1. Chowdhury TA, Luy DA, Scapellato G, Farache D, Lee ASY, Quinn CC. Ortholog of autism candidate gene RBM27 regulates mitoribosomal assembly factor MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment. PLoS Biol;2024 (Oct 31);22(10):e3002876.

Mitochondrial dysfunction is thought to be a key component of neurodevelopmental disorders such as autism, intellectual disability, and attention-deficit hyperactivity disorder (ADHD). However, little is known about the molecular mechanisms that protect against mitochondrial dysfunction during neurodevelopment. Here, we address this question through the investigation of rbm-26, the Caenorhabditis elegans ortholog of the RBM27 autism candidate gene, which encodes an RNA-binding protein whose role in neurons is unknown. We report that RBM-26 (RBM26/27) protects against axonal defects by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Autism-associated missense variants in RBM-26 cause a sharp decrease in RBM-26 protein expression along with defects in axon overlap and axon degeneration that occurs during larval development. Using a biochemical screen, we identified the mRNA for the MALS-1 mitoribosomal assembly factor as a binding partner for RBM-26. Loss of RBM-26 function causes a dramatic overexpression of mals-1 mRNA and MALS-1 protein. Moreover, genetic analysis indicates that this overexpression of MALS-1 is responsible for the mitochondrial and axon degeneration defects in rbm-26 mutants. These observations reveal a mechanism that regulates expression of a mitoribosomal assembly factor to protect against axon degeneration during neurodevelopment.

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2. Cosgrove KT, Middleton C, Thompson TG, Be B, DeVries L. « It’s Really Complicated »: Engaging Key Stakeholders to Inform a Novel Parent-led Sexual Health Education Program for Autistic Youth. J Autism Dev Disord;2024 (Nov 2)

Autistic adolescents frequently encounter difficulties in managing changes associated with puberty, sexuality, and relationships, and parents may be a useful source of sexual and reproductive health education (SRE) for this population. Despite this, few evidence-based programs exist to support parents in this role. Thus, there is a need for the development of such programs, particularly those incorporating the lived experiences of key stakeholders. The present qualitative investigation aimed to determine the SRE needs of autistic youth and to inform a novel, parent-led SRE program. Data were collected through semi-structured interviews conducted with two rounds of focus groups with two stakeholder groups: parents of autistic children (N = 4) and adult autistic self-advocates (N = 4). Focus groups were recorded and transcribed verbatim. The research team conducted rapid qualitative analysis on all four transcripts, and major findings were summarized and triangulated across groups. Four overarching themes were identified: « Empower parents as educators, » « Individualize supports and education, » « Consider cultural and intersecting identities, » and « Prioritize safety. » Parents can serve a primary role in providing SRE to autistic youth and would likely benefit from participating in a tailored program that prioritizes safety and considers the influence of culture and other aspects of identity on content delivery. Future research on the implementation of such a program is needed.

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3. Gormley J, Brittlebank S, Light J. Exploring the communication access and participation of a young adult with autism spectrum disorder with limited speech and inpatient nursing staff. Disabil Rehabil Assist Technol;2024 (Nov 3):1-9.

This study aimed to describe the nature of interactions between health care professionals and a young adult with autism spectrum disorder with limited speech during an inpatient stay. An observational study was conducted to describe the interactions between a young adult on the autism spectrum and 14 of his inpatient health care providers. Naturalistic video-recordings were taken, and behavioral coding was completed to measure the frequency and type of communication turns taken. The providers took 93% of conversational turns. Most provider turns (76%) were non-obligatory in nature and did not invite the young adult to engage in turn-taking. The young adult only had access to his communication system during one of the 27 interactions (4%); however, when he had access to his system, he demonstrated higher levels of turn-taking. Health care providers should offer patients with limited speech more communicative turns, provide adequate wait time, and ensure communication systems are available during all inpatient interactions. Inpatient health care providers dominated interactions with a young adult with autism and limited speech.Most inpatient health care provider turns did not present an opportunity for the patient to respond.The young adultcould not access his communication system for most interactions. eng

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4. Makhijani A, Jenkins N, Kaufman J, Hoq M, Priestley S, Elia S, McKenzie I, Davidson A, Leong P, Lazzaro T, McNab S, Danchin M. Virtual reality for routine immunisations in needle phobic children with and without developmental disabilities: A pilot study. Vaccine;2024 (Nov 1);42(26):126481.

Virtual reality for routine immunisations in needle phobic children with and without developmental disabilities: a pilot study. BACKGROUND: Virtual Reality (VR) headsets can improve needle procedure success and experiences for children, but they have not been evaluated to support immunisation in children with anxiety and behavioural challenges. This study assessed the feasibility and acceptability of VR for immunisation in children with needle phobia, including children with and without developmental disabilities. METHODS: A mixed method pilot study was conducted at the Royal Children’s Hospital, Melbourne. Children with needle phobia aged 4-14 years scheduled for immunisation with distraction and conscious sedation were eligible. VR was offered to children with needle anxiety and/or developmental disabilities before and during immunisation in addition to standard care. Children and caregivers completed electronic surveys pre- and post-immunisation, followed by qualitative interviews post-immunisation. Clinicians completed post-immunisation surveys. Primary outcomes were feasibility and acceptability of VR according to children, caregivers and clinicians. RESULTS: Between May and December 2022, we screened 54 children and included 30; 15 with and 15 without developmental disability. Preparation to use VR took less than five minutes for most children (24/30; 80 %). Twenty nine (96 %) used VR immediately before immunisation, and 17 (57 %) continued using it during immunisation (7 with developmental disability, 10 without). Twenty seven (90 %) children were immunised successfully, with a small reduction in required sedation. Of those who used VR during immunisation, 16/17 (94 %) reported a more positive overall experience. Of those who only used VR before immunisation, 3/13 (23 %) still reported benefit. VR was therefore described as beneficial for 19/30 (63 %) participants (9 with developmental disability, 10 without). Caregivers reported willingness to use VR in future immunisation encounters for 23/30 (77 %) children (11 with developmental disability, 12 without). DISCUSSION: This pilot study suggests VR was feasible and acceptable for many children with needle phobia, both with and without developmental disability. These findings will inform a randomised controlled trial to assess effectiveness.

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5. Nakamura T, Nagayama H, Sasada S. Development and Validation of the Participation Questionnaire for Preschoolers with Autism Spectrum Disorder: Structural Validity, Internal Consistency, and Construct Validity. Phys Occup Ther Pediatr;2024 (Nov 3):1-16.

AIM: This study aimed to develop the Participation Questionnaire for Preschoolers (PQP) and validate its psychometric properties as a disability-specific tool designed to assess participation in preschool-aged children with autism spectrum disorder (ASD). METHODS: This cross-sectional study recruited caregivers of 412 children, including those diagnosed with ASD and those at risk for neurodevelopmental disorders. Participants were recruited from child development facilities, medical institutions, and developmental support websites across Japan. Data from 287 children diagnosed with ASD were analyzed for item reduction, followed by exploratory factor analysis and the calculation of Cronbach’s alpha to evaluate internal consistency. Five hypotheses were tested to assess construct validity. RESULTS: Item reduction resulted in the removal of seven items and the identification of four factors: Friendship and Education, Family Satisfaction, Daily Living and Independence, and Leisure and Community Life. Cronbach’s alpha values for these factors ranged from 0.74 to 0.88, indicating acceptable internal consistency. Three of the five hypotheses related to construct validity were supported, aligning with expectations. CONCLUSION: The PQP exhibited structural validity, internal consistency, and construct validity. However, further longitudinal studies are needed to validate its measurement properties over time.

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6. Niu X, Huang F, Lyu H, Liu J, Zhang X, Bian J, Gao Z, Liu B. The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice. J Mol Neurosci;2024 (Oct 31);74(4):103.

Chromodomain helicase DNA-binding 8 (CHD8) is a gene that poses a high risk for autism spectrum disorder (ASD) and neurological development delay. Nevertheless, the impact of CHD8 haploinsufficiency on both hippocampus neurogenesis and behavior remains uncertain. Here, we performed behavioral assessments on male and female CHD8 heterozygous mice. The study discovered that both male and female CHD8 heterozygous mice displayed an impairment in preference for social novelty. Concurrently, CHD8 heterozygous mice exhibited anxiety-like behavior. However, its cognitive capacity for learning and memory is within the expected range. Furthermore, we discovered a reduction in the number of both immature and mature new neurons in mice with CHD8 heterozygous, resulting in an impeded neurogenesis process in the hippocampus. Taken together, our findings indicate that CHD8 plays a crucial role in the regulation of hippocampal neurogenesis, and further suggest that ASD-like behaviors observed in CHD8 heterozygous mice may be associated with disruptions in hippocampal neurogenesis.

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7. Norris JE, Berry-Kravis EM, Harnett MD, Reines SA, Reese MA, Outterson AH, Michalak C, Furman J, Gurney ME, Ethridge LE. Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome. Mol Autism;2024 (Nov 2);15(1):47.

Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5′ untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS.

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8. Poli F, Koolen M, Velázquez-Vargas CA, Ramos-Sanchez J, Meyer M, Mars RB, Rommelse N, Hunnius S. Autistic traits foster effective curiosity-driven exploration. PLoS Comput Biol;2024 (Oct);20(10):e1012453.

Curiosity-driven exploration involves actively engaging with the environment to learn from it. Here, we hypothesize that the cognitive mechanisms underlying exploratory behavior may differ across individuals depending on personal characteristics such as autistic traits. In turn, this variability might influence successful exploration. To investigate this, we collected self- and other-reports of autistic traits from university students, and tested them in an exploration task in which participants could learn the hiding patterns of multiple characters. Participants’ prediction errors and learning progress (i.e., the decrease in prediction error) on the task were tracked with a hierarchical delta-rule model. Crucially, participants could freely decide when to disengage from a character and what to explore next. We examined whether autistic traits modulated the relation of prediction errors and learning progress with exploration. We found that participants with lower scores on other-reports of insistence-on-sameness and general autistic traits were less persistent, primarily relying on learning progress during the initial stages of exploration. Conversely, participants with higher scores were more persistent and relied on learning progress in later phases of exploration, resulting in better performance in the task. This research advances our understanding of the interplay between autistic traits and exploration drives, emphasizing the importance of individual traits in learning processes and highlighting the need for personalized learning approaches.

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