1. Correction to: « Development of a sexual consent intervention for adolescents with intellectual and developmental disabilities ». J Appl Res Intellect Disabil;2024 (Nov);37(6):e13294.

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2. Brauer B, Ancatén-González C, Ahumada-Marchant C, Meza RC, Merino-Veliz N, Nardocci G, Varela-Nallar L, Arriagada G, Chávez AE, Bustos FJ. Impact of KDM6B mosaic brain knockout on synaptic function and behavior. Sci Rep;2024 (Sep 2);14(1):20416.

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.

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3. Bryers A, Hawkes CA, Parkin E, Dawson N. Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders. Biochem Soc Trans;2024 (Sep 2)

Autism spectrum disorders (ASD) are a heterogenous set of syndromes characterised by social impairment and cognitive symptoms. Currently, there are limited treatment options available to help people with ASD manage their symptoms. Understanding the biological mechanisms that result in ASD diagnosis and symptomatology is an essential step in developing new interventional strategies. Human genetic studies have identified common gene variants of small effect and rare risk genes and copy number variants (CNVs) that substantially increase the risk of developing ASD. Reverse translational studies using rodent models based on these genetic variants provide new insight into the biological basis of ASD. Here we review recent findings from three ASD associated CNV mouse models (16p11.2, 2p16.3 and 22q11.2 deletion) that show behavioural and cognitive phenotypes relevant to ASD. These models have identified disturbed excitation-inhibition neurotransmitter balance, evidenced by dysfunctional glutamate and GABA signalling, as a key aetiological mechanism. These models also provide emerging evidence for serotoninergic neurotransmitter system dysfunction, although more work is needed to clarify the nature of this. At the brain network level, prefrontal cortex (PFC) dysfunctional connectivity is also evident across these models, supporting disturbed PFC function as a key nexus in ASD aetiology. Overall, published data highlight the utility and valuable insight gained into ASD aetiology from preclinical CNV mouse models. These have identified key aetiological mechanisms that represent putative novel therapeutic targets for the treatment of ASD symptoms, making them useful translational models for future drug discovery, development and validation.

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4. Ferraguto C, Piquemal-Lagoueillat M, Lemaire V, Moreau MM, Trazzi S, Uguagliati B, Ciani E, Bertrand SS, Louette E, Bontempi B, Pietropaolo S. Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome. Neuropsychopharmacology;2024 (Sep 2)

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and autistic-like symptoms such as social deficits. Despite considerable efforts, effective pharmacological treatments are still lacking, prompting the need for exploring the therapeutic value of existing drugs beyond their original approved use. One such repurposed drug is chlorzoxazone which is classified as a large-conductance calcium-dependent potassium (BKCa) channel opener. Reduced BKCa channel functionality has been reported in FXS patients, suggesting that molecules activating these channels could serve as promising treatments for this syndrome. Here, we sought to characterize the therapeutic potential of chlorzoxazone using the Fmr1-KO mouse model of FXS which recapitulates the main phenotypes of FXS, including BKCa channel alterations. Chlorzoxazone, administered either acutely or chronically, rescued hyperactivity and acoustic hyper-responsiveness as well as impaired social interactions exhibited by Fmr1-KO mice. Chlorzoxazone was more efficacious in alleviating these phenotypes than gaboxadol and metformin, two repurposed treatments for FXS that do not target BKCa channels. Systemic administration of chlorzoxazone modulated the neuronal activity-dependent gene c-fos in selected brain areas of Fmr1-KO mice, corrected aberrant hippocampal dendritic spines, and was able to rescue impaired BKCa currents recorded from hippocampal and cortical neurons of these mutants. Collectively, these findings provide further preclinical support for BKCa channels as a valuable therapeutic target for treating FXS and encourage the repurposing of chlorzoxazone for clinical applications in FXS and other related neurodevelopmental diseases.

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5. Holubowsky L, Kernreiter J, Blaha S, Kautz I, Krsmanovic I, Schuster M, Shakenova L. [Not Available]. Prax Kinderpsychol Kinderpsychiatr;2024 (Aug);73(5):416-431.

Autism in Systemic Group Psychotherapy: « Strong Together » a Care Model for Children and Adolescents from Practice Awareness of people with autism in our society is constantly increasing. Nevertheless, ambiguities and caution in dealing with autistic clients are still tangible. Due to the growing demand, there is a shortage of care for clients on the autism spectrum. This applies in particular to group therapy services in German-speaking countries. However, the international AWMF guidelines state that group therapy is the therapy method of choice for children and adolescents with autistic perception. In order to counteract this gap in care, this article presents a systemic group therapy for autistic people. It explains the extent to which the systemic approach in combination with a multimodal approach is a beneficial approach. It also highlights the importance of expanding the range of care services, interdisciplinary cooperation, and exchange. The compatibility of practice and research in systemic psychotherapy will be explained, teamwork in private practice will be emphasized, therapeutic experiences will be shared and an outlook on ongoing evaluation research will be presented.

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6. Khaliulin I, Hamoudi W, Amal H. The multifaceted role of mitochondria in autism spectrum disorder. Mol Psychiatry;2024 (Sep 2)

Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions. Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD. The aberrant functioning of this organelle is of such high importance that ASD has been proposed as a mitochondrial disease. It should be noted that aerobic energy production is not the only function of the mitochondria. In particular, these organelles are involved in the regulation of Ca(2+) homeostasis, different mechanisms of programmed cell death, autophagy, and reactive oxygen and nitrogen species (ROS and RNS) production. Several syndromes originated from mitochondria-related mutations display ASD phenotype. Abnormalities in Ca(2+) handling and ATP production in the brain mitochondria affect synaptic transmission, plasticity, and synaptic development, contributing to ASD. ROS and Ca(2+) regulate the activity of the mitochondrial permeability transition pore (mPTP). The prolonged opening of this pore affects the redox state of the mitochondria, impairs oxidative phosphorylation, and activates apoptosis, ultimately leading to cell death. A dysregulation between the enhanced mitochondria-related processes of apoptosis and the inhibited autophagy leads to the accumulation of toxic products in the brains of individuals with ASD. Although many mitochondria-related mechanisms still have to be investigated, and whether they are the cause or consequence of this disorder is still unknown, the accumulating data show that the breakdown of any of the mitochondrial functions may contribute to abnormal brain development leading to ASD. In this review, we discuss the multifaceted role of mitochondria in ASD from the various aspects of neuroscience.

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7. Li C, He WQ. Prevalence and treatment of autism spectrum disorder in the United States, 2016-2022. Autism Res;2024 (Sep 2)

This study aims to assess the prevalence of Autism Spectrum Disorder (ASD) and its treatment. The study population was children aged 3-17 years with information on current ASD from National Survey of Children’s Health, 2016-2022. Analysis of treatment was also conducted within the population of children with a current ASD diagnosis. A multivariate log-binomial regression model was used to assess the change of current ASD prevalence and ASD treatment by two study period (prior to COVID-19 pandemic: 2016-2019; during COVID-19 pandemic: 2020-22) and sociodemographic information. Compared to the current ASD at 2.5% in 2016, it increased to 3.6% in 2022. The treatment has decreased from 70.5% in 2016 to 61.6% in 2022 for any treatment and from 27.2% in 2016 to 20.4% in 2022 for medication treatment. Compared to children from 2016-2019, children from the following group were more likely to have ASD diagnosis during the pandemic (2020-2022), including those aged 3-5 years (aPR = 1.66, 95%CI 1.29-2.13), non-Hispanic white children, children from family with above national family income, and those with private insurance. However, medication treatment almost halved during the pandemic for non-Hispanic black children (aPR = 0.49, 95%CI 0.26-0.93) and children born overseas. In conclusion, higher prevalence of ASD might indicate a better awareness of ASD. The reduction in treatment correlates to the health service disruption caused by the pandemic, highlighting the needs of policy efforts to improve treatment for ASD.

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8. Liao A, Zheng W, Wang S, Wang N, Li Y, Chen D, Wang Y. Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats. CNS Neurosci Ther;2024 (Sep);30(9):e70015.

INTRODUCTION: Neuroinflammation and microglial activation-related dendritic injury contribute to the pathogenesis of Autism Spectrum Disorder (ASD). Previous studies show that Progranulin (PGRN) is a growth factor associated with inflammation and synaptic development, but the role of PGRN in autism and the mechanisms underlying changes in PGRN expression remain unclear. AIMS: To investigate the impact of PGRN in autism, we stereotactically injected recombinant PGRN into the hippocampus of ASD model rats. Additionally, we explored the possibility that sortilin may be the factor behind the alterations in PGRN by utilizing SORT1 knockdown. Ultimately, we aimed to identify potential targets for the treatment of autism. RESULTS: PGRN could alleviate inflammatory responses, protect neuronal dendritic spines, and ameliorate autism-like behaviors. Meanwhile, elevated expression of sortilin and decreased levels of PGRN were observed in both ASD patients and rats. Enhanced sortilin levels facilitated PGRN internalization into lysosomes. Notably, suppressing SORT1 expression amplified PGRN levels, lessened microglial activation, and mitigated inflammation, thereby alleviating autism-like behaviors. CONCLUSION: Collectively, our findings highlight elevated sortilin levels in ASD rat brains, exacerbating dendrite impairment by affecting PGRN expression. PGRN supplementation and SORT1 knockdown hold potential as therapeutic strategies for ASD.

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9. Rangosch A, Duarte VE, Quiñones MA. Interatrial Septum Assessment by Transthoracic Echocardiography Part 1: Secundum ASD. Methodist Debakey Cardiovasc J;2024;20(1):77-79.

This 10-minute video aims at improving skills for the structural assessment of the interatrial septum using 2-dimensional transthoracic echocardiography (TTE) to increase the ability to diagnose-or rule out-the different types of interatrial communications. Of the five types of lesions, this video focuses on ostium secundum atrial septal defect. This is the first video in our MicroLearning Video Series, designed to help a target audience of sonographers, general cardiologists, general practitioners who want to gain knowledge on fundamental cardiology, and technicians. View the video at https://vimeo.com/989145537/4898c3c590.

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10. Sánchez Pedroche A, Valera-Pozo M, Mateus Moreno A, Lara Díaz MF, Aguilar-Mediavilla E, Adrover-Roig D. Is language impaired in Spanish-speaking children with autism spectrum disorder level 1?. Autism Dev Lang Impair;2024 (Jan-Dec);9:23969415241275931.

The current diagnostic criteria for the autism spectrum disorder (ASD) include the possibility to specify concomitant language difficulties. PURPOSE: Our main aim was to explore whether children with ASD-Level 1 (ASD-L1) present difficulties in the acquisition of structural language, as little work has been done in this regard so far. As a secondary aim we evaluated the degree to which the potential language impairment in ASD is directly associated with their social communication deficits or it represents a distinct deficit. METHODS: To further clarify the nature and characteristics of putative language difficulties in ASD-L1, we evaluated language skills in 89 children and preadolescents diagnosed with ASD-L1, and a group of typically developing participants (TD). All of them were between 8 and 13 years old and had similar socioeconomic backgrounds. RESULTS: Children with ASD-L1 obtained lower scores than those in TD group in repeating sentences, in finding the semantic relationships between words, and in applying word structure rules (morphology). Congruently, the core language standard score was lower in the ASD-L1 group, and the proportion of language delay was significantly higher in the ASD-L1 group than in the control group. CONCLUSION: Language scores were associated with autistic traits; thus, language performance in ASD-L1 is closely related to autistic symptoms. These results are discussed according to the literature on linguistic deficits in ASD-L1 and their relations with phonological working memory.

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11. Sandham V, Hill AE, Hinchliffe F, Armstrong RM. The translatability of communication interventions in paediatric autism: A scoping review. Int J Speech Lang Pathol;2024 (Sep 1):1-13.

PURPOSE: Translation of research is requisite for speech-language pathologists; however, barriers have been reported. This review aimed to identify the extant literature published on communication for autistic children, and examine the replicability and translatability of communication interventions for speech-language pathologists providing services to children with autism. METHOD: A scoping review was conducted using a six-stage protocol. Following initial database searching and screening, data were extracted from included studies for demographic characteristics and Template for Intervention Description and Replication (TIDieR) checklist elements. Stakeholder consultation interviews with 13 speech-language pathologists who work with autistic children were also undertaken. RESULT: The database search revealed 4719 studies on the topic of communication in autistic children, of which 762 were communication intervention studies. Of these included intervention studies, 30% were considered replicable according to the TIDieR checklist. Stakeholder consultation revealed that poorly described intervention studies hindered translation efforts. CONCLUSION: The vast amount of autism communication intervention literature and the variable quality of intervention description reporting are barriers to accessing high quality literature for translation to practice. Improved reporting of intervention descriptions in autism communication intervention studies would support research translation into clinical settings.

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12. Tong X, Xie H, Fonzo GA, Zhao K, Satterthwaite TD, Carlisle NB, Zhang Y. Symptom dimensions of resting-state electroencephalographic functional connectivity in autism. Nat Ment Health;2024 (Mar);2(3):287-298.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by social and communication deficits (SCDs), restricted and repetitive behaviors (RRBs) and fixated interests. Despite its prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To comprehensively explore these heterogeneities, we developed a new analytical framework combining contrastive learning and sparse canonical correlation analysis that identifies symptom-linked resting-state electroencephalographic connectivity dimensions within 392 ASD samples. We present two dimensions with multivariate connectivity basis exhibiting significant correlations with SCD and RRB, confirm their robustness through cross-validation and demonstrate their conceptual generalizability using an independent dataset (n = 222). Specifically, the right inferior parietal lobe is the core region for RRB, while connectivity between the left angular gyrus and the right middle temporal gyrus show key contribution to SCD. These findings provide a promising avenue to parse ASD heterogeneity with high clinical translatability, paving the way for ASD treatment development and precision medicine.

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13. Xie L, Li H, Xiao M, Chen N, Zang X, Liu Y, Ye H, Tang C. Epigenetic insights into Fragile X Syndrome. Front Cell Dev Biol;2024;12:1432444.

Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder closely associated with intellectual disability and autism spectrum disorders. The core of the disease lies in the abnormal expansion of the CGG trinucleotide repeat sequence at the 5’end of the FMR1 gene. When the repetition exceeds 200 times, it causes the silencing of the FMR1 gene, leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). Although the detailed mechanism by which the CGG repeat expansion triggers gene silencing is yet to be fully elucidated, it is known that this process does not alter the promoter region or the coding sequence of the FMR1 gene. This discovery provides a scientific basis for the potential reversal of FMR1 gene silencing through interventional approaches, thereby improving the symptoms of FXS. Epigenetics, a mechanism of genetic regulation that does not depend on changes in the DNA sequence, has become a new focus in FXS research by modulating gene expression in a reversible manner. The latest progress in molecular genetics has revealed that epigenetics plays a key role in the pathogenesis and pathophysiological processes of FXS. This article compiles the existing research findings on the role of epigenetics in Fragile X Syndrome (FXS) with the aim of deepening the understanding of the pathogenesis of FXS to identify potential targets for new therapeutic strategies.

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14. Yaseen YA, Saleem AMT, Bari DS, Nayef RT, Yacoob Aldosky HY. Evaluating mental chronometry as a quantitative measure of information processing in early childhood autism. Appl Neuropsychol Child;2024 (Sep 2):1-7.

OBJECTIVES: Mental chronometry is the scientific study of cognitive processing speed measured by reaction time (RT), which is the elapsed time between the onset of a stimulus and an individual’s response. This study aims at measuring the RT among young children with autism spectrum disorders (ASD) and comparing it with normal (typically developing) children. METHODS: 60 ASD children were selected from different ASD centers, and 60 normal children were selected from different kindergartens for participation in this study. Participants were aged 3-6 years old. The RT was measured using the Fitlight trainer device. The findings were statistically evaluated using independent t-tests and ANOVA tests. RESULT: Significant differences (p < 0.0001) were found between both groups in all tasks, and ASD children demonstrated slower RT compared to the normal group. The RT measured through three senses (visual, auditory, and touch) for ASD and normal were 3.64 ± 2.16, 13.19 ± 2.41(trial), 1835.23 ± 757.95, 697.12 ± 87.83 (second), and 1550.89 ± 499.76, 752.67 ± 124.02 (second) respectively. CONCLUSION: The evaluated RT showed significant impairment in RT among ASD in comparison to normal children and this was true for the three senses. The Fitlight trainer could be used to assess RT and stimulus-response among ASD children in various cognitive tasks. Similar studies, involving larger samples from different areas and involving other sense organs, are indicated to confirm the results.

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15. Ziva A, Ziori E. EXPRESS: Implicit learning in children and adolescents with and without autism spectrum disorders: Exploring the effects of individual differences. Q J Exp Psychol (Hove);2024 (Sep 2):17470218241281639.

Implicit learning plays an important role in the acquisition of various skills that are often deficient in individuals with autism spectrum disorder (ASD). The present study examines the implicit learning ability of children and adolescents with ASD, by comparing it to that of a typical group of peers, using the Artificial Grammar Learning (AGL) task. Additionally, this study investigates whether the above ability is associated with individual characteristics, namely, intelligence quotient (IQ), ASD symptoms severity, and individual perception style (global/holistic or local/focused). The sample consisted of 20 individuals with mild to relatively severe ASD symptoms and 20 age- and gender-matched typically developing individuals (TD). The unconscious (implicit) nature of learning was assessed via a subjective measure, the « no loss gambling » method, which allows an unbiased evaluation of the confidence accompanying each judgement. The results provided evidence of implicit learning, which was preserved in the ASD group, although reduced relative to the typical group. Multiple linear regressions with interaction terms between Group and participants’ scores on the Wechsler Abbreviated Scale of Intelligence (WASI), the Childhood Autism Rating Scale (CARS), and performance on a Navon-type task examined whether the possible relationships between each of the above scores and AGL and implicit learning differ in the two groups. Implicit learning was not significantly associated with IQ, ASD symptoms severity or individual perception style (except for perception style in terms of RTs for the TD group). These results confirm and extend earlier findings supporting the resilience of implicit learning to individual differences.

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