1. Denisova K, Wolpert DM. Sensorimotor variability distinguishes early features of cognition in toddlers with autism. iScience;2024 (Sep 20);27(9):110685.

The potential role of early sensorimotor features to atypical human cognition in autistic children has received surprisingly little attention given that appropriate movements are a crucial element that connects us to other people. We examined quantitative and observation-based movements in over 1,000 toddlers diagnosed with autism spectrum disorder (ASD) with different levels of cognitive abilities (intelligence quotient, IQ). Relative to higher-IQ ASD toddlers, those with lower-IQ had significantly altered sensorimotor features. Remarkably, we found that higher IQ in autistic toddlers confers resilience to atypical movement, as sensorimotor features in higher-IQ ASD children were indistinguishable from those of typically developing healthy control toddlers. We suggest that the altered movement patterns may affect key autistic behaviors in those with lower intelligence by affecting sensorimotor learning mechanisms. Atypical sensorimotor functioning is a key feature in lower-IQ early childhood autism. These findings have implications for the development of individualized interventions for subtypes of autism.

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2. Ding Z, Mei S, Zhang B, Kong J, Liu L, Zhang Z, Wang C, Zhang Y. [Comprehensive diagnosis and genetic analysis of two children with ring chromosome 18]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2024 (Sep 10);41(9):1110-1116.

OBJECTIVE: To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes. METHODS: Two patients treated at the Children’s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). RESULTS: Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.21q22.1)[40]/46,XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11-21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them. CONCLUSION: Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

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3. Fang J, Zhang DF, Xie K, Xu L, Bi XA. Bilinear Perceptual Fusion Algorithm Based on Brain Functional and Structural Data for ASD Diagnosis and Regions of Interest Identification. Interdiscip Sci;2024 (Sep 10)

Autism spectrum disorder (ASD) is a serious mental disorder with a complex pathogenesis mechanism and variable presentation among individuals. Although many deep learning algorithms have been used to diagnose ASD, most of them focus on a single modality of data, resulting in limited information extraction and poor stability. In this paper, we propose a bilinear perceptual fusion (BPF) algorithm that leverages data from multiple modalities. In our algorithm, different schemes are used to extract features according to the characteristics of functional and structural data. Through bilinear operations, the associations between the functional and structural features of each region of interest (ROI) are captured. Then the associations are used to integrate the feature representation. Graph convolutional neural networks (GCNs) can effectively utilize topology and node features in brain network analysis. Therefore, we design a deep learning framework called BPF-GCN and conduct experiments on publicly available ASD dataset. The results show that the classification accuracy of BPF-GCN reached 82.35%, surpassing existing methods. This demonstrates the superiority of its classification performance, and the framework can extract ROIs related to ASD. Our work provides a valuable reference for the timely diagnosis and treatment of ASD.

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4. García-Zambrano S, Pinto-Ocampo RH. How Many Autistic Children are there in Colombia? A Nationwide Examination of Autism Through Health System Data. J Autism Dev Disord;2024 (Sep 10)

PURPOSE: Accurate healthcare data is indispensable for monitoring the epidemiology of autism spectrum disorders (ASD) and improving the quality of care for individuals on the spectrum. In Colombia, the Ministry of Health has developed the social protection information system (SISPRO) as a comprehensive registry, drawing data from the healthcare system with close to universal coverage (approximately 95%). This study utilizes data gathered by SISPRO to estimate the prevalence and specific characteristics of autistic children registered between January 2020 and December 2022. METHOD: A descriptive epidemiological approach was employed, using the International Statistical Classification of Diseases as search terms for ASD within the SISPRO dataset. RESULTS: The study revealed a prevalence of 13.788 cases per 10,000 children in 2022 among aged 4 to 14. Regarding healthcare coverage types in 2022, the majority of autistic children served were under the contributory regime (68.28%), followed by the subsidized regime (25.36%). Geographic analysis indicated a non-uniform distribution of ASD prevalence in Colombia. The regions with the highest GDP, such as Antioquia, Atlántico, Bogotá, Cundinamarca, and Valle del Cauca, exhibited the highest prevalence (M = 17.90; SD = 14.3). In contrast, areas with the lowest GDP, including Amazonas, Guainía, Vaupés, Vichada, and Guaviare, showed the lowest prevalence among children (M = 2.6; SD = 2.5). CONCLUSION: The estimation of ASD prevalence in Colombia represents an ongoing initiative to inform public policy actions. During the COVID-19 pandemic, there was a decrease in the number of autistic children served by the healthcare sector; however, the prevalence of ASD changed to higher levels in 2022. These findings contribute to strategies aimed at improving the quality of life for autistic individuals and mitigating the economic burden on their families.

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5. 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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6. Li L, Luo S, Zhang Y, Shang Q, Zhang W, Liu L, Zhang X, Mei S. [Genetic analysis of a child with Dias-Logan syndrome due to variant of BCL11A gene]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2024 (Sep 10);41(9):1096-1099.

OBJECTIVE: To analyze the clinical and genetic characteristics of a child featuring Dias-Logan syndrome. METHODS: A child with speech disorders and delayed psychomotor development from childhood who was admitted to the Rehabilitation Medicine Department of Children’s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the research subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Potential variant was screened by whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child has presented with global developmental delay, microcephaly, special facial features and behavioral problems. Genetic testing revealed a de novo variant of the BCL11A gene, namely c.561_567delACACGCA (p.Q187fs*7), which was classified as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The heterozygous variant of BCL11A gene probably underlay the Dias-Logan syndrome in this child. Above finding has enriched the phenotypic and mutational spectrum of the BCL11A gene and provides a basis for genetic counseling and clinical decision-making.

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7. Lin HY, Liang CS, Tsai SJ, Hsu JW, Huang KL, Su TP, Chen TJ, Bai YM, Hsu TW, Chen MH. Congenital hypothyroidism and risk of subsequent autism spectrum disorder and attention-deficit/hyperactivity disorder in Taiwan. Psychiatry Clin Neurosci;2024 (Sep 10)

AIM: Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT). METHODS: A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD. RESULTS: Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group. CONCLUSION: Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD.

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8. Norris JE, Harvey R, Hull L. Post-diagnostic support for adults diagnosed with autism in adulthood in the UK: A systematic review with narrative synthesis. Autism;2024 (Sep 10):13623613241273073.

More adults than ever before are seeking an autism diagnosis in adulthood. While receiving a diagnosis may be beneficial, many autistic people struggle to navigate their new diagnosis, and require support. This study conducted a systematic review of previous research on the support available after diagnosis (post-diagnostic support) for autistic adults without intellectual disability who were diagnosed in adulthood in the UK. A systematic review is a pre-planned method of searching for all relevant studies, before combining these to answer a larger question. The study aimed to investigate the availability of such support and its effectiveness, and to explore autistic adults’ experiences of accessing support. We also used publicly available information to create a map of the post-diagnostic support services currently available across the UK. A systematic search of seven databases was conducted, to identify UK-based studies published after 2012. Nineteen studies were eligible to be included in the study. Although some form of post-diagnostic support is available across most areas in the UK, this mostly consists of providing information and ‘signposting’ the person to other services. These options may not meet the needs of autistic people, who want services such as psychoeducation (therapy whereby an individual receives education about their diagnosis to improve understanding and self-management), and peer support. Findings highlight the need for adequate support to alleviate the post-diagnostic challenges autistic adults face. The study could not evaluate the effectiveness of support options in the UK due to a lack of information about this in published research. Research shows that autistic adults would like low-level support services, psychoeducation, and peer support, and may also prefer autistic-led support. Further research is required to develop and evaluate post-diagnostic support programmes which include these elements.

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9. Okuzumi S, Tei S, Itahashi T, Aoki YY, Hashimoto RI, Nakamura M, Takahashi H, Ohta H, Fujino J. Roles of empathy in altruistic cooperation in adults with and without autism spectrum disorder. Heliyon;2024 (Aug 30);10(16):e36255.

BACKGROUND: Altruistic cooperation (AC) is essential in human social interactions. Previous studies have investigated AC-related behavior in children with autism spectrum disorder (ASD), revealing that there is considerable individual variability in the behavior. However, this issue is still largely unexplored especially in the adult population. AIMS: To investigate individual differences in AC-related behavior, we conducted the resource allocation task (RAT) and modified version of the ultimatum game (mUG) among adults with and without ASD. METHODS AND PROCEDURES: The study employed a cross-sectional design, involving 27 adults with ASD (mean age 29.1 ± 4.3 years; three females) and 27 adults with typical development (TD) (mean age 25.8 ± 6.7 years; two females), who completed the RAT and mUG tasks. Beyond clinical characteristics, we assessed three primary psychological metrics: the interpersonal reactivity index (IRI), Barratt impulsiveness scale, and the behavioral inhibition and activation systems. OUTCOMES AND RESULTS: No significant differences were observed in the proportions of participants with high AC when assessed by RAT (p = 0.15) and mUG (p = 0.59) between the TD and ASD groups. Participants with high AC from the RAT demonstrated higher perspective-taking scores on the IRI than those with low AC within both the TD (p = 0.04) and ASD groups (p = 0.03). In the TD group, high AC individuals also scored higher on the IRI’s fantasy subscale as per the mUG (p = 0.03); however, this trend was not present in the ASD group. CONCLUSIONS AND IMPLICATIONS: The present findings indicate that empathy plays an important role in individual differences in AC-related behavior among adults with and without ASD, although the role could be different depending on the types of AC-related behavior between TD and ASD populations.

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10. Oliver LD, Moxon-Emre I, Hawco C, Dickie EW, Dakli A, Lyon RE, Szatmari P, Haltigan JD, Goldenberg A, Rashidi AG, Tan V, Secara MT, Desarkar P, Foussias G, Buchanan RW, Malhotra AK, Lai MC, Voineskos AN, Ameis SH. Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders. Mol Autism;2024 (Sep 4);15(1):37.

BACKGROUND: Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). METHODS: Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16-35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL’s PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted. RESULTS: ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance. LIMITATIONS: Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities. CONCLUSIONS: The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs.

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11. Percy AK, Ananth A, Neul JL. Rett Syndrome: The Emerging Landscape of Treatment Strategies. CNS Drugs;2024 (Sep 9)

Rett syndrome (RTT) has enjoyed remarkable progress in achieving specific therapies. RTT, a unique neurodevelopmental disorder first described in 1966, progressed slowly until the landmark paper of Hagberg and colleagues in 1983. Thereafter, rapid advances were achieved including the development of specific diagnostic criteria and the active search for a genetic etiology, resulting 16 years later in identification of variants in the methyl-CpG-binding protein (MECP2) gene located at Xq28. Shortly thereafter, the NIH Office of Rare Diseases funded the RTT Natural History Study (NHS) in 2003, initiating the acquisition of natural history data on clinical features from a large population of individuals with RTT. This information was essential for advancement of clinical trials to provide specific therapies for this disorder. In the process, the International Rett Syndrome Association (IRSA) was formed (now the International Rett Syndrome Foundation-IRSF), which participated directly in encouraging and expanding enrollment in the NHS and, subsequently, in developing the SCOUT program to facilitate testing of potential therapeutic agents in a mouse model of RTT. The overall objective was to review clinical characteristics developed from the NHS and to discuss the status of specific therapies for this progressive neurodevelopmental disorder. The NHS study provided critical information on RTT: growth, anthropometrics, longevity, key comorbidities including epilepsy, breath abnormalities, gastroesophageal dysfunction, scoliosis and other orthopedic issues, puberty, behavior and anxiety, and progressive motor deterioration including the appearance of parkinsonian features. Phenotype-genotype correlations were noted including the role of X chromosome inactivation. Development of clinical severity and quality of life measures also proved critical for subsequent clinical trials. Further, development of biochemical and neurophysiologic biomarkers offered further endpoints for clinical trials. Initial clinical trials prior to the NHS were ineffective, but advances resulting from the NHS and other studies worldwide promoted significant interest from pharmaceutical firms resulting in several clinical trials. While some of these have been unrewarding such as sarizotan, others have been quite promising including the approval of trofinetide by the FDA in 2023 as the first agent available for specific treatment of RTT. Blarcamesine has been trialed in phase 3 trials, 14 agents have been studied in phase 2 trials, and 7 agents are being evaluated in preclinical/translational studies. A landmark study in 2007 by Guy et al. demonstrated that activation of a normal MECP2 gene in a null mouse model resulted in significant improvement. Gene replacement therapy has advanced through translational studies to two current phase 1/2 clinical trials (Taysha102 and Neurogene-401). Additional genetic therapies are also under study including gene editing, RNA editing, and X-chromosome reactivation. Taken together, progress in understanding and treating RTT over the past 40 years has been remarkable. This suggests that further advances can be expected.

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12. Proteau-Lemieux M, Knoth IS, Davoudi S, Martin CO, Bélanger AM, Fontaine V, Côté V, Agbogba K, Vachon K, Whitlock K, Biag HMB, Thurman AJ, Rosenfelt C, Tassone F, Frei J, Capano L, Abbeduto L, Jacquemont S, Hessl D, Hagerman RJ, Schneider A, Bolduc F, Anagnostou E, Lippe S. Specific EEG resting state biomarkers in FXS and ASD. J Neurodev Disord;2024 (Sep 9);16(1):53.

BACKGROUND: Fragile X syndrome (FXS) and autism spectrum disorder (ASD) are neurodevelopmental conditions that often have a substantial impact on daily functioning and quality of life. FXS is the most common cause of inherited intellectual disability (ID) and the most common monogenetic cause of ASD. Previous literature has shown that electrophysiological activity measured by electroencephalogram (EEG) during resting state is perturbated in FXS and ASD. However, whether electrophysiological profiles of participants with FXS and ASD are similar remains unclear. The aim of this study was to compare EEG alterations found in these two clinical populations presenting varying degrees of cognitive and behavioral impairments. METHODS: Resting state EEG signal complexity, alpha peak frequency (APF) and power spectral density (PSD) were compared between 47 participants with FXS (aged between 5-20), 49 participants with ASD (aged between 6-17), and 52 neurotypical (NT) controls with a similar age distribution using MANCOVAs with age as covariate when appropriate. MANCOVAs controlling for age, when appropriate, and nonverbal intelligence quotient (NVIQ) score were subsequently performed to determine the impact of cognitive functioning on EEG alterations. RESULTS: Our results showed that FXS participants manifested decreased signal complexity and APF compared to ASD participants and NT controls, as well as altered power in the theta, alpha and low gamma frequency bands. ASD participants showed exaggerated beta power compared to FXS participants and NT controls, as well as enhanced low and high gamma power compared to NT controls. However, ASD participants did not manifest altered signal complexity or APF. Furthermore, when controlling for NVIQ, results of decreased complexity in higher scales and lower APF in FXS participants compared to NT controls and ASD participants were not replicated. CONCLUSIONS: These findings suggest that signal complexity and APF might reflect cognitive functioning, while altered power in the low gamma frequency band might be associated with neurodevelopmental conditions, particularly FXS and ASD.

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13. Reynolds KE, Napier M, Fei F, Green K, Scott AL. Dysregulated Purinergic Signalling in Fragile X Syndrome Cortical Astrocytes. Neuromolecular Med;2024 (Sep 10);26(1):36.

The symptoms of fragile X syndrome (FXS), caused by a single gene mutation to Fmr1, have been increasingly linked to disordered astrocyte signalling within the cerebral cortex. We have recently demonstrated that the purinergic signalling pathway, which utilizes nucleoside triphosphates and their metabolites to facilitate bidirectional glial and glial-neuronal interactions, is upregulated in cortical astrocytes derived from the Fmr1 knockout (KO) mouse model of FXS. Heightened Fmr1 KO P2Y purinergic receptor levels were correlated with prolonged intracellular calcium release, elevated synaptogenic protein secretion, and hyperactivity of developing circuits. However, due to the relative lack of sensitive and reproducible quantification methods available for measuring purines and pyrimidines, determining the abundance of these factors in Fmr1 KO astrocytes was limited. We therefore developed a hydrophilic interaction liquid chromatography protocol coupled with mass spectrometry to compare the abundance of intracellular and extracellular purinergic molecules between wildtype and Fmr1 KO mouse astrocytes. Significant differences in the concentrations of UDP, ATP, AMP, and adenosine intracellular stores were found within Fmr1 KO astrocytes relative to WT. The extracellular level of adenosine was also significantly elevated in Fmr1 KO astrocyte-conditioned media in comparison to media collected from WT astrocytes. Glycosylation of the astrocyte membrane-bound CD39 ectonucleotidase, which facilitates ligand breakdown following synaptic release, was also elevated in Fmr1 KO astrocyte cultures. Together, these differences demonstrated further dysregulation of the purinergic signalling system within Fmr1 KO cortical astrocytes, potentially leading to significant alterations in FXS purinergic receptor activation and cellular pathology.

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14. Roels S, Begeer S, Scheeren AM, van Prooijen JW. Conspiracy mentality in autistic and non-autistic individuals. Cogn Neuropsychiatry;2024 (Sep 10):1-14.

BACKGROUND: Belief in conspiracy theories has emerged across times and cultures. While previous accounts attributed conspiracy beliefs to mental health conditions, accumulating research suggests that conspiracy theories are common among the general population. In the present study we examined whether conspiracy mentality – that is, a general predisposition to believe conspiracy theories – differed between a group of autistic adults and a general population sample. METHODS: This study included an autistic sample (n = 682) and a general population sample (n = 4358). Participants’ conspiracy mentality was measured using the Conspiracy Mentality Questionnaire (CMQ). RESULTS: A one-way ANCOVA (controlling for participants’ age, gender, educational level, and ethnicity) revealed no difference in conspiracy mentality between an autism and a community sample. CONCLUSIONS: The current study suggests that being autistic, or having more autistic traits, does not predict conspiracy mentality. These findings underscore that autism does not predispose people to conspiracy theories and suggest that autism is neither a risk factor for, nor a protective factor against, conspiracy mentality.

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15. Shi Q, Wu L, Ren B, Guo K, Jiang YH, Zhang YQ, Hu L. Impaired tactile processing in autism-associated Shank3 mutant dogs: neural mechanism and intervention. Sci Bull (Beijing);2024 (Sep 10)

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16. Shingleton-Smith C, Koudys J, Azzano A, Feldman M. Telehealth general case parent training for children at risk for autism. J Appl Behav Anal;2024 (Sep 9)

Parent-mediated interventions for infants and young children with an increased likelihood of autism may help ameliorate developmental concerns; however, generalization of parents’ teaching strategies to novel child target skills has not been consistently demonstrated. This study expanded our parent training program, Parent Intervention for Children at-Risk for Autism (PICARA), by incorporating telehealth general case training (PICARA-TGCT) to promote generalization of teaching skills. Five parent-child dyads participated. Child target skills were chosen from the categories of imitation, receptive language, and expressive language. A concurrent multiple-baseline-across-participants design was used to evaluate the effect of training across two cohorts of parent-child dyads. Dependent variables included the percentage of correct parent teaching skills and the percentage of child correct responses. Parent teaching skills increased across all participants for both trained and untrained child target skills, as did child skills. This study provides support for PICARA-TGCT as an efficacious and efficient early intervention model.

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17. Skjeldal OH, Posserud MB. Autism or Sukhareva’s syndrome?. Tidsskr Nor Laegeforen;2024 (Sep 10);144(10)

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18. Thurman AJ, Nunnally AD, Nguyen V, Berry-Kravis E, Sterling A, Edgin J, Hamilton D, Aschkenasy J, Abbeduto L. Short-term and Long-term Stability of the Autism Diagnostic Observation Schedule (ADOS-2) Calibrated Comparison Scores (CCS) and Classification Scores in Youth with Down Syndrome or Fragile X Syndrome with Intellectual Disability. J Autism Dev Disord;2024 (Sep 9)

Autism diagnosis in individuals with fragile X syndrome (FXS) or Down syndrome (DS) with co-occurring intellectual disability is complex since clinicians often must consider other co-occurring behavioral features. Understanding how best to assess the features of autism in individuals with these conditions is crucial. In this study, we consider the short-term and long-term psychometric consistency of the Autism Diagnostic Observation Schedule-2 (ADOS-2) calibrated comparison scores (CCSs) and ASD classifications in individuals with FXS or DS. 76 individuals with DS (39 males; M(age) = 15.27) and 90 individuals with FXS (71 males; M(age) = 14.52 years) completed an assessment battery (ADOS-2, abbreviated IQ assessment and semi-structured language sample) at three timepoints (initial visit, short-term stability visit, long-term stability visit). All CCSs were found to have short-and long-term consistency for both groups, with lowest reliability scores for the repetitive behaviors (RRB) CCSs. Decreased reliability of RRB CCSs was found in the DS group than the FXS group. Variable short- and long-term ASD classifications were observed in both groups, with significantly higher variability in the DS group. Across groups, participants with variable classifications had lower ADOS-2 CCSs and higher language scores than those with stable ASD classifications. In the FXS group, those with variable classifications earned higher cognitive scores than did participants with stable ASD classifications. These findings highlight the high incidence of autism symptomatology in individuals with DS or FXS and co-occurring intellectual disability, while elucidating the short- and long-term variability of symptom expression in the context of structured observational tasks such as the ADOS-2.

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19. Waddington H, Jordan P, Hammond M, Tupou J, Patrick L, Macaskill E, Davies G, Pillar S, van der Meer L, Whitehouse AJO. Low-intensity parent- and clinician-delivered support for young autistic children in Aotearoa New Zealand: a randomised controlled trial. Lancet Reg Health West Pac;2024 (Oct);51:101173.

BACKGROUND: Aotearoa New Zealand does not provide publicly-funded intensive autism support. While parent-mediated supports are promising, children and families may also benefit from direct clinician support. We tested the efficacy of a low-intensity programme involving parent- and clinician-delivered support for autistic children. METHODS: This single-blind, two-arm randomised controlled trial assessed outcomes of a six-month low-intensity parent- and clinician-delivered support (2-3 h per week) based on the Early Start Denver Model compared to a control group who received monthly support calls and assistance with referrals. Children aged 1-4.5 years who were autistic or showing signs of autism and their parents were randomised to the low-intensity or control group by a blinded statistician using the Urn minimisation method. Assessments were conducted at baseline and immediately following the support period (24-weeks post-baseline). The primary outcome was child engagement during an interaction with their parent. The trial was pre-registered with ANZCTR: U1111-1260-2529. FINDINGS: From March 2021 to May 2023, 56 families were randomised to either the low-intensity or control group. Following drop-outs, 21 families in the low-intensity group and 24 in the control group were included in analysis. There was large and significantly greater improvement in children’s engagement in the low-intensity group compared to the control group (F (1, 43) = 21.47, p < 0.0001, η(p) (2) = 0.33). There was one recorded adverse event unrelated to the support and two adverse effects related to the support. INTERPRETATION: A low-intensity parent- and clinician-delivered support can improve engagement between an autistic child and their parent during play. Low-intensity supports may be beneficial in areas where access to clinical autism supports is limited. FUNDING: Emerging Researcher First Grant from the Health Research Council of New Zealand.

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20. Wankhede N, Kale M, Shukla M, Nathiya D, R R, Kaur P, Goyanka B, Rahangdale S, Taksande B, Upaganlawar A, Khalid M, Chigurupati S, Umekar M, Kopalli SR, Koppula S. Leveraging AI for the diagnosis and treatment of autism spectrum disorder: Current trends and future prospects. Asian J Psychiatr;2024 (Sep 10);101:104241.

The integration of artificial intelligence (AI) into the diagnosis and treatment of autism spectrum disorder (ASD) represents a promising frontier in healthcare. This review explores the current landscape and future prospects of AI technologies in ASD diagnostics and interventions. AI enables early detection and personalized assessment of ASD through the analysis of diverse data sources such as behavioural patterns, neuroimaging, genetics, and electronic health records. Machine learning algorithms exhibit high accuracy in distinguishing ASD from neurotypical development and other developmental disorders, facilitating timely interventions. Furthermore, AI-driven therapeutic interventions, including augmentative communication systems, virtual reality-based training, and robot-assisted therapies, show potential in improving social interactions and communication skills in individuals with ASD. Despite challenges such as data privacy and interpretability, the future of AI in ASD holds promise for refining diagnostic accuracy, deploying telehealth platforms, and tailoring treatment plans. By harnessing AI, clinicians can enhance ASD care delivery, empower patients, and advance our understanding of this complex condition.

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21. Willim J, Woike D, Greene D, Das S, Pfeifer K, Yuan W, Lindsey A, Itani O, Böhme AL, Tibbe D, Hönck HH, Hassani Nia F, Zech M, Brunet T, Faivre L, Sorlin A, Vitobello A, Smol T, Colson C, Baranano K, Schatz K, Bayat A, Schoch K, Spillmann R, Davis EE, Conboy E, Vetrini F, Platzer K, Neuser S, Gburek-Augustat J, Grace AN, Mitchell B, Stegmann A, Sinnema M, Meeks N, Saunders C, Cadieux-Dion M, Hoyer J, Van-Gils J, de Sainte-Agathe JM, Thompson ML, Bebin EM, Weisz-Hubshman M, Tabet AC, Verloes A, Levy J, Latypova X, Harder S, Silverman GA, Pak SC, Schedl T, Freson K, Mumford A, Turro E, Schlein C, Shashi V, Kreienkamp HJ. Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors. Nat Commun;2024 (Sep 10);15(1):7909.

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca(2+)/calmodulin-dependent protein kinase II. We have previously observed an association between high impact variants in LRRC7 and Intellectual Disability; also three individual cases with variants in LRRC7 had been described. We identify here 33 individuals (one of them previously described) with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in LRRC7. The clinical spectrum involves intellectual disability, autism, ADHD, aggression and, in several cases, hyperphagia-associated obesity. A PDZ domain variant interferes with synaptic targeting of Densin-180 in primary cultured neurons. Using in vitro systems (two hybrid, BioID, coimmunoprecipitation of tagged proteins from 293T cells) we identified new candidate interaction partners for the LRR domain, including protein phosphatase 1 (PP1), and observed that variants in the LRR reduced binding to these proteins. We conclude that LRRC7 encodes a major determinant of intellectual development and behaviour.

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22. Yu Y, Lu J, Li H, Gao Y, Ye X, Zhang X, Lu J, Qiu J. [Clinical phenotype and genetic analysis of a rare case with 6p duplication and terminal deletion syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2024 (Sep 10);41(9):1117-1123.

OBJECTIVE: To explore the genetic basis for a child with developmental delay and intellectual deficit (DD/ID). METHODS: A child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3, 2023 due to DD/ID, craniofacial malformations, and recurrent infections of upper respiratory tract was selected as the study subject. G-banded chromosomal karyotyping was carried out for the child and her parents. Low-depth genome-wide copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) were used to screen for genome-wide copy number variations (CNV), and fluorescence in situ hybridization (FISH) was used to verify the origin of candidate CNV. RESULTS: The child, an 8-year-old girl, had featured unexplained growth and intellectual development delay, multiple craniofacial malformations, and recurrent infections of the upper respiratory tract. She was found to have a karyotype of 46,XX,der(6)add(6)(q23), while both of her parents were normal. Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25. FISH verified that both the duplication and deletion had occurred de novo. CONCLUSION: The abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.

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23. Zhang S, Zhou Y, Shen J, Wang Y, Xia J, Li C, Liu W, Hayat K, Qian M. Early-Life Exposure to 4-Hydroxy-4′-Isopropoxydiphenylsulfone Induces Behavioral Deficits Associated with Autism Spectrum Disorders in Mice. Environ Sci Technol;2024 (Sep 10);58(36):15984-15996.

Exposure to bisphenol A (BPA) during gestation and lactation is considered to be a potential risk factor for autism spectrum disorder (ASD) in both humans and animals. As a novel alternative to BPA, 4-hydroxy-4′-isopropoxydiphenylsulfone (BPSIP) is frequently detected in breast milk and placental barrier systems, suggesting potential transmission from the mother to offspring and increased risk of exposure. Gestation and lactation are critical periods for central nervous system development, which are vulnerable to certain environmental pollutants. Herein, we investigated the behavioral impacts and neurobiological effects of early-life exposure to BPSIP (0.02, 0.1, and 0.5 mg/kg body weight/day) in mice offspring. Behavioral studies indicated that BPSIP exposure induced ASD-like behaviors, including elevated anxiety-related behavior and decreased spatial memory, in both male and female pups. A distinct pattern of reduced social novelty was observed only in female offspring, accompanied by significant alterations in antioxidant levels. Transcriptome analysis demonstrated that differentially expressed genes (DEGs) were mainly enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, a decrease in the protein levels of complex IV (COX IV) across all tested populations suggests a profound impact on mitochondrial function, potentially leading to abnormal energy metabolism in individuals with autism. Additionally, changes in synaptic proteins, evidenced by alterations in synapsin 1 (SYN1) and postsynaptic density protein-95 (PSD95) levels in the cerebellum and hippocampus, support the notion of synaptic involvement. These findings suggest that BPSIP may induce sex-specific neurotoxic effects that involve oxidative stress, energy generation, and synaptic plasticity.

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24. Zheng N, Luo S, Zhang X, Hu L, Huang M, Li M, McCaig C, Ding YQ, Lang B. Haploinsufficiency of intraflagellar transport protein 172 causes autism-like behavioral phenotypes in mice through BDNF. J Adv Res;2024 (Sep 10)

INTRODUCTION: Primary cilia are hair-like solitary organelles growing on most mammalian cells that play fundamental roles in embryonic patterning and organogenesis. Defective cilia often cause a suite of inherited diseases called ciliopathies with multifaceted manifestations. Intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium, actively facilitates the formation and absorption of primary cilia. IFT172 is the largest component of the IFT-B complex, and its roles in Bardet-Biedl Syndrome (BBS) have been appreciated with unclear mechanisms. OBJECTIVES: We performed a battery of behavioral tests with Ift172 haploinsufficiency (Ift172(+/-)) and WT littermates. We use RNA sequencing to identify the genes and signaling pathways that are differentially expressed and enriched in the hippocampus of Ift172(+/-) mice. Using AAV-mediated sparse labeling, electron microscopic examination, patch clamp and local field potential recording, western blot, luciferase reporter assay, chromatin immunoprecipitation, and neuropharmacological approach, we investigated the underlying mechanisms for the aberrant phenotypes presented by Ift172(+/-) mice. RESULTS: Ift172(+/-) mice displayed excessive self-grooming, elevated anxiety, and impaired cognition. RNA sequencing revealed enrichment of differentially expressed genes in pathways relevant to axonogenesis and synaptic plasticity, which were further confirmed by less spine density and synaptic number. Ift172(+/-) mice demonstrated fewer parvalbumin-expressing neurons, decreased inhibitory synaptic transmission, augmented theta oscillation, and sharp-wave ripples in the CA1 region. Moreover, Ift172 haploinsufficiency caused less BDNF production and less activated BDNF-TrkB signaling pathway through transcription factor Gli3. Application of 7,8-Dihydroxyflavone, a potent small molecular TrkB agonist, fully restored BDNF-TrkB signaling activity and abnormal behavioral phenotypes presented by Ift172(+/-) mice. With luciferase and chip assays, we provided further evidence that Gli3 may physically interact with BDNF promoter I and regulate BDNF expression. CONCLUSIONS: Our data suggest that Ift172 per se drives neurotrophic effects and, when defective, could cause neurodevelopmental disorders reminiscent of autism-like disorders.

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