1. Agarwal N, Frigerio G, Rizzato G, Ciceri T, Mani E, Lanteri F, Molteni M, Carare RO, Losa L, Peruzzo D. Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder. Commun Med (Lond);2024 (Oct 4);4(1):191.

BACKGROUND: The parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics. METHODS: In this retrospective study, we investigated potential correlations between parasagittal dura volume, brain structure volumes, and clinical severity scales in young children with autism spectrum disorder. We employed a semi-supervised two step pipeline to extract parasagittal dura volume from 3D-T2 Fluid Attenuated Inversion Recovery sequences, based on U-Net followed by manual refinement of the extracted parasagittal dura masks. RESULTS: Here we show that the parasagittal dura volume does not change with age but is significantly correlated with cerebrospinal fluid (p-value = 0.002), extra-axial cerebrospinal fluid volume (p-value = 0.0003) and severity of developmental delay (p-value = 0.024). CONCLUSIONS: These findings suggest that autism spectrum disorder children with severe developmental delay may have a maldeveloped parasagittal dura that potentially perturbs cerebrospinal fluid dynamics. Cerebrospinal fluid (CSF) is produced in the brain. It is a medium of transport for neural growth factors and waste products. CSF is drained out of the brain through multiple pathways, one of them being the recently identified parasagittal dura (PSD) which also plays a role in the immune system within the brain. We estimated the PSD volume in children with autism spectrum disorder (ASD) and found the volume was associated with the amount of CSF in the brain. We also found that the PSD volume is smaller in children who have severe forms of developmental delay. Our findings suggest problems in the development of the PSD could have in impact on brain development and waste removal in children with ASD. More research in this area could enable a better understanding of the underlying causes of ASD. eng

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2. Alshawsh M, Wake M, Gecz J, Corbett M, Saffery R, Pitt J, Greaves R, Williams K, Field M, Cheong J, Bui M, Arora S, Sadedin S, Lunke S, Wall M, Amor DJ, Godler DE. Epigenomic newborn screening for conditions with intellectual disability and autistic features in Australian newborns. Epigenomics;2024 (Oct 4):1-12.

This study describes a protocol to assess a novel workflow called Epi-Genomic Newborn Screening (EpiGNs) on 100,000 infants from the state of Victoria, Australia. The workflow uses a first-tier screening approach called methylation-specific quantitative melt analysis (MS-QMA), followed by second and third tier testing including targeted methylation and copy number variation analyzes with droplet digital PCR, EpiTYPER system and low-coverage whole genome sequencing. EpiGNs utilizes only two 3.2 mm newborn blood spot punches to screen for genetic conditions, including fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Dup15q syndrome and sex chromosome aneuploidies. The program aims to: identify clinically actionable methylation screening thresholds for the first-tier screen and estimate prevalence for the conditions screened. [Box: see text]. eng

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3. Asta L, Ricciardello A, Cucinotta F, Turriziani L, Boncoddo M, Bellomo F, Angelini J, Gnazzo M, Scandolo G, Pisanò G, Pelagatti F, Chehbani F, Camia M, Persico AM. Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome. J Neurodev Disord;2024 (Oct 3);16(1):57.

BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). OBJECTIVES: To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. METHODS: 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. RESULTS: Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001). CONCLUSIONS: We replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way.

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4. Chan AS, Leung PY, Pang TW, Sze SL. Eye-tracking training improves visuospatial working memory of children with attention-deficit/hyperactivity disorder and autism spectrum disorder. Autism Res;2024 (Oct 4)

Given the close connection between eye movement and frontal lobe functions and some evidence supporting the effect of eye-tracking training on enhancing cognitive performance mediated by the frontal lobe, this study aimed to explore if after-school eye-tracking training can improve the visuospatial working memory (VSWM) and cognitive flexibility performance in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). This study is a non-randomized cluster trial. Forty children from eight primary schools were selected, half receiving eye-tracking training for 20 sessions over 9 months, while the other half served as a waitlist control. They were matched on demographic characteristics and baseline cognitive performance. Their VSWM and cognitive flexibility were assessed at the beginning and end of the study. Results showed that children who received eye-tracking training, but not those on a waitlist, exhibited significant improvements in the total score and working memory span of the VSWM tests, and the correct responses in cognitive flexibility tests. Specifically, VSWM performance at higher span levels (5 or above) yielded a greater improvement. The findings suggest that eye-tracking training can be a feasible and effective after-school program for improving working memory and cognitive flexibility performance in children with ADHD and ASD. This study was prospectively registered at ClinicalTrials.gov (https://clinicaltrials.gov/, trial number: NCT05428657).

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5. Dellapiazza F, Rattaz C, Michelon C, Peyre H, Picot MC, Baghdadli A. Longitudinal change in symptom severity in children with ASD: Results from the ELENA cohort. Autism Res;2024 (Oct 4)

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition and understanding the changes in autism symptoms over time is crucial for tailoring support and interventions. This study therefore aimed to investigate the changes in symptom severity in a large cohort of children with ASD over a three-year follow-up period and identify factors that influence these changes. The study included 575 children diagnosed with ASD, ranging in age from 2 to 12 years, who were assessed at baseline and again 3 years later using the Autism Diagnostic Observational Schedule-2 (ADOS-2). ASD severity changes were investigated using the ADOS calibrated severity score (CSS) scores for total, social affect (SA) and restricted and repetitive behaviors (RRB). Results highlight four distinct patterns: stable high, stable low, increased, and decreased severity. The ADOS CSS total score changed for half of the sample, reflecting an increase in ASD severity for 21.9% and a decrease for 29.1% of children. For the other half, the ADOS CSS score remained stable, either high (34.4%) or low (14.6%). While the majority of previous studies reported stability in ASD severity, our findings revealed significant variability with frequent improvements in SA symptoms whereas RRBs remained stable or worsened. Our findings also showed that an improvement in SA was associated with the youngest group and early diagnosis. However, no clinical or sociodemographic factors were linked to changes in RRB, emphasizing the necessity for RRB-specific therapies. The third six-year follow-up point of the ongoing ELENA cohort study will map the long-term trajectories of the severity of ASD symptoms and their potential risk factors.

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6. Edgar TC, Schlosser RW, Koul R. Socio-Communicative Behaviors Involving Minimally Speaking Autistic Preschoolers and Their Typically Developing Peers: Effects of an Augmentative and Alternative Communication Intervention Package. J Speech Lang Hear Res;2024 (Oct 4):1-21.

PURPOSE: The purpose of this study was to examine the effectiveness of an augmentative and alternative communication (AAC) intervention package consisting of systematic instruction and aided AAC modeling with speech-output technology on the acquisition, maintenance, and generalization of socio-communicative behaviors in four minimally speaking, preschool-aged, autistic children. METHOD: A multiple-probe design across behaviors (i.e., initiating a request for a turn, answering questions, and commenting) replicated across participants was implemented to evaluate the effects of the intervention package on socio-communicative behaviors. Furthermore, a pretreatment and posttreatment multiple-generalization-probe design was used to assess generalization across typically developing peers who were not a part of the intervention. Maintenance data were collected 3 weeks post intervention. RESULTS: Visual analysis, corroborated by nonoverlapping of all pairs statistics, established a strong functional relationship between the AAC intervention package and all targeted socio-communicative outcomes for two participants. For the other two participants, inconsistent intervention effects were observed. In terms of generalization from interacting with the researcher to typically developing peers, a functional relationship between the intervention and generalization outcomes for all targeted behaviors was established for only one participant (i.e., Aiden). CONCLUSION: The outcomes of this study suggest that aided AAC modeling and systematic instruction using a speech-output technology may lead to gains in socio-communicative behaviors in some minimally speaking, preschool-aged, autistic children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27091879.

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7. Elliott JK, Buchanan K, Bayes S. The neurodivergent perinatal experience – A systematic literature review on autism and attention deficit hyperactivity disorder. Women Birth;2024 (Oct 2);37(6):101825.

BACKGROUND: Neurodivergent individuals often face unique challenges during the perinatal period, which can significantly impact their experiences of pregnancy, childbirth, and early parenting. Despite growing awareness of neurodiversity, there remains a gap in perinatal care that fully addresses the lived experiences and needs of those with neurodivergent conditions such as Autism (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). OBJECTIVE: To compile and analyse recent literature on the perinatal experiences of neurodivergent parturients. To provide an overview of current knowledge, identify prevalent challenges, and suggest opportunities for improving perinatal services. Additionally, we aim to highlight research gaps that guide future studies and enhance care quality for neurodivergent individuals during the perinatal period. METHODS: The Systematic Reviews methodological process was utilised to search relevant scientific databases to gather current research articles on neurodivergent perinatal experiences. Eleven studies met the inclusion criteria and were appraised using a rigorous quality checklist. Thematic analysis identified recurring themes across the selected papers. RESULTS: Three major themes emerged: Care provider support, Perinatal mental health needs, and Resilience and growth of neurodivergent parturients. These themes highlight significant differences in perinatal experiences between neurodivergent and neurotypical individuals, underscoring the need for tailored care approaches. CONCLUSION: The findings reveal that current perinatal care practices do not adequately address the specific challenges faced by perinatal neurodivergent individuals. There is a critical need for perinatal care systems to integrate neurodiversity-affirming practices. Future research should consider intersectionality to include marginalised and underrepresented neurodivergent voices.

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8. Ethridge LE, Pedapati EV, Schmitt LM, Norris JE, Auger E, De Stefano LA, Sweeney JA, Erickson CA. Validating brain activity measures as reliable indicators of individual diagnostic group and genetically mediated sub-group membership Fragile X Syndrome. Sci Rep;2024 (Oct 3);14(1):22982.

Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing attention on biological pathways and associated measures, such as electroencephalography (EEG), with strong translational potential and small molecule target engagement. This study utilized guided machine learning to test promising translational EEG measures (resting power and auditory chirp oscillatory variables) in a large heterogeneous sample of individuals with FXS to identify best performing EEG variables for reliably separating individuals with FXS, and genetically-mediated subgroups within FXS, from typically developing controls. Best performing variables included resting relative frontal theta power, all combined posterior-head resting power bands, posterior peak alpha frequency (PAF), combined PAF across all measured regions, combined theta, alpha, and gamma power during the chirp, and all combined chirp oscillatory variables. Sub-group analyses for resting EEG best discriminated non-mosaic FXS males via frontal theta resting relative power (AUC = 0.8759), even with data reduced to a 20-channel clinical montage (AUC = 0.9062). In the chirp task, FXS females and non-mosaic males were nearly perfectly discriminated by combined theta, alpha, and gamma power (AUC = 0.9444) and a combination of all variables (AUC = 0.9610), respectively. Results support use of resting and auditory oscillatory tasks to reliably identify neural deficit in FXS, and to identify specific translational targets for genetically-mediated sub-groups, supporting potential points for stratification.

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9. Gora C, Dudas A, Vaugrente O, Drobecq L, Pecnard E, Lefort G, Pellissier LP. Deciphering autism heterogeneity: a molecular stratification approach in four mouse models. Transl Psychiatry;2024 (Oct 4);14(1):416.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication, as well as restrained or stereotyped behaviors. The inherent heterogeneity within the autism spectrum poses challenges for developing effective pharmacological treatments targeting core features. Successful clinical trials require the identification of robust markers to enable patient stratification. In this study, we identified molecular markers within the oxytocin and immediate early gene families across five interconnected brain structures of the social circuit. We used wild-type and four heterogeneous mouse models, each exhibiting unique autism-like behaviors modeling the autism spectrum. While dysregulations in the oxytocin family were model-specific, immediate early genes displayed widespread alterations, reflecting global changes across the four models. Through integrative analysis, we identified Egr1, Foxp1, Homer1a, Oxt, and Oxtr as five robust and discriminant molecular markers that allowed the successful stratification of the four models. Importantly, our stratification demonstrated predictive values when challenged with a fifth mouse model or identifying subgroups of mice potentially responsive to oxytocin treatment. Beyond providing insights into oxytocin and immediate early gene mRNA dynamics, this proof-of-concept study represents a significant step toward the potential stratification of individuals with ASD. This work has implications for the success of clinical trials and the development of personalized medicine in autism.

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10. Henbest VS, Apel K. The Relation of Linguistic Awareness Skills to Reading and Spelling for Autistic and Non-Autistic Elementary School-Age Children. J Speech Lang Hear Res;2024 (Oct 8);67(10):3691-3713.

PURPOSE: For non-autistic children, it is well established that linguistic awareness skills support their success with reading and spelling. Few investigations have examined whether these same linguistic awareness skills play a role in literacy development for autistic elementary school-age children. This study serves as a first step in quantifying the phonological, prosodic, orthographic, and morphological awareness skills of autistic children; how these skills compare to those of non-autistic children; and their relation to literacy performance. METHOD: We measured and compared the phonological, prosodic, orthographic, and morphological awareness skills of 18 autistic (with average nonverbal IQs) and 18 non-autistic elementary school-age children, matched in age, nonverbal IQ, and real-word reading. The relations between linguistic awareness and the children’s word-level literacy and reading comprehension skills were examined, and we explored whether the magnitude of these relations was different for the two groups. Regression analyses indicated the relative contribution of linguistic awareness variables to performance on the literacy measures for the autistic children. RESULTS: The non-autistic children outperformed the autistic children on most linguistic awareness measures. There were moderate-to-strong relations between performances on the linguistic awareness and literacy measures for the non-autistic children, and most associations were not reliably different from those for the autistic children. Regression analyses indicate that the performance on specific linguistic awareness variables explains unique variance in autistic children’s literacy performance. CONCLUSION: Although less developed than those of their non-autistic peers, the linguistic awareness skills of autistic elementary school-age children are important for successful reading and spelling.

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11. Kilili-Lesta M, Giannakou K, Voniati L. Early development score as a prognostic factor in nonverbal/minimally verbal children with autism spectrum disorder: A matched case-control study in Cyprus. Autism Dev Lang Impair;2024 (Jan-Dec);9:23969415241286403.

BACKGROUND AND AIMS: Children with autism spectrum disorder (ASD) present with impairments in social interaction and stereotypic behaviors. About a third may exhibit delays in verbal expression beyond preschool age, potentially categorizing them as nonverbal/minimally verbal (NV/MV), a condition that can persist into adulthood and affect their quality of life. The risk and prognostic factors associated with this reduced verbal outcome remain uncertain. This study aims to identify such factors within children diagnosed with ASD in Cyprus. METHODS: In this case-control study, 56 children aged 3-12 years, with an ASD diagnosis, participated. Among them, cases were 22 children classified as ASD-NV/MV, and controls were 34 children classified as verbal (ASD-V), matched by age group and gender. Retrospective information on familial, perinatal, and developmental risk and prognostic factors were collected to calculate the familial risk score (FRS), perinatal risk score (PRS), and developmental risk score (DRS). Early development information was collected for the Early Development Score (EDS) and Early Gesture Score (EGS), to measure the children’s skill level as toddlers across milestones. A low EDS and/or low EGS reflected general developmental delays and decreased frequency of early gestures and were considered in the DRS. A parent report questionnaire was utilized to determine the current overall linguistic level and status of participants, distinguishing cases from controls. RESULTS: Age group and gender-matched cases and controls were similar in socioeconomic status and demographic characteristics (p > .05). Among the various familial (e.g., sibling with ASD), perinatal (e.g., prematurity), and developmental (e.g., ASD regression) factors examined individually, as well as collectively as scores in a conditional logistic regression (CLR) model, only a high DRS (p = .03), due to low EDS (p = .04) was significantly associated with linguistic status. When considering all risk scores in a multivariate CLR model, children with a high DRS were more likely to belong to the cases than to the control group (p = .02). In a subsequent model with low EDS and low EGS, only the low EDS was significantly associated with the case group. Results showed that children with ASD and a low EDS, reflecting general delays in early development, were 4.5 times more likely to belong to the cases group than those with a high EDS (p = .02). CONCLUSIONS: Early developmental delays in developmental milestones across various domains like gesture, motor, play, linguistic, cognition, and joint attention, in toddlerhood, were associated with later decreased verbal outcomes. Children in the sample with such early delays (low EDS), had a higher likelihood of persistent language delays (ASD-NV/MV) even at late school age. Future studies are needed to duplicate findings and explore possible contributing factors affecting linguistic outcome in ASD through prospective studies exploring within ASD differences. IMPLICATIONS: These findings emphasized the importance of monitoring early development closely for children at risk for ASD, pre-diagnosis, to provide additional early support for those more likely to be ASD-NV/MV. Parents and specialists like pediatricians, educators, speech-language pathologists, among others, can track the EDS score of children at risk for ASD and refer to the appropriate specialists for early stimulation, intervention, and parent consultation promptly.

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12. Kuo YC, Ni HC, Liu CH. The associations between self-rated autistic traits, social camouflaging, and mental health outcomes in Taiwanese anime, comics and games (ACG) doujin creators: an exploratory study. BMC Psychol;2024 (Oct 3);12(1):531.

BACKGROUND: Doujin (どうじん) is a Japanese term referring to a circle where people share the same interests, usually something that belongs to the Anime, Comics, and Games (ACG) subculture. Individuals who belong to it and create related works, known as ACG doujin creators, are usually described as socially awkward and at potential risk of isolation. In such a context, they may theoretically exhibit higher autistic traits and manifest camouflaging tendencies, which may consequently be associated with their mental health. Nonetheless, the impact of autistic traits and camouflaging on mental health in this subculture remains significantly underexplored. METHODS: We recruited 183 Taiwanese ACG doujin creators (age ranges from 18 to 41, 146 female and 37 male) via social networking platforms. Participants completed Chinese online surveys assessing socio-demographic information, doujin activities, past psychiatric history, the 35-item Version of Autism-Spectrum Quotient (AQ-35), Chinese version Camouflaging Autistic Traits Questionnaire (CAT-Q-Ch), the General Anxiety Disorder-7 (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). Linear regression analysis was employed to examine the associations between the aforementioned scales. RESULTS: Our findings revealed that among ACG doujin creators, descriptively higher level of AQ-35 and CAT-Q-Ch than previous studies were found. Moreover, we observed a positive association between camouflaging behaviours and most AQ-35 subscales, with the exception of the mindreading subscale. Additionally, we identified that both camouflaging and autistic traits were significantly linked to higher PHQ-9 and GAD-7 scores. CONCLUSIONS: Through this study, we gained insight into the distinctive characteristics of autistic traits, camouflaging behaviours, and mental health among Taiwanese ACG doujin creators, as the associations between the factors mentioned above are divergent compared to previous research. This topic demonstrated that camouflaging is also associated with adverse mental health in a subculture group.

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13. Li F, Cheng T, Yan M, Li T, Zhang T, Huang Y, Tang J. Analysis of the therapeutic effect of right mid-axillary approach in the surgical treatment of ASD and VSD in children. J Cardiothorac Surg;2024 (Oct 3);19(1):587.

BACKGROUND: To compare the therapeutic effects of right vertical infra-axillary thoracotomy (RVIAT) and Standard Median Sternotomy (SMS) in the repair of atrial septal defect (ASD) and ventricular septal defect (VSD), and to evaluate the safety and effectiveness of right subaxillary incision technique in the surgical treatment of common congenital heart disease (CHD) in children. METHODS: Data of children diagnosed with ASD repair or VSD repair at our center from September 2019 to September 2022 were collected. Based on propensity score matching, 214 children (107 in the RVIAT group and 107 in the SMS group) who completed ASD repair surgery and 242 children (121 in the RVIAT group and 121 in the SMS group) who completed VSD repair surgery were selected for the study. The perioperative and follow-up data of the two surgical approaches were compared to evaluate clinical efficacy. RESULTS: There was no statistically significant difference (p > 0.05) between the two surgical approaches in terms of surgical time, aortic occlusion time, total amount of ultrafiltration fluid, ICU stay time, and hospital stay; The intraoperative blood loss and total postoperative drainage fluid in the RVIAT group were lower than those in the SMS group (p < 0.05); The incidence of postoperative thoracic deformities in the SMS group is higher than that in the RVIAT group. CONCLUSION: The safety and effectiveness of the two approaches are similar, but RVIAT has less intraoperative bleeding, less postoperative drainage fluid and tube time, and better concealment and cosmetic effects, which is worthy of further clinical promotion and application.

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14. Matuskey D, Yang Y, Naganawa M, Koohsari S, Toyonaga T, Gravel P, Pittman B, Torres K, Pisani L, Finn C, Cramer-Benjamin S, Herman N, Rosenthal LH, Franke CJ, Walicki BM, Esterlis I, Skosnik P, Radhakrishnan R, Wolf JM, Nabulsi N, Ropchan J, Huang Y, Carson RE, Naples AJ, McPartland JC. (11)C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults. Mol Psychiatry;2024 (Oct 4)

The neural bases of autism are poorly understood at the molecular level, but evidence from animal models, genetics, post-mortem studies, and single-gene disorders implicate synaptopathology. Here, we use positron emission tomography (PET) to assess the density of synapses with synaptic vesicle glycoprotein 2A (SV2A) in autistic adults using (11)C-UCB-J. Twelve autistic (mean (SD) age 25 (4) years; six males), and twenty demographically matched non-autistic individuals (26 (3) years; eleven males) participated in a (11)C-UCB-J PET scan. Binding potential, BP(ND), was the primary outcome measure and computed with the centrum semiovale as the reference region. Partial volume correction with Iterative Yang was applied to control for possible volumetric differences. Mixed-model statistics were calculated for between-group differences. Relationships to clinical characteristics were evaluated based on clinician ratings of autistic features. Whole cortex synaptic density was 17% lower in the autism group (p = 0.01). All brain regions in autism had lower (11)C-UCB-J BP(ND) compared to non-autistic participants. This effect was evident in all brain regions implicated in autism. Significant differences were observed across multiple individual regions, including the prefrontal cortex (-15%, p = 0.02), with differences most pronounced in gray matter (p < 0.0001). Synaptic density was significantly associated with clinical measures across the whole cortex (r = 0.67, p = 0.02) and multiple regions (rs = -0.58 to -0.82, ps = 0.05 to <0.01). The first in vivo investigation of synaptic density in autism with PET reveals pervasive and large-scale lower density in the cortex and across multiple brain areas. Synaptic density also correlated with clinical features, such that a greater number of autistic features were associated with lower synaptic density. These results indicate that brain-wide synaptic density may represent an as-yet-undiscovered molecular basis for the clinical phenotype of autism and associated pervasive alterations across a diversity of neural processes.

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15. Natraj S, Kojovic N, Maillart T, Schaer M. Video-audio neural network ensemble for comprehensive screening of autism spectrum disorder in young children. PLoS One;2024;19(10):e0308388.

A timely diagnosis of autism is paramount to allow early therapeutic intervention in preschoolers. Deep Learning tools have been increasingly used to identify specific autistic symptoms. But they also offer opportunities for broad automated detection of autism at an early age. Here, we leverage a multi-modal approach by combining two neural networks trained on video and audio features of semi-standardized social interactions in a sample of 160 children aged 1 to 5 years old. Our ensemble model performs with an accuracy of 82.5% (F1 score: 0.816, Precision: 0.775, Recall: 0.861) for screening Autism Spectrum Disorders (ASD). Additional combinations of our model were developed to achieve higher specificity (92.5%, i.e., few false negatives) or sensitivity (90%, i.e. few false positives). Finally, we found a relationship between the neural network modalities and specific audio versus video ASD characteristics, bringing evidence that our neural network implementation was effective in taking into account different features that are currently standardized under the gold standard ASD assessment.

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16. Qing P, Zhang X, Liu Q, Huang L, Xu D, Le J, Kendrick KM, Lai H, Zhao W. Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder. Mol Autism;2024 (Oct 4);15(1):43.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. METHODS: In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). RESULTS: In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. CONCLUSION: This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD.

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17. Schmitt LM, Nelson M, Shaffer RC, Erickson CA. A near normal distribution of IQ in Fragile X Syndrome. Sci Rep;2024 (Oct 4);14(1):23058.

Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of FMR1-protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning. A sample of 143 individuals with FXS (69% male), aged 8-50 years, completed IQ testing and blood draw via venipuncture to determine the relationship between Deviation IQ scores and FMRP levels as well as the distribution of Deviation IQ scores. In both males and females with FXS, higher FMRP levels were associated with higher Deviation IQ. However, this relationship was no longer significant when only examining full mutation, fully-methylated males. Yet, both the full and restricted male samples showed a downward shifted but otherwise normal distribution of Deviation IQ scores. Our findings support and extend previous studies establishing molecular markers of disease severity in FXS as well as provide novel evidence of a « FXS IQ standard curve ». This latter finding suggests inter-individual variation in Deviation IQ in FXS, especially among males, may be driven by similar factors known to impact cognitive outcomes in typically-developing individuals. Thus, future work aimed at understanding the mechanisms by which FMRP loss leads to intellectual disability should revisit the biological/genetic, socio-environmental, and epigenetic factors contributing to inter-individual variation in IQ in FXS.

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18. Schonath M, Arnold L, Haas NA, Fischer M. Psychosocial burden and quality of life of parents with children with univentricular hearts compared to ASD parents and parents of heart-healthy children. Cardiol Young;2024 (Oct 4):1-8.

BACKGROUND: Patients with univentricular hearts can only be palliated by a staged surgical procedure that carries a high morbidity and mortality risk. The aim of this study was to examine the emotional demands, psychosocial burden, and quality of life of parents with children with univentricular hearts compared to parents of children with a simple heart defect, those with no heart defect and children with chronic diseases. METHODS: An anonymous questionnaire was created to interview parents about their quality of life, stressors, needs, strategies for coping with illness, and partnership satisfaction. RESULTS: 73 families participated in the study. Parents of children with univentricular hearts experience a significantly higher psychosocial burden, limitations in daily life, and distress in family interactions, as well as greater emotional distress compared to the other study groups. When comparing the families of children with other chronic diseases (e.g. cystic fibrosis, chronic arthritis and diabetes), these differences remained significant. CONCLUSION: The study confirms a higher psychosocial burden, restrictions in daily life and a lower quality of life of parents with children with univentricular hearts, compared to parents of children with simple heart defects and parents of heart-healthy children or those with other chronic diseases. Since this condition persists until adolescence and adulthood, the families are exposed to special challenges and stresses throughout their lives. This has yet to be adequately addressed in the management of these families.

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19. Sörnyei D, Vass Á, Németh D, Farkas K. Autistic and schizotypal traits exhibit similarities in their impact on mentalization and adult attachment impairments: a cross-sectional study. BMC Psychiatry;2024 (Oct 3);24(1):654.

BACKGROUND: Deficits in mentalizing and attachment occur in the autism and schizophrenia spectrum, and their extended traits in the general population. Parental attachment and the broader social environment highly influence the development of mentalizing. Given the similarities in the symptomatology and neurodevelopmental correlates of autism spectrum disorder (ASD) and schizophrenia (SCH), it is crucial to identify their overlaps and differences to support screening, differential diagnosis, and intervention. METHODS: This cross-sectional study utilized questionnaire data from 2203 adults (65.1% female, mean age[SD] = 37.98[9.66]), including participants diagnosed with ASD, SCH, and those exhibiting subclinical traits to investigate the associations between mentalizing, attachment, and perceived social support during adolescence across the autistic and schizotypy spectrum. RESULTS: It was revealed that both autistic and schizotypal traits have comparable effects on insecure adult attachment, primarily through challenges in mentalizing. The impact of mentalizing deficits on adult attachment slightly varies between autistic and schizotypal traits. Conversely, perceived social support during adolescence relates to improved mentalizing and secure adult attachment as a protective factor during development. CONCLUSIONS: These outcomes highlight the significance of supportive therapeutic relationships and community care while suggesting directions for further research and collaborative treatments addressing ASD and SCH, considering the differential impact of mentalizing on adult attachment.

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20. Sumbane GO. Coping strategies adopted by caregivers of children with autism in the Limpopo Province, South Africa. Afr J Disabil;2024;13:1384.

BACKGROUND: Emotion- and problem-focused coping strategies are frequently employed by caregivers of autistic children to increase their general well-being and resilience to the stress of raising the child. Although these strategies cannot directly address the situation, it is useful for handling stressful situations that cannot change. OBJECTIVES: The study seeks to explore and understand the emotion- and problem-focused strategies that caregivers use to cope with the challenges of raising a child with autism. METHOD: This was a qualitative, exploratory and descriptive research study. Twenty-eight caregivers were purposive-convenient sampled from the public special schools where their autism spectrum disorder (ASD) children are schooling. Semi-structured interviews were used to gather data, which were then transcribed and subjected to thematic analysis. RESULTS: Positive emotion-focused strategies include positive reappraisal, reframing and acceptance. Negative emotion-focused strategies include denial, emotional release, cognitive distortion, self-isolation, overprotection, negative self-talk, punishment and religion. Problem-focused coping strategies include active and adaptive coping, peer group, professional support and social support. CONCLUSION: The coping methods that have been identified can be integrated into intervention programmes and serve as a guide for specialised institutions that offer more extensive knowledge and assistance to families who are caring for children with ASD. CONTRIBUTION: The study contributes to understanding the emotion- and problem-focused strategies adopted by rural caregivers in managing their emotions, interpretation of the situation and adjusting to the demands of raising an autistic child.

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21. Yu X, Kleeman MJ, Lin JC, Chow T, Martinez MP, Chen Z, Chen JC, Eckel SP, Schwartz J, Lurmann FW, McConnell R, Xiang AH, Rahman MM. Decomposing the variance: The unique and shared associations of fine and ultrafine particulate matter exposed during pregnancy with child autism spectrum disorder. Sci Total Environ;2024 (Oct 2);954:176609.

While fine particulate matter (PM(2.5)) has been associated with autism spectrum disorder (ASD), few studies focused on ultrafine particles (PM(0.1)). Given that fine and ultrafine particles can be highly correlated due to shared emission sources, challenges remain to distinguish their health effects. In a retrospective cohort of 318,371 mother-child pairs (4549 ASD cases before age 5) in Southern California, pregnancy average PM(2.5) and PM(0.1) were estimated using a California-based chemical transport model and assigned to residential addresses. The correlation between PM(2.5) and PM(0.1) was 0.87. We applied a two-step variance decomposition approach: first, decomposing PM(2.5) and PM(0.1) into the shared and unique variances using ordinary least squares linear regression (OLS) and Deming regression considering errors in both exposures; then assessing associations between decomposed PM(2.5) and PM(0.1) and ASD using Cox proportional hazard models adjusted for covariates. Prenatal PM(2.5) and PM(0.1) each was associated with increased ASD risk. OLS decomposition showed that associations were driven mainly by their shared variance, not by their unique variance. Results from Deming regression considering assumptions of measurement errors were consistent with those from OLS. This decomposition approach has potential to disentangle health effects of correlated exposures, such as PM(2.5) and PM(0.1) from common emissions sources.

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22. Zane ER, Grossman RB. Normal but Different: Autistic Adolescents Who Score Within Normal Ranges on Standardized Language Tests Produce Frequent Linguistic Irregularities in Spontaneous Discourse. Autism Dev Lang Impair;2024 (Jan-Dec);9:23969415241283378.

BACKGROUND AND AIMS: A substantial minority of autistic individuals score within typical ranges on standard language tests, suggesting that autism does not necessarily affect language acquisition. This idea is reflected in current diagnostic criteria for autism, wherein language impairment is no longer included. However, some work has suggested that probing autistic speakers’ language carefully may reveal subtle differences between autistic and nonautistic people’s language that cannot be captured by standardized language testing. The current study aims to test this idea, by determining whether a group of autistic and nonautistic individuals who score similarly on a standardized test show differences in the number of unconventional and erroneous language features they produce in a spontaneous language sample. METHODS: Thirty-eight older children and adolescents (19 autistic; 19 nonautistic), between the ages of 10 and 18, were recruited. Both participant groups scored within normal ranges on standardized language and IQ tests. Participants engaged in a « double interview » with an experimenter, during which they were first asked questions by the experimenter about themselves, and then they switched roles, so that it was the participant’s turn to ask the experimenter questions. Participants’ language during the interview was transcribed and analyzed for linguistic irregularities, including both semantic anomalies and morphosyntactic errors. RESULTS: Group membership accounted for significant variance in irregularity frequency; autistic participants produced more linguistic irregularities than nonautistic participants. Scores on a standardized language test did not improve model fit. Secondary analyses involving irregularity type (semantic vs. morphosyntactic) showed that group differences were primarily driven by relatively high numbers of semantic unconventionalities produced by the autistic group. While the autistic group made more morphosyntactic errors than the nonautistic group, differences in these numbers were only marginally significant. CONCLUSIONS AND IMPLICATIONS: These findings suggest that a commonly used standardized language test does not adequately predict the number and perhaps type of language irregularities produced by some older autistic children and adolescents during spontaneous discourse. Results also suggest that differences in language use, especially semantic differences, may characterize autistic language, even the language produced by people who score within normal ranges on standardized language tests. It is debatable whether differences reflect underlying language impairments and/or a linguistic style adopted/preferred by autistic speakers. In this paper, we discuss both possibilities and offer suggestions to future research for teasing these possibilities apart.

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