relying on coarse and subjective caregiver reports or laborious manual annotation of short video recordings. OBJECTIVE: To assess the utility of a new open-source AI algorithm that can analyze extensive video recordings of children and automatically identify segments with heterogeneous SMMs, thereby enabling their direct and objective quantification. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 241 children (aged 1.4 to 8.0 years) with ASD. Video recordings of 319 behavioral assessments carried out at the Azrieli National Centre for Autism and Neurodevelopment Research in Israel between 2017 and 2021 were extracted. Behavioral assessments included cognitive, language, and autism diagnostic observation schedule, 2nd edition (ADOS-2) assessments. Data were analyzed from October 2020 to May 2024. EXPOSURES: Each assessment was recorded with 2 to 4 cameras, yielding 580 hours of video footage. Within these extensive video recordings, manual annotators identified 7352 video segments containing heterogeneous SMMs performed by different children (21.14 hours of video). MAIN OUTCOMES AND MEASURES: A pose estimation algorithm was used to extract skeletal representations of all individuals in each video frame and was trained an object detection algorithm to identify the child in each video. The skeletal representation of the child was then used to train an SMM recognition algorithm using a 3 dimensional convolutional neural network. Data from 220 children were used for training and data from the remaining 21 children were used for testing. RESULTS: Among 319 behavioral assessment recordings from 241 children (172 [78%] male; mean [SD] age, 3.97 [1.30] years), the algorithm accurately detected 92.53% (95% CI, 81.09%-95.10%) of manually annotated SMMs in our test data with 66.82% (95% CI, 55.28%-72.05%) precision. Overall number and duration of algorithm-identified SMMs per child were highly correlated with manually annotated number and duration of SMMs (r = 0.8; 95% CI, 0.67-0.93; P < .001; and r = 0.88; 95% CI, 0.74-0.96; P < .001, respectively). CONCLUSIONS AND RELEVANCE: This study suggests the ability of an algorithm to identify a highly diverse range of SMMs and quantify them with high accuracy, enabling objective and direct estimation of SMM severity in individual children with ASD.

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2. Bartholomay KL, Lightbody AA, Ma Q, Jo B, Jordan TL, Reiss AL. Cognitive and Social-Emotional Development in Girls With Fragile X Syndrome. Pediatrics;2024 (Sep 12)

OBJECTIVES: To evaluate the developmental trajectory of key cognitive, social, and emotional features in girls with fragile X syndrome (FXS). METHODS: This longitudinal, parallel cohort study collected data between January 2018 and December 2022. Participants were evaluated 3 times with ∼12-18 months between visits. Participants included 65 girls with FXS, 6 to 16 years, and 52 age- and developmentally-matched girls without FXS. Participants’ scores from direct assessment and caregiver report evaluated 3 cognitive domains (verbal abilities, nonverbal abilities, executive function) and 4 social-emotional domains (depression, general anxiety, social behavior, and social anxiety). RESULTS: Participants included 117 girls (mean [M] [SD] age at study entry: FXS M = 10.59 [3.00]; comparison M = 10.45 [2.40])). Omnibus tests showed 4 domains with significant group differences: Verbal (P < .0001, eg, Differential Abilities Scale-II(DAS-II), Picture Vocabulary (-6.25 [1.87])), nonverbal (P < .0001, eg, Kaufman Test of Educational Achievement, Third Edition, Brief Form, Math (-8.56 [2.90])), executive function (P < .0001, eg, NIH Toolbox List Sorting (-6.26 [1.48])), and social anxiety (P < .03, eg, Anxiety, Depression, and Mood Scale (ADAMS) Social Avoidance (1.50 [0.65])). Three domains had significant group by age interaction: Verbal (P < .04, eg, DAS-II, Word Definitions (-1.33 [0.55])), social behavior (P < .01, eg, Social Responsiveness Scale-2 Social Communication (1.57 [0.51])), and social anxiety (P < .01, eg, ADAMS Social Avoidance (0.46 [0.19])). CONCLUSIONS: These findings support the development of early, disorder specific interventions for girls with FXS targeting verbal and nonverbal skills, executive function, social behavior, and social anxiety.

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3. Bertelli MO, Bianco A, Deb S, Scuticchio D, Kaleci S, Scattoni ML. Autism and psychopathology – prevalence, identification, and symptoms equivalence: study protocol. Front Psychiatry;2024;15:1447262.

OBJECTIVE: Despite increasing evidence of high psychopathological vulnerability in people with Autism Spectrum Disorder (ASD) and/or Intellectual disability (ID), comprehensive data on prevalence and presentation of psychiatric disorders (PD) in people with significant cognitive and communication impairment are lacking. The extent to which PD can present with behavioral/observable symptoms and include Problem Behaviors (PB) has also been scarcely evaluated through population-based studies. The paper presents the protocol of a cross-sectional study aimed at filling these gaps, referred to a large multicentric Italian population-based sample of adolescents and adults. METHODS: A battery of validated scales, SPAIDD, DASH-II, DiBAS-R, and STA-DI, is used to support and control for clinical diagnoses of PD. Study population is stratified according to different independent variables such as the severity of ID and ASD, gender, age group, and source of recruitment. A network analysis will be carried out to identify the most central behavioral symptoms for the various PD and their relationship with PB. Overlap between psychiatric symptoms and ASD and ID phenotypes is also addressed. RESULTS AND CONCLUSION: This study should provide valuable insight into better diagnostic accuracy, leading to well-informed interventions to improve the quality of life of people with ASD and/or ID.

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4. David N, Rahlff P, König H, Dückert S, Gewohn P, Erik F, Vogeley K, Schöttle D, Konnopka A, Schulz H, Peth J. Barriers to healthcare predict reduced health-related quality of life in autistic adults without intellectual disability. Autism;2024 (Sep 11):13623613241275406.

Health-related quality of life reflects a person’s perspective on their well-being in physical, mental, social, work-related, and other aspects of health or life. Autistic adults typically report difficulties in many or all of these domains and, thus, often experience their health-related quality of life being reduced. Nonetheless, they do not obtain the professional support they need and report barriers to accessing or receiving appropriate healthcare. We know little about the impact of barriers to healthcare on health-related quality of life in autistic adults. In the present study, 311 autistic adults without intellectual disability in Germany completed an online survey on their current health-related quality of life and the number of barriers to healthcare they experience. In addition, they were asked about their personal and clinical background as well as about the amount of healthcare and support they recently received. We investigated how this information and, particularly, barriers to healthcare explained variations in individual levels of health-related quality of life. We found that barriers to healthcare, compared to most other variables, were a strong predictor of health-related quality of life: The more barriers autistic adults reported, the lower their experienced psychological and physical well-being. To our knowledge, this is the first paper to examine the relationship between barriers to healthcare and health-related quality of life in autism. Our results suggest that healthcare providers need to become aware of the barriers individuals with autism have in seeking and getting healthcare. Improved access to services might contribute to better health-related quality of life in autistic adults.

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5. Ferman S, Segal O. The Face of Autism in Israel. Neuropsychiatr Dis Treat;2024;20:1677-1692.

This article seeks to offer a comprehensive perspective on autism in Israel, aligning with global reports. It aims to serve as a foundational resource for policymakers in developing relevant support and point to unmet needs. The data was drawn from publications by Israeli government authorities and academic publications. In 2022, the prevalence of child and adolescent autism in Israel was approximately 1.13%, with a male-to-female ratio of 4:1, and an annual increase of 23%, particularly among young children. In Israel, the diagnosis of autism follows the DSM-5 guidelines and is conducted by a physician and a psychologist specializing in autism. Typically, diagnosis is at age 2. The autism intervention approaches prevalent in Israel are consistent with those that are globally accepted. Children with autism are entitled to special education services adapted to their needs and developmental levels. The legally established package of services for children with autism includes sessions with occupational therapists, speech-language pathologists (SLPs), physical therapists, psychologists, and social workers. Children and adults with autism are eligible for disability allowance along with support regarding residence, educational programs, and employment opportunities. Nonetheless, underdiagnosis and low accessibility to services are common in minority populations and rural areas. Furthermore, in recent years, services for autistic individuals have declined. This decline, particularly considering the ongoing rise in the prevalence of autism, pose significant challenges for Israeli government authorities in ensuring that autistic persons receive appropriate support.

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6. Harbin SG, Hugh ML, Tagavi D, Bravo A, Joshi M, Kiche S, Michael OG, Locke J. In an Imperfect World: Barriers and Facilitators to Educators’ Evidence-Based Practice Use for Elementary-Aged Autistic Students in Inclusive Settings. J Autism Dev Disord;2024 (Sep 11)

Educators’ use of evidence-based practices (EBP) provides positive outcomes for autistic students in multiple areas of learning (e.g., peer interactions and academic skills) and may promote access and participation in general educational settings. However, many teachers report limited use of EBPs for their autistic students, with inconsistent fidelity. This study sought to understand barriers and facilitators educators identify to implementing EBPs with autistic students in general education classrooms. To understand educators’ perspectives and experiences, we conducted a qualitative study with 81 educators who serve elementary-aged autistic students in one state. In response to interview questions based on the Consolidated Framework for Implementation Research framework, educators reported on multiple factors, including the general education environment, access to resources, training in EBPs, and professional collaboration. Implications for practice, training, and research are discussed. Specifically, we address educators’ need for increased training and the availability of educator resources.

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7. Kaintura A, Ramar K, Sankar UG. Sympathetic Response of Children With Autism Spectrum Disorder During Dental Treatment Performed in a Sensory-Adapted Dental Environment. Cureus;2024 (Aug);16(8):e66685.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social interaction, communication, and sensory processing. These challenges often make dental visits overwhelming and distressing for children with ASD. This study explores the use of electrodermal activity (EDA) to measure physiological stress responses and evaluates strategies to enhance cooperation during dental treatments in a sensory-adapted dental environment. We conducted a case series involving three children with ASD who required dental treatment. Each child’s physiological responses to dental stimuli were monitored using EDA, which measures changes in skin conductance levels and skin conductance responses. Interventions included the use of dim lighting, the avoidance of loud noises, the application of firm pressure, the provision of sensory toys, social stories before appointments, and desensitization and video modeling techniques. All three patients exhibited phasic variations in EDA levels in response to stressful stimuli and tonic changes with calming stimuli. Case 1 responded to bright lights and unfamiliar settings with increased phasic activity, while calming stimuli like firm pressure resulted in tonic changes. Case 2 showed similar phasic responses to a weighted lap pad and tonic changes with music. Case 3 reacted to confined spaces and sudden light and touch with phasic variations and both a massager and music-induced tonic changes. Interventions were tailored to each patient’s specific stressors, resulting in improved cooperation and reduced stress levels. The study demonstrates the effectiveness of EDA as a tool for monitoring stress responses in children with ASD during dental treatments. Tailoring interventions to individual sensory needs can significantly enhance patient cooperation and comfort. These findings highlight the importance of adapting dental environments and protocols to accommodate the unique needs of children with ASD, with collaborative efforts from occupational therapists and dentists.

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8. Keysers C, Silani G, Gazzola V. Predictive coding for the actions and emotions of others and its deficits in autism spectrum disorders. Neurosci Biobehav Rev;2024 (Sep 10);167:105877.

Traditionally, the neural basis of social perception has been studied by showing participants brief examples of the actions or emotions of others presented in randomized order to prevent participants from anticipating what others do and feel. This approach is optimal to isolate the importance of information flow from lower to higher cortical areas. The degree to which feedback connections and Bayesian hierarchical predictive coding contribute to how mammals process more complex social stimuli has been less explored, and will be the focus of this review. We illustrate paradigms that start to capture how participants predict the actions and emotions of others under more ecological conditions, and discuss the brain activity measurement methods suitable to reveal the importance of feedback connections in these predictions. Together, these efforts draw a richer picture of social cognition in which predictive coding and feedback connections play significant roles. We further discuss how the notion of predicting coding is influencing how we think of autism spectrum disorder.

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9. Matthews Z, Pigden-Bennett D, Tavassoli T, Snuggs S. Comparing eating and mealtime experiences in families of children with autism, attention deficit hyperactivity disorder and dual diagnosis. Autism;2024 (Sep 12):13623613241277605.

Children with neurodevelopmental conditions like autism and attention deficit hyperactivity disorder may experience eating difficulties and related health issues later in life. Sharing family meals can help prevent these issues developing, but most studies have looked at families with neurotypical children. Our goal was to learn more about how families of children with autism, attention deficit hyperactivity disorder and both conditions (autism + attention deficit hyperactivity disorder) experience mealtimes. We developed an online survey asking caregivers about their child’s eating, mealtime experience and if they experienced stress. We tested it with nine caregivers and made improvements based on their feedback before recruiting 351 caregivers to complete the main survey. We found that families of children with neurodevelopmental conditions experienced greater food fussiness, emotional undereating, ‘problematic’ child mealtime behaviours, dietary concerns, higher stress for caregivers and spouses and less frequent conventionally structured mealtimes compared to those without these conditions. Families of children with attention deficit hyperactivity disorder and autism + attention deficit hyperactivity disorder reported greater appetite, ‘problematic’ mealtime behaviours and increased stress for caregivers and spouses compared to families of children with autism. Meanwhile, families of children with autism and autism + attention deficit hyperactivity disorder reported less enjoyment of food and less structured mealtimes compared to those with attention deficit hyperactivity disorder. Our findings highlight that families of children with neurodevelopmental conditions, particularly those with autism + attention deficit hyperactivity disorder, have different mealtime experiences and eating behaviours compared to those with neurotypical children. These families may benefit from support at mealtimes. Learning why people do or do not participate in shared family meals will be crucial to developing improved mealtime support in the future.

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10. Naguy A, Alqabandi M. Valproate-Autism Labyrinth. Psychopharmacol Bull;2024 (Aug 19);54(4):131-133.

Valproate and Autism complexity is manifold. From an established environmental risk factor for autism, to a translational animal model, valproate’s composite mode of action might unfold to address core autistic domains transcending mere aggressive behavioural control.

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11. Perez Liz G, DuBay M, Montiel-Nava C. Editorial: COVID and autism 2023: lessons learnt and future directions for research. Front Psychiatry;2024;15:1476002.

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12. Santana-Coelho D. Does the kynurenine pathway play a pathogenic role in autism spectrum disorder?. Brain Behav Immun Health;2024 (Oct);40:100839.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, sociability, and repetitive/stereotyped behavior. The etiology of autism is diverse, with genetic susceptibility playing an important role alongside environmental insults and conditions. Human and preclinical studies have shown that ASD is commonly accompanied by inflammation, and inhibition of the inflammatory response can ameliorate, or prevent the phenotype in preclinical studies. The kynurenine pathway, responsible for tryptophan metabolism, is upregulated by inflammation. Hence, this metabolic route has drawn the attention of investigators across different disciplines such as cancer, immunology, and neuroscience. Over the past decade, studies have identified evidence that the kynurenine pathway is also altered in autism spectrum disorders. In this mini review, we will explore the current status quo of the link between the kynurenine pathway and ASD, shedding light on the compelling but still preliminary evidence of this relationship.

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13. Selim B, Satti A, Abdelgadir IS. COVID-19 autism spectrum disorder-like transient neurocognitive clinical presentation. BMJ Case Rep;2024 (Sep 12);17(9)

The COVID-19 pandemic has impacted the general population in different ways, including the vulnerable population of children with special needs.In this case report, we will discuss the emergence of a transient, full-blown picture of autism spectrum disorder (ASD) in a child who contracted a COVID-19 infection, and his gradual improvement over the course of a few months. This broadens our perspective on the possible neurocognitive clinical presentations of COVID-19 infection.

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14. Soleimanpour S, Abavisani M, Khoshrou A, Sahebkar A. Probiotics for autism spectrum disorder: An updated systematic review and meta-analysis of effects on symptoms. J Psychiatr Res;2024 (Sep 11);179:92-104.

BACKGROUND: Recent researches highlighted the significant role of the gut-brain axis and gut microbiota in autism spectrum disorder (ASD), a neurobehavioral developmental disorder characterized by a variety of neuropsychiatric and gastrointestinal symptoms, suggesting that alterations in the gut microbiota may correlate with the severity of ASD symptoms. Therefore, this study was designed to conduct a comprehensive systematic review and meta-analysis of the effectiveness of probiotic interventions in ameliorating behavioral symptoms in individuals with ASD. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A comprehensive literature search was performed across multiple databases including the Cochrane Library, PubMed, Web of Science, and Google Scholar up until June 2024. Inclusion criteria encompassed published randomized clinical trials (RCTs), focusing on probiotic interventions and evaluating outcomes related to ASD behavior symptoms. The study utilized Cochrane’s Risk of Bias 2 for bias assessment and applied random effect models with inverse variance method for statistical analysis, also addressing publication bias and conducting subgroup analyses through Begg’s and Egger’s tests to explore the effects of various factors on the outcomes. RESULTS: Our meta-analysis, which looked at eight studies with a total of 318 samples from ASD patients aged 1.5-20 years, showed that the probiotic intervention group had significantly better behavioral symptoms compared to the control group. This was shown by a pooled standardized mean difference (SMD) of -0.38 (95% CI: 0.58 to -0.18, p < 0.01). Subgroup analyses revealed significant findings across a variety of factors: studies conducted in the European region showed a notable improvement with an SMD of -0.44 (95%CI: 0.72 to -0.15); interventions lasting longer than three months exhibited a significant improvement with an SMD of -0.43 (95%CI: 0.65 to -0.21); and studies focusing on both participants under and greater than 10 years found significant benefits with an SMDs of -0.37 and -0.40, respectively (95%CI: 0.65 to -0.09, and 95%CI: 0.69 to -0.11, respectively). Moreover, both multi-strain probiotics and single-strain interventions showed an overall significant improvement with a SMD of -0.53 (95%CI: 0.85 to -0.22) and -0.28 (95%CI: 0.54 to -0.02), respectively. Also, the analysis confirmed the low likelihood of publication bias and the robustness of these findings. CONCLUSION: Our study highlighted the significant improvement in ASD behavioral symptoms through probiotic supplementation. The need for personalized treatment approaches and further research to confirm efficacy and safety of probiotics in ASD management is emphasized.

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15. Talbott MR, Young GS, Ozonoff S. Can combining existing behavioral tools improve identification of infants at elevated likelihood of autism in the first year of life?. Autism;2024 (Sep 12):13623613241275455.

Many families have concerns about their infants’ development in the first year of life. Current screeners cannot tell whether these differences might be related to autism, developmental delays, or likely to resolve on their own. As a result, many families are told to « wait and see. » In this study, we looked at whether combining multiple behavior measures can improve prediction of outcomes in toddlerhood. This could help to provide families with more information about the significance of early behavioral differences. We assessed 256 infants with an older autistic sibling at 6, 9, and 12 months. We created three markers of behavioral differences at these ages. We looked at whether infants who had two or more markers were more likely to be on the autism spectrum or have other developmental differences than to have typically developing outcomes at 36 months. We found that very few infants had more than one marker at any age. However, infants who showed two or more markers were more likely to be on the spectrum or have other developmental differences at 36 months than infants who showed only one marker. These findings suggest that when behavioral differences are present on multiple measures, there is no need to wait and see before referring for services.

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16. Vacas J, Antolí A, Sánchez-Raya A, Pérez-Dueñas C, Cuadrado F. Eye-Tracking Methodology to Detect Differences in Attention to Faces Between Developmental Language Disorder and Autism. J Speech Lang Hear Res;2024 (Sep 12);67(9):3148-3162.

PURPOSE: Developmental language disorder (DLD) and autism sometimes appear as overlapping conditions in behavioral tests. There is much literature on the visual scanning pattern (VSP) of faces in autistic children, but this is scarce regarding those with DLD. The purpose of this study was to compare the VSP of faces in young children with DLD, those with autism, and typically developing peers, assessing the effect of three variables. METHOD: Two eye-tracking experiments were designed to assess the effect of the emotion and the poser’s gender (Experiment 1) and the poser’s age (Experiment 2) on the VSP of participants (Experiment 1: N = 59, age range: 32-74 months; Experiment 2: N = 58, age range: 32-74 months). We operationalized the VSP in terms of attentional orientation, visual preference, and depth of processing of each sort of face. We developed two paired preference tasks in which pairs of images of faces showing different emotions were displayed simultaneously to compete for children’s attention. RESULTS: Data analysis revealed two VSP markers common to both disorders: (a) superficial processing of faces and (b) late orientation to angry and child faces. Moreover, one specific marker for each condition was also found: typical preference for child faces in children with DLD versus diminished preference for them in autistic children. CONCLUSIONS: Considering the similarities found between children with DLD and those with autism, difficulties of children with DLD in attention to faces have been systematically underestimated. Thus, more effort must be made to identify and respond to the needs of this population. Clinical practice may benefit from the potential of eye-tracking methodology and the analysis of the VSP to assess attention to faces in both conditions. This would also contribute to the improvement of early differential diagnosis in the long run.

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17. Wahl L, Karim A, Hassett AR, van der Doe M, Dijkhuizen S, Badura A. Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models. Biol Psychiatry Glob Open Sci;2024 (Nov);4(6):100366.

BACKGROUND: Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a « behavioral fingerprint » that takes environmental and sex influences under consideration. METHODS: To this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays-the Live Mouse Tracker and Motion Sequencing-on male and female Shank2, Tsc1, and Purkinje cell-specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. RESULTS: Multiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. CONCLUSIONS: Together, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models. Traditional methods of studying behavior in mouse models of human disorders often focus on single behavioral features. The current study sought to address this gap by examining 3 autism mouse models, using a variety of traditional and novel behavioral tests and computational dimensionality reduction analyses, to create a “behavioral fingerprint” for each animal. This study also considered the effects of the environmental factor of housing conditions and sex on behavior in these models. The findings suggest that complex, multiparametric assays offer a more nuanced portrayal of behavioral variability in autism mouse models, showcasing the complex interplay of genetics, environment, and behavior. eng

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18. Weber CF, Kebets V, Benkarim O, Lariviere S, Wang Y, Ngo A, Jiang H, Chai X, Park BY, Milham MP, Di Martino A, Valk S, Hong SJ, Bernhardt BC. Contracted functional connectivity profiles in autism. Mol Autism;2024 (Sep 11);15(1):38.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean ± SD age = 20.8 ± 8.1 years) and 108 neurotypical controls (NT, 19.2 ± 7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity.

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19. Whelan S, Caulfield N, O’Doherty S, Mannion A, Leader G. Parental experiences of raising an autistic child in Ireland: A qualitative thematic analysis. Autism;2024 (Sep 12):13623613241277040.

Parenting an autistic child can be a challenging experience. Parents of autistic children often require social and professional support to cope with the various stresses they encounter and to ensure their children achieve their optimal potential. Recently, the way professional supports are organised in Ireland has changed. Very little previous recent research has investigated parents’ experiences of raising an autistic child in Ireland. This study interviewed six parents asking them about their challenges, stress levels, coping strategies and their perceptions regarding professional support services. The data from these interviews were organised into themes. A major finding was that parents felt the healthcare system was failing to provide help for their children, and that support services in Ireland can cause more parental distress than dealing with their child’s difficulties. Other causes of parental stress included the child’s behaviours that they found challenging, stigma, a lack of awareness about autism and isolation. This study shows that both autistic children and their parents are at increased risk of developing mental health problems due to a flawed healthcare system that requires improvement urgently.

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20. Yao M, Daniels J, Grosvenor L, Morrill V, Feinberg JI, Bakulski KM, Piven J, Hazlett HC, Shen MD, Newschaffer C, Lyall K, Schmidt RJ, Hertz-Picciotto I, Croen LA, Fallin MD, Ladd-Acosta C, Volk H, Benke K. Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder. J Neurodev Disord;2024 (Sep 12);16(1):54.

BACKGROUND: Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. METHODS: We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. RESULTS: Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. LIMITATIONS: The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. CONCLUSIONS: We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits.

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