1. Barnhardt E, Coury DL. Family-systems interventions for families of people with an intellectual disability or who are autistic show potential, but further research is needed. Evid Based Nurs;2024 (Sep 20);27(4):148.

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2. Cosentino L, Urbinati C, Lanzillotta C, De Rasmo D, Valenti D, Pellas M, Quattrini MC, Piscitelli F, Kostrzewa M, Di Domenico F, Pietraforte D, Bisogno T, Signorile A, Vacca RA, De Filippis B. Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome. Mol Autism;2024 (Sep 19);15(1):39.

BACKGROUND: Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations in the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), the primary receptor subtype of the endocannabinoid system in the brain, is located on brain mitochondrial membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission and memory abilities through the inhibition of the intra-mitochondrial protein kinase A (mtPKA). In the present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie the brain mitochondrial alterations in RTT and whether its modulation by systemic administration of the CB1R inverse agonist rimonabant might improve bioenergetics and cognitive defects in mice modeling RTT. METHODS: Rimonabant (0.3 mg/kg/day, intraperitoneal injections) was administered daily to symptomatic female mice carrying a truncating mutation of the Mecp2 gene and its effects on brain mitochondria functionality, systemic oxidative status, and memory function were assessed. RESULTS: mtCB1R is overexpressed in the RTT mouse brain. Subchronic treatment with rimonabant normalizes mtCB1R expression in RTT mouse brains, boosts mtPKA signaling, and restores the defective brain mitochondrial bioenergetics, abnormal peripheral redox homeostasis, and impaired cognitive abilities in RTT mice. LIMITATIONS: The lack of selectivity of the rimonabant treatment towards mtCB1R does not allow us to exclude that the beneficial effects exerted by the treatment in the RTT mouse model may be ascribed more broadly to the modulation of CB1R activity and distribution among intracellular compartments, rather than to a selective effect on mtCB1R-mediated signaling. The low sample size of few experiments is a further limitation that has been addressed replicating the main findings under different experimental conditions. CONCLUSIONS: The present data identify mtCB1R overexpression as a novel molecular alteration in the RTT mouse brain that may underlie defective brain mitochondrial bioenergetics and cognitive dysfunction.

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3. 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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4. Eid L, Lokmane L, Raju PK, Tene Tadoum SB, Jiang X, Toulouse K, Lupien-Meilleur A, Charron-Ligez F, Toumi A, Backer S, Lachance M, Lavertu-Jolin M, Montseny M, Lacaille JC, Bloch-Gallego E, Rossignol E. Both GEF domains of the autism and developmental epileptic encephalopathy-associated Trio protein are required for proper tangential migration of GABAergic interneurons. Mol Psychiatry;2024 (Sep 19)

Recessive and de novo mutations in the TRIO gene are associated with intellectual deficiency (ID), autism spectrum disorder (ASD) and developmental epileptic encephalopathies (DEE). TRIO is a dual guanine nucleotide exchange factor (GEF) that activates Rac1, Cdc42 and RhoA. Trio has been extensively studied in excitatory neurons, and has recently been found to regulate the switch from tangential to radial migration in GABAergic interneurons (INs) through GEFD1-Rac1-dependent SDF1α/CXCR4 signaling. Given the central role of Rho-GTPases during neuronal migration and the implication of IN pathologies in ASD and DEE, we investigated the relative roles of both Trio’s GEF domains in regulating the dynamics of INs tangential migration. In Trio(-/-) mice, we observed reduced numbers of tangentially migrating INs, with intact progenitor proliferation. Further, we noted increased growth cone collapse in developing INs, suggesting altered cytoskeleton dynamics. To bypass the embryonic mortality of Trio(-/-) mice, we generated Dlx5/6(Cre);Trio(c/c) conditional mutant mice (Trio(cKO)), which develop spontaneous seizures and behavioral deficits reminiscent of ASD and ID. These phenotypes are associated with reduced cortical IN density and functional cortical inhibition. Mechanistically, this reduction of cortical IN numbers reflects a premature switch to radial migration, with an aberrant early entry in the cortical plate, as well as major deficits in cytoskeletal dynamics, including enhanced leading neurite branching and slower nucleokinesis reflecting reduced actin filament condensation and turnover as well as a loss of response to the motogenic effect of EphA4/ephrin A2 reverse signaling. Further, we show that both Trio GEFD1 and GEFD2 domains are required for proper IN migration, with a dominant role of the RhoA-activating GEFD2 domain. Altogether, our data show a critical role of the DEE/ASD-associated Trio gene in the establishment of cortical inhibition and the requirement of both GEF domains in regulating IN migration dynamics.

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5. El-Monshed AH, Loutfy A, El-Boraie H, Eweida RS, Fayed SM, El-Gazar HE, Ali Zoromba M. Feasibility and Preliminary Evaluation of Theory-Based Training Program on Daily Living Skills Among Children With Autism Spectrum Disorder: Findings From Rural Regions in Egypt. J Am Psychiatr Nurses Assoc;2024 (Sep 20):10783903241279376.

BACKGROUND: One of the most crucial objectives in the education and treatment of young children with autism spectrum disorder (ASD) is independence in daily living skills (DLS). Therefore, as a child with ASD condition grows, measures of everyday functioning including adaptive behaviors should be more regularly monitored and regulated. AIM: The primary aim of this study was to evaluate the feasibility of a developed theory-based training program and its preliminary effectiveness on the acquisition of DLS among school-age children with ASD. METHODS: A preliminary experimental research design (pre- and post-evaluation) was conducted from the beginning of May to the end of July 2023 on 31 children with ASD. The socio-economic status scale, Vineland Adaptive Behavior Scale, and Gilliam Autism Rating Scale were administered before and after a theory-based DLS training program. RESULTS: There was a significant difference in the DLS and motor functioning before and after the implementation of the training program (p < .001 and p = .021, respectively). In addition, there was a significant difference in the total score of autistic severity before and after the implementation of the training program (p < .001). CONCLUSION: The promising outcomes of the study indicate the need for further testing and expansion of this intervention. These findings contribute to the growing body of evidence highlighting the significance of DLS training program in the comprehensive treatment approach for children with ASD. Consequently, proposing DLS training programs as a cost-effective and efficient nursing intervention is warranted.

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6. Francis K, Alshammari N, Alsulaihim N, Aboukhamseen S, El Dardiri M, AlRashidi F, Ridha HA, Al-Hassan M, Terzi A. The use of formal language as a strong sign of verbal autistic children in diglossic communities: The case of Arabic. Autism Res;2024 (Sep 20)

The current study aimed to investigate whether the use of formal language (Modern Standard Arabic [MSA]) by young children in diglossic Arab communities offers diagnostic insights, especially for verbal autistic children and to further explore this phenomenon. We used a cohort study design, with 4-6-year-old fluent first language Arabic-speaking children attending Arabic Kindergartens in two representative Kuwait governates. Reported cases for MSA use were assessed via a computer-based structured language test and corroborated cases were further assessed for exposure to sources of MSA, verbal IQ, temperamental characteristics, and autism spectrum disorder (ASD). Four children from the same class without developmental difficulties were selected for each MSA user as control group. The frequency of MSA use among verbal pre-schoolers was 0.46%. Use of MSA did not correlate with parents’ education, amount of exposure to MSA, verbal IQ, but with severity of ASD. Predicted probability of ASD in the presence of MSA was 0.86. Executive functions of ASD-MSA users were similar to those of the control group and significantly higher than unselected autistic peers in the literature. The use of MSA has the potential to serve as a strong sign for the diagnosis of verbal autistic children, often missed or delayed in being diagnosed. We also discuss strategies via which language is acquired in ASD.

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7. Frasca A, Miramondi F, Butti E, Indrigo M, Balbontin Arenas M, Postogna FM, Piffer A, Bedogni F, Pizzamiglio L, Cambria C, Borello U, Antonucci F, Martino G, Landsberger N. Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway. EMBO Mol Med;2024 (Sep 20)

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analyzed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.

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8. He X, Yang Y, Zhou S, Wei Q, Zhou H, Tao J, Yang G, You M. Alterations in microbiota-metabolism-circRNA crosstalk in autism spectrum disorder-like behaviours caused by maternal exposure to glyphosate-based herbicides in mice. Ecotoxicol Environ Saf;2024 (Sep 17);285:117060.

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

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9. Mertz L. Using AI and ML to Predict Autism Spectrum Disorder. IEEE Pulse;2024 (Sep-Oct);15(3):11-15.

Autism spectrum disorder is a condition that showcases the potential usefulness of artificial intelligence (AI) and machine learning (ML). This is an area of great need, according to Dennis Wall, Ph.D., professor of pediatrics and biomedical data science at Stanford University in California. « ASD diagnostics is crying out for a solution that’s faster, more equitable, and more quantitative. This is where biomedical data science can really help, »he said.

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10. Novielli P, Romano D, Magarelli M, Diacono D, Monaco A, Amoroso N, Vacca M, De Angelis M, Bellotti R, Tangaro S. Personalized identification of autism-related bacteria in the gut microbiome using explainable artificial intelligence. iScience;2024 (Sep 20);27(9):110709.

Autism spectrum disorder (ASD) affects social interaction and communication. Emerging evidence links ASD to gut microbiome alterations, suggesting that microbial composition may play a role in the disorder. This study employs explainable artificial intelligence (XAI) to examine the contributions of individual microbial species to ASD. By using local explanation embeddings and unsupervised clustering, the research identifies distinct ASD subgroups, underscoring the disorder’s heterogeneity. Specific microbial biomarkers associated with ASD are revealed, and the best classifiers achieved an AU-ROC of 0.965 ± 0.005 and an AU-PRC of 0.967 ± 0.008. The findings support the notion that gut microbiome composition varies significantly among individuals with ASD. This work’s broader significance lies in its potential to inform personalized interventions, enhancing precision in ASD management and classification. These insights highlight the importance of individualized microbiome profiles for developing tailored therapeutic strategies for ASD.

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11. Prahl A. The Effects of Functional Reading Activities to Motivate and Empower for Autistic Young Adults: A Single-Case Design Study. Am J Speech Lang Pathol;2024 (Sep 20):1-18.

PURPOSE: The purpose of this study was to examine the effects of Functional Reading Activities to Motivate and Empower (FRAME) on use of reading comprehension strategies in intellectually and/or developmentally disabled young adults. METHOD: A single-case, multiple-probe design across functional literacy stimuli (e.g., text messages, e-mails) was replicated across three intellectually or developmentally disabled 23- to 26-year-old young adults, all of whom had a primary diagnosis of autism. Within FRAME, reading comprehension strategies were taught and practiced within the context of functional texts or activities of daily living that involve written language (e.g., text messages, e-mails). Each session followed the teach-model-coach-review approach and was conducted via telepractice. Participants’ use of reading comprehension strategies was measured in baseline, intervention, maintenance, and with generalization probes. RESULTS: Visual analysis of the data indicated a functional relation between FRAME and the use of reading comprehension strategies for two of the three autistic young adults. All participants maintained increased use of reading comprehension strategies post-intervention. CONCLUSIONS: This study provides preliminary evidence that FRAME is associated with improved use of reading comprehension strategies that maintains over time. Thus, FRAME has the potential to support continued improvement of functional reading skills throughout the lifespan, which is critical as autistic individuals make the transition from adolescence to adult life. Further research is needed to evaluate the effects of the intervention on more distal outcomes of written language and to examine how to best tailor the intervention to individual differences to optimize outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26882422.

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12. Richdale AL, Shui AM, Lampinen LA, Katz T. Sleep disturbance and other co-occurring conditions in autistic children: A network approach to understanding their inter-relationships. Autism Res;2024 (Sep 20)

Autistic children frequently have one or more co-occurring psychological, behavioral, or medical conditions. We examined relationships between child behaviors, sleep, adaptive behavior, autistic traits, mental health conditions, and health in autistic children using network analysis. Network analysis is hypothesis generating and can inform our understanding of relationships between multiple conditions and behaviors, directing the development of transdiagnostic treatments for co-occurring conditions. Participants were two child cohorts from the Autism Treatment Network registry: ages 2-5 years (n = 2372) and 6-17 years (n = 1553). Least absolute-shrinkage and selection operator (LASSO) regularized partial correlation network analysis was performed in the 2-5 years cohort (35 items) and the 6-17 years cohort (36 items). The Spinglass algorithm determined communities within each network. Two-step expected influence (EI2) determined the importance of network variables. The most influential network items were sleep difficulties (2 items) and aggressive behaviors for young children and aggressive behaviors, social problems, and anxious/depressed behavior for older children. Five communities were found for younger children and seven for older children. Of the top three most important bridge variables, night-waking/parasomnias and anxious/depressed behavior were in both age-groups, and somatic complaints and sleep initiation/duration were in younger and older cohorts respectively. Despite cohort differences, sleep disturbances were prominent in all networks, indicating they are a transdiagnostic feature across many clinical conditions, and thus a target for intervention and monitoring. Aggressive behavior was influential in the partial correlation networks, indicating a potential red flag for clinical monitoring. Other items of strong network importance may also be intervention targets or screening flags.

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13. Saeliw T, Kanlayaprasit S, Thongkorn S, Songsritaya K, Sanannam B, Jindatip D, Hu VW, Sarachana T. Investigation of chimeric transcripts derived from LINE-1 and Alu retrotransposons in cerebellar tissues of individuals with autism spectrum disorder (ASD). Sci Rep;2024 (Sep 19);14(1):21889.

LINE-1 and Alu retrotransposons are components of the human genome and have been implicated in many human diseases. These elements can influence human transcriptome plasticity in various mechanisms. Chimeric transcripts derived from LINE-1 and Alu can also impact the human transcriptome, such as exonization and post-transcriptional modification. However, its specific role in ASD neuropathology remains unclear, particularly in the cerebellum tissues. We performed RNA-sequencing of post-mortem cerebellum tissues from ASD and unaffected individuals for transposable elements profiling and chimeric transcript identification. The majority of free transcripts of transposable elements were not changed in the cerebellum tissues of ASD compared with unaffected individuals. Nevertheless, we observed that chimeric transcripts derived from LINE-1 and Alu were embedded in the transcripts of differentially expressed genes in the cerebellum of ASD, and these genes were related to developments and abnormalities of the cerebellum. In addition, the expression levels of these genes were correlated with the significantly decreased thickness of the molecular layer in the cerebellum of ASD. We also found that global methylation and expression of LINE-1 and Alu elements were not changed in ASD, but observed in the ASD sub-phenotypes. Our findings showed associations between transposable elements and cerebellar abnormalities in ASD, particularly in distinct phenotypic subgroups. Further investigations using appropriate models are warranted to elucidate the structural and functional implications of LINE-1 and Alu elements in ASD neuropathology.

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14. Sarr R, Spain D, Quinton AMG, Happé F, Brewin CR, Radcliffe J, Jowett S, Miles S, González RA, Albert I, Scholwin A, Stirling M, Markham S, Strange S, Rumball F. Differential diagnosis of autism, attachment disorders, complex post-traumatic stress disorder and emotionally unstable personality disorder: A Delphi study. Br J Psychol;2024 (Sep 20)

Individuals diagnosed with autism, attachment disorders, emotionally unstable personality disorder (EUPD) or complex post-traumatic stress disorder (CPTSD) can present with similar features. This renders differential and accurate diagnosis of these conditions difficult, leading to diagnostic overshadowing and misdiagnosis. The purpose of this study was to explore professionals’ perspectives on the differential diagnosis of autism, attachment disorders and CPTSD in young people; and of autism, CPTSD and EUPD in adults. A co-produced three-round Delphi study gathered information through a series of questionnaires from 106 international professionals with expertise in assessing and/or diagnosing at least one of these conditions. To provide specialist guidance and data triangulation, working groups of experts by experience, clinicians and researchers were consulted. Delphi statements were considered to have reached consensus if at least 80% of participants were in agreement. Two hundred and seventy-five Delphi statements reached consensus. Overlapping and differentiating features, methods of assessment, difficulties encountered during differential diagnosis and suggestions for improvements were identified. The findings highlight current practices for differential diagnosis of autism, attachment disorders, CPTSD and EUPD in young people and adults. Areas for future research, clinical and service provision implications, were also identified.

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15. Toral-Lopez J, Gonzalez-Huerta LM. Novel 10q21.1-q22.1 duplication in a boy with minor facial dysmorphism, mild intellectual disability, autism spectrum disorder -like phenotype, and short stature. Cytogenet Genome Res;2024 (Sep 20):1-11.

INTRODUCTION: Duplications reported in 10q21-q22 include borderline to moderate intellectual disability, growth retardation, autism, attention deficit hyperactivity disorder, and minor craniofacial dysmorphism. CASE PRESENTATION: We present a patient with a novel 14.7 Mb de novo interstitial duplication at 10q21.1-q22.1 delineated by a high-definition (HD) single nucleotide polymorphism (SNP) array. The boy had minor facial dysmorphism, mild intellectual disability, an autism spectrum disorder-like phenotype, and short stature. CONCLUSION: This is the first case in which a novel 10q21.1-q22.1 duplication was detected by HD SNP array, expanding the spectrum of duplications seen in 10q21-q22. This report provides a detailed clinical examination of a patient with a 10q21.1-q22.1 duplication and suggests that brain development and cognitive function may be affected by an increased dosage sensitivity of the involved JMJD1C and EGR2 genes. This case contributes to the understanding of the genotype-phenotype relationship for genetic counselling and provides further evidence for the identification of a novel microduplication syndrome in 10q21-q22.

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16. Zhou S, Chen Z, Liu G, Ma L, Liu Y. High autistic traits linked with reduced performance on affective task switching: An ERP study. Neuroimage;2024 (Sep 17);300:120855.

Few studies have investigated affective flexibility in individuals with high autistic traits. In the present study, we employed affective task-switching paradigm combined with event related potential (ERP) technology to explore affective flexibility in individuals with high autistic traits. Participants were instructed to switch between identifying the gender (gender task) and emotion (emotion task) of presented faces. Two groups of participants were recruited based on the Autism Spectrum Quotient (AQ) scores: a High Autistic Group (HAG) and a Low Autistic Group (LAG). The results confirmed that the HAG exhibited greater behavioral emotion switch costs and increased N2 and decreased P3 components when switching to the emotion task. Additionally, we identified an affective asymmetric switch cost in the HAG, where the switch cost for the emotion task was larger than for the gender task at both behavioral and electrophysiological levels. In contrast, a symmetrical switch cost was observed in the LAG. These findings indicate that the HAG experiences difficulties with affective flexibility, particularly in tasks involving emotional processing. The patterns of affective asymmetric switch costs observed in both groups differed from previous results in autistic children and the general population, suggesting that the relative dominance of gender and emotion tasks may vary between the two groups. We propose that the dominance of emotion tasks declines as autistic traits increase.

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