1. Ataíde SS, Ferreira JP, Campos MJ. Prescription of Exercise Programs for Individuals with Autism Spectrum Disorder: Systematic Review. J Autism Dev Disord;2024 (Sep 21)

Physical exercise offers health benefits for individuals with autism spectrum disorder (ASD). However, the literature on recommendations for exercise prescription is still limited. This study aims to identify the most beneficial type of exercise program and present the most effective guidelines for its prescription in individuals with ASD. A systematic review was carried out using the ERIC, Web of Science, PsycINFO, PubMed and Scopus databases in accordance with the PRISMA guidelines. Of a total of 1114 studies, 18 were considered eligible. Overall, the type of programs included aerobic exercise sessions with an average duration of 12 weeks, with 3 weekly sessions of 45 to 60 min. The assessment included the shuttle test protocol, the progressive cardiovascular endurance running protocol and the modified Bruce protocol. For the muscle strength exercises, the sessions lasted an average of 12 weeks, with 2 weekly sessions of 10 to 20 min, including 2 to 4 exercises, 1 to 3 sets, with 6 to 12 repetitions. The assessments included the handgrip strength test, the modified curve-up test and the push-up test. The programs had positive effects on cardiorespiratory capacity and hemodynamics, indicating that the benefits of training increase when both capacities are combined. This study provides useful guidelines for adapted sports coaches to prescribe exercise programs aimed at promoting quality of life in individuals with ASD.

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2. Bahram Sangani N, Koetsier J, Gomes AR, Diogo MM, Fernandes TG, Bouwman FG, Mariman ECM, Ghazvini M, Gribnau J, Curfs LMG, Reutelingsperger CP, Eijssen LMT. Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids. Cell Mol Life Sci;2024 (Sep 21);81(1):410.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by de novo mutations in the MECP2 gene. Although miRNAs in extracellular vesicles (EVs) have been suggested to play an essential role in several neurological conditions, no prior study has utilized brain organoids to profile EV-derived miRNAs during normal and RTT-affected neuronal development. Here we report the spatiotemporal expression pattern of EV-derived miRNAs in region-specific forebrain organoids generated from female hiPSCs with a MeCP2:R255X mutation and the corresponding isogenic control. EV miRNA and protein expression profiles were characterized at day 0, day 13, day 40, and day 75. Several members of the hsa-miR-302/367 cluster were identified as having a time-dependent expression profile with RTT-specific alterations at the latest developmental stage. Moreover, the miRNA species of the chromosome 14 miRNA cluster (C14MC) exhibited strong upregulation in RTT forebrain organoids irrespective of their spatiotemporal location. Together, our results suggest essential roles of the C14MC and hsa-miR-302/367 clusters in EVs during normal and RTT-associated neurodevelopment, displaying promising prospects as biomarkers for monitoring RTT progression.

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3. Beradze M, Meir N. Disfluencies as a Window into Pragmatic Skills in Russian-Hebrew Bilingual Autistic and Non-Autistic Children. J Autism Dev Disord;2024 (Sep 19)

There is little research on the production of speech disfluencies such as silent pauses, repetitions, self-corrections, and filled pauses (e.g., eh, em) in monolingual autistic children, and there is no data on this crucial part of speech production in bilingual autistic children. This study aims to address this gap by examining disfluency production in bilingual autistic and non-autistic children across two linguistically distinct languages, HL-Russian (the home language) and SL-Hebrew (the societal language). Fifty-one bilingual Russian-Hebrew-speaking autistic and non-autistic children aged 5-9 (autistic: n = 21; non-autistic: n = 30), matched for age and non-verbal intelligence, participated in picture-based story-generation tasks (LITMUS MAIN, Gagarina et al., ZAS Papers in Linguistics, 63:1-36, 2019). Audio recordings of narrative samples were transcribed, coded, and scored for eleven disfluency types using CLAN tools. The non-autistic group produced higher overall disfluency rate than the autistic group. The autistic group exhibited fewer filled and silent pauses than the non-autistic group in HL-Russian. Furthermore, non-autistic children manifested varied distribution of disfluency types across languages, while autistic children displayed more consistent patterns across languages. In summary, we replicated findings from previous research on monolinguals only partly, as no between-group difference in filled pauses was found in SL-Hebrew. Additionally, bilingual autistic children exhibited language-universal patterns of disfluency production, whereas their non-autistic peers displayed language-specific patterns.

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4. 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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5. 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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6. Kroupi E, Jh Jones E, Oakley B, Buitelaar J, Charman T, Loth E, Murphy D, Soria-Frisch A. Age-related differences in delta-beta phase-amplitude coupling in autistic individuals. Clin Neurophysiol;2024 (Aug 23);167:74-83.

OBJECTIVE: We aim to investigate the relationship between the core symptoms of autism, anxiety levels, and attention deficit hyperactivity disorder (ADHD) traits, and a non-autism-specific, neurophysiological metric, the Delta-Beta phase-amplitude coupling (PAC), extracted from the resting-state EEG for autistic and non-autistic populations across three different age groups (children, adolescents, and adults). METHODS: We analyze the eyes-open resting-state EEG of 371 individuals. We applied a phase de-biasing PAC algorithm expected to result in a more accurate PAC estimate than other PAC methodologies available in the literature. RESULTS: In the adult group, we found a significant increase of the delta-beta PAC in the autistic subgroup who met the Autism Diagnostic Observation Schedule-2 (ADOS-2) Autism Diagnostic Interview-Revised (ADR-R) ADOS-2/ADI-R threshold compared to non-autistic individuals. The differences seem age-specific since we found no statistically significant differences in the children and adolescent populations. Moreover, we found a significant positive correlation with the restricted and repetitive behaviours score of the ADOS-2 diagnostic instrument and with ADHD hyperactivity/impulsivity in the entire autistic cohort. CONCLUSIONS: The neurophysiological differences we found only in the autistic individuals that meet the thresholds also point out the need for future studies that look for autistic neurodiverse subgroups beyond age. SIGNIFICANCE: The delta-beta debiasing PAC (dPAC) may potentially serve as a severity biomarker in the autistic population.

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7. O’Shea A, Cersosimo R, Engelhardt PE. Online Metaphor Comprehension in Adults with Autism Spectrum Disorders: An Eye Tracking Study. J Autism Dev Disord;2024 (Sep 21)

The aim of this study was to investigate novel metaphor comprehension in adults with autism spectrum disorder (ASD). Previous literature is conflicting about whether individuals with ASD have impairment in this particular type of figurative language. Participants in the study completed a visual world paradigm eye-tracking task, which involved selecting an interpretation of an auditorily presented sentence (i.e. a picture-sentence matching task), where images corresponded to literal and metaphorical interpretations. Thus, the study also investigated online processing, via reaction times and eye movements. Forty adults participated in the study (18 with ASD and 22 typically-developing controls). Each participant completed the AQ questionnaire and had their vocabulary assessed. Results showed that participants with ASD comprehended metaphorical utterances with the same accuracy as controls. However, they had significantly slower reaction times, and specifically, were approximately 800 ms slower. Analysis of eye movements revealed that participants with ASD showed significantly longer fixation times on both the target and distractor image, the latter of which suggests difficulty overcoming the literal interpretation. Consistent with some prior studies, we showed that adults with ASD are not impaired in novel metaphor comprehension, but they were clearly less efficient. Verbal abilities did not significantly relate to performance. Finally, our online processing measure (eye tracking) provided us with insights into the nature of the ASD inefficiency (i.e. a literality bias).

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8. Pittas E, Warreyn P. Introduction to the Special Issue: The post-COVID-19 psychological and educational effects on the home and school lives of students with developmental disabilities. Res Dev Disabil;2024 (Sep 19);154:104847.

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9. 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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10. 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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11. Walsh O, Linehan C, Ryan C. Is there evidence that playing games promotes social skills training for autistic children and youth?. Autism;2024 (Sep 21):13623613241277309.

There is growing interest in using games to help autistic children and youth learn social skills. However, there is no clear agreement on the best way to design these games to ensure they are most effective. In our research, we reviewed studies that used games to teach social skills to autistic children and youth. We aimed to describe the different types of games, identify which ones were most successful and understand the psychological methods used. We searched five databases and found 3070 studies, which we narrowed down to 17 that met our criteria. Each of these 17 studies reported that their game helped improve social skills in autistic children. Interestingly, all these studies used some form of technology, even though this was not a requirement. However, we noticed that many studies were not clear on what specific social skills they were targeting or how they defined ‘social skills’. For future work, we suggest that game-based interventions should be more clearly based on established theories. In addition, it is important to involve autistic people in the design of these games to ensure they meet their needs effectively.

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