1. Choudhary A, Rosh I, Hussein Y, Netser S, Shemen A, Suliman T, Rike WA, Simchi L, Shklyar B, Abu-Akel A, Zinger A, Offen D, Wagner S, Stern S. Extracellular vesicles from stem cells rescue cellular phenotypes and behavioral deficits in SHANK3-associated ASD neuronal and mouse models. Cell Death Dis;2026 (Feb 22)

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that mediate intercellular communication by transferring diverse cargoes, including RNA and proteins. SHANK3, a synaptic scaffolding protein critical for synapse structure and function, is implicated in autism spectrum disorder (ASD) and Phelan-McDermid Syndrome (PMS). Early hyperexcitability in cortical neurons is a characterized endophenotype in ASD. Here, we investigated EV-mediated effects in the context of SHANK3 deficiency using human iPSC-derived cortical neurons and Shank3B-/- mice. Switching EVs between SHANK3 mutant and control neurons revealed that SHANK3 mutant-derived EVs transferred the hyperexcitability and accelerated maturation phenotypes to control neurons. Proteomic analysis revealed enrichment of synaptic structural regulators (e.g., ACTB, CFL1, AGRN, and CLSTN1) in SHANK3 mutant neuron-derived EVs. This is consistent with known actin cytoskeletal dysregulation driven by SHANK3 deficiency. However, control neuron-derived EVs failed to rescue mutant phenotypes, likely due to their decreased enrichment of synaptic proteins and related pathways. Further, EVs from mesenchymal stem cells (MSCs) and healthy donor iPSCs, containing synaptic modulators such as complement proteins (C1R, C1S), plasticity-associated proteins (MDK, IGFBP3), and homeostatic regulators (FGF2, SFRP1), rescued the hyperexcitability and normalized the maturation in SHANK3 mutant neurons. In addition, intranasal administration of iPSC-derived EVs in Shank3B-/- mice significantly rescued ASD-like behavioral deficits, emphasizing their therapeutic potential. Together, these findings reveal a novel EV-mediated mechanism for modulating dysregulated excitability and synaptic maturation, addressing a critical unmet need in ASD and associated neurodevelopmental disorders.

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2. Hansford RLW, Wilson B, Griffiths R, Mahar AL. Factors Associated With the Receipt of Female Breast Cancer Treatment Among People Living With Intellectual or Developmental Disabilities: A Population-Based Retrospective Cohort Study. J Intellect Disabil Res;2026 (Feb 22)

BACKGROUND: People with intellectual or developmental disabilities (IDD) experience breast cancer care inequities relative to those without IDD. Identifying factors associated with receipt of breast cancer treatment among those with IDD is needed to provide guidance and inform resources for improving patient-centred care. This study explores factors associated with receipt of breast cancer treatment among individuals with IDD. METHODS: We conducted a population-based retrospective cohort study with administrative health data in Ontario, Canada. Adults with IDD diagnosed with Stage I-III female breast cancer between 2007 and 2018 were included. We examined factors associated with receipt of breast cancer treatment based on stage-specific guideline recommendations. Sociodemographic (e.g., age, region, and rurality), clinical (e.g., comorbidities), cancer-related (e.g., stage at diagnosis and nodal status) and health system (e.g., family interview with a physician) factors associated with overall treatment, surgical resection, mastectomy and radiation were explored using modified Poisson regression with robust standard error variance. Crude and adjusted risk ratios with 95% confidence intervals were estimated. RESULTS: The overall treatment cohort, surgical resection cohort, mastectomy cohort and radiation cohort included 365, 365, 333 and 138 females with IDD, respectively. Age, stage at diagnosis and lymph node status were significantly associated with overall breast cancer treatment. We identified that age, grade, lymph node status and radiation consult were significantly associated with surgical resection receipt. Among individuals who received surgery, those who were older, who had more advanced stages at diagnosis or who had a family interview were more likely to have mastectomy rather than breast-conserving surgery. Age and lymph node status were significantly associated with receipt of radiation. CONCLUSIONS: Sociodemographic, clinical, cancer-related and health system factors were associated with receipt of breast cancer treatment in a sample of breast cancer patients with IDD. Overall, these findings suggest that health system factors could contribute to disparities in treatment among individuals with IDD diagnosed with breast cancer.

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3. Ommensen B, Attwood T, Pachana NA, Sofronoff K. The potential for successful autistic ageing: Proposing a lifespan developmental psychology approach. Autism;2026 (Feb 22):13623613261418468.

Negative misconceptions about the inevitability of declining physical health and cognitive functioning in old age abound in society and in literature on autistic ageing. But there is a paradox of ageing: most older adults in the general population experience increases in life satisfaction and emotional wellbeing in later life that are associated with quality of life and indicative of successful ageing. Parallel patterns of later-life improvement in psychosocial functioning and emotional wellbeing have been found in attention deficit hyperactivity disorder and schizophrenia, which raises the tantalising question: could the paradox of ageing be true for older autistic adults too? Contemporary gerontological research that reconciles the contradictions inherent in this paradox from a lifespan developmental psychology perspective also informs global public health initiatives. These promote healthy successful ageing as a process of recovery, adaptation and growth in later life for people of all abilities. By contrast, there has been relatively little examination of autistic ageing from this perspective. Drawing on analyses of both gerontological and autism literature, this gap is addressed. Lifespan psychology’s potential relevance to the developmental trajectory of autism is explored, and an evidence-based theoretical framework to guide future autism research and clinical practice aimed at promoting successful autistic ageing is proposed.Lay AbstractWhat is already known about this topic?Despite experiencing physical and mental losses as they age, most older people are satisfied with life. They have more positive than negative emotions, and this is related to wellbeing and improved quality of life. According to lifespan psychology, this unexpected pattern is evidence of successful ageing. By contrast, the potential for successful ageing in autism is not well understood. Even though it informs the World Health Organization’s guidelines on healthy ageing, there has been relatively little consideration of lifespan psychology in relation to autistic ageing. The researchers’ aim was to address this gap.What does this article add?This article provides a novel approach to understanding and promoting successful autistic ageing. It describes lifespan psychology and associated models and theories and how they relate to autistic experience. It also explains how and why positive outcomes like quality of life and life satisfaction are realistic goals for older autistic adults.Implications for practice, research or policyLifespan psychology offers an evidence-based framework for guiding future research, policy and clinical practice to help older autistic adults achieve positive life outcomes, productivity, personal growth and wellbeing. Future research should test whether autistic older adults experience the same improvements in social and emotional wellbeing in later life as other groups in the population. This will help to make sure that health policy and clinical support are not based on negative assumptions about autistic ageing that do not reflect real-life experiences. Most importantly, this article shows that by thinking about ageing differently, there are opportunities for all autistic adults to enjoy healthy successful ageing.

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4. Quesnel K, Ellegood J, Lerch JP, Bérubé NG. Altered Brain Structure in an ATRX-Deficient Mouse Model of Autism Spectrum Disorder. Autism Res;2026 (Feb 22):e70205.

Mutations in the ATRX gene are a primary cause of alpha-thalassemia intellectual disability X-linked (ATRX) syndrome, which is characterized by intellectual disability, autism, and a range of brain structural abnormalities, including microcephaly. We previously showed that mice with conditional ATRX ablation in forebrain excitatory neurons display deficits in fear memory and autism-related behaviors, with some effects exhibiting sexual dimorphism. In this study, we used high-resolution magnetic resonance imaging (MRI) to systematically characterize brain structural changes associated with these behavioral abnormalities. Whole-brain analysis revealed male-specific microcephaly, while subregional analysis identified significant reductions in hippocampal structures and increased volume of the caudal cortex in mutant animals of both sexes. We also identified structural alterations in regions retaining ATRX expression, such as the thalamus, midbrain, cerebellum, and several fiber tracts. These findings suggest that ATRX loss disrupts the coordinated development of interconnected brain regions. Overall, our results implicate impaired cortico-thalamic-cerebellar connectivity as a potential neural substrate underlying the autistic-like behaviors observed in this mouse model, providing new insights into the neurobiological basis of ATR-X syndrome. Changes in a gene called ATRX are known to affect brain development and are linked to intellectual disability and autism. In our previous work, we found that removing this gene early in brain development caused mice to show behaviors like those seen in people with autism. In this study, we used detailed brain scans to see if these behavioral changes were linked to differences in brain structure. We found that male mice without ATRX had smaller brains and bodies, while female mice did not show the same brain size reduction. However, both male and female mice had smaller areas of the brain important for memory and movement, and larger areas involved in thinking and sensing. We also saw changes in parts of the brain where ATRX was still present, suggesting that early changes in one area can affect how the whole brain develops. These findings help us understand how early disruptions in brain development might lead to autism‐related behaviors. eng

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5. Ross LA, Molholm S, Foxe JJ. Associations between symptom severity in autism and functional neuroimaging measures of audiovisual speech perception. Neuroimage Clin;2026 (Feb 16);49:103971.

Individuals on the Autism Spectrum do not benefit as much from visual articulatory cues when compared to neurotypicals, especially under noisy environmental conditions. We hypothesized that this deficit would vary with the severity of Autism related symptoms and assessed this relationship in a behavioral speech-in-noise task (n = 32) and a functional neuroimaging study (n = 37). We found that Calibrated Symptom Severity Scores (CSS) were associated with poorer audiovisual performance but not performance in the auditory-alone condition indicating that impairments are limited to multisensory (MS) information processing. These findings underscore the validity of MS deficits and their potential relevance to the broader symptomatology in Autism. We also found that CSS significantly correlated with hemodynamic responses to audiovisual stimulation. Here, higher symptom severity was associated with lower multisensory gain in dorsal speech and language regions. Subsequent exploratory analysis suggested that individuals with Autism may not engage speech motor regions in similar ways to typically developing (TD) individuals.

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6. Sotelo-Orozco J, Taft DH, Al-Oboudi J, Baikie BC, Lake C, Miller M, Mills DA, Tancredi DJ, Schmidt RJ, Hertz-Picciotto I, Bennett DH. Mixed Evidence for Impact of Early Infant Gut Microbiome and Later Development of Autism Spectrum Disorder in the MARBLES Prospective Cohort Study. Autism Res;2026 (Feb 22):e70207.

This study investigated the relationship between early infant gut microbiome composition and subsequent neurodevelopmental outcomes. Fecal samples from children in the markers of autism risks in babies-learning early signs (MARBLES) study, a cohort with elevated likelihood of autism, were collected between 0 and 7 months of age and analyzed using 16S rRNA sequencing to evaluate whether the gut microbial composition during early infancy is associated with later neurodevelopmental diagnoses. Clinical classification as autism spectrum disorder (ASD), non-typically developing without ASD (non-TD), or typically developing (TD) was completed around 36 months of age using gold-standard assessment tools. Overall, no significant differences in alpha diversity or beta diversity, nor any differentially abundant bacterial taxa, were found between groups of infants who developed ASD or non-TD compared to those who went on to have TD. Nonetheless, our findings highlight some early differences in gut microbial composition during infancy that may relate to later neurodevelopmental outcomes. Before adjusting for multiple comparisons, infants who later developed ASD had slightly lower levels of Veillonella and Flavonifractor genera compared to children who were later found to be TD. These results suggest specific bacterial taxa may already differentiate in early infancy, but may be more subtle than other factors, such as mode of delivery and diet during early infancy. To understand longitudinal trajectories of the gut microbiome in association with later neurodevelopment, future studies should include a larger cohort to detect smaller effect sizes or investigate later time points in infancy. The human gut has many types of bacteria, some beneficial and some that may be harmful to health. Together these bacteria are referred to as the gut microbiome. Previous research shows that the bacteria in the human gut may differ in older children diagnosed with autism spectrum disorder compared to typically developing children. Children with autism are known to have problems with their gastrointestinal (GI) tract, though the relationship between GI health and autism is not well understood, particularly how the bacteria in the gut change in early life, before ASD behaviors begin to be seen. This study focuses on the gut microbiome in the first 7 months after birth and its relation to later development of autism, examined at 36 months of age. We found no major differences in the gut microbiome of infants who developed autism compared to those who did not. However, infants who later developed autism had slightly fewer of two bacteria types (Veillonella and Flavonifractor) early in life compared to infants who developed typically. However, these differences are minor compared to other factors, like whether the baby was born by C‐section or what they ate, which might matter more for the gut microbiome composition at this age than their later developmental diagnosis. eng

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7. Su X, Jin X, Sun B, Li X, Yi L. Peer rejection as a mediator between socio-emotional function and internalizing symptoms in autistic adolescents. Autism;2026 (Feb 22):13623613261421433.

Peer rejection is a distressing experience, which has been found to mediate the association between socio-emotional function and internalizing symptoms in neurotypical adolescents. To examine whether peer rejection statistically links socio-emotional function and internalizing symptoms in autistic adolescents, we measured their socio-emotional function (social skill, alexithymia, empathy), peer rejection, and internalizing symptoms. Autistic adolescents (N = 71), aged between 10 and 16 years (M = 12.73 years), completed questionnaires measuring peer rejection, socio-emotional function (alexithymia, empathy), and internalizing symptoms (depression, anxiety, social anxiety), and their parents completed the Autism-Spectrum Quotient questionnaire measuring adolescents’ social skills. Our results revealed that peer rejection was associated with internalizing symptoms, and peer rejection mediates the relationships between socio-emotional function (social skill, alexithymia, empathy) and internalizing symptoms. These findings underscore the importance of relational factors in the mental health of autistic adolescents and highlight the importance of addressing peer rejection through inclusive practices and social acceptance initiatives.Lay abstractTeenagers often find peer rejection distressing. It is also linked to mental health issues such as anxiety and depression. For autistic adolescents, experiencing peer rejection is even more common, but its associations with mental health are less understood. This study aimed to find out if peer rejection is related to anxiety and depression in autistic adolescents. We also wanted to see how social skills, emotional awareness (alexithymia), and empathy relate to peer rejection, and whether these associations extend to emotional distress (depression, anxiety, social anxiety). We surveyed autistic adolescents aged 10 to 16 about their social experiences, socio-emotional function, and emotional distress. Their parents provided social-skill information. Autistic adolescents who felt more rejected by their peers had higher levels of emotional distress. Moreover, teens who struggled more with social skills and emotional functions tended to feel more rejected by peers and to experience higher levels of emotional distress. Our findings suggest that relationships play a crucial role in the mental health of autistic adolescents. While building individual social and emotional skills is important, fostering supportive peer environments may also play a key role in promoting their well-being.

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8. Suleman S, Parmar P, Adams DK, Newbube C, Rajamohan S, John C, Juando-Prats C. Feasibility of a co-designed intervention to promote parental empowerment for children with developmental disabilities. Acad Pediatr;2026 (Feb 19):103255.

BACKGROUND: Caregivers of children with developmental disabilities, particularly those socially or economically marginalized, report high stress, decreased empowerment and difficulties navigating resources and programs. OBJECTIVE: This feasibility study co-designed and tested the demand, acceptability and implementation of a pilot intervention to increase social support, promote parental empowerment and increase access to care with families. METHODS: This study utilized principles of community based participatory research and human centered design. In partnership with two community organizations, a caregiver advisory council met for multiple co-creation sessions, and developed the pilot intervention. Participant attendance, pre- and post- surveys to measure satisfaction and knowledge uptake, and semi-structured interviews with participants were used to determine implementation, demand, and acceptability. RESULTS: 11 caregivers joined the advisory council and participated in 7 co-creation sessions. A three-pronged intervention was developed (Figure 2): a phone-based chat group; a toolkit and an accompanying workshop. 55 participants participated in the intervention at both partner sites. Parents and community service workers both reported feeling empowered to navigate services after participating in the workshop and utilizing the toolkit. The group chat was infrequently used but was felt to be a helpful tool to share additional resources and discuss specific topics. CONCLUSION: A three-part intervention co-developed with parents to improve access to services, increase social support and promote empowerment was implemented successfully, with high acceptability and demand. Our study demonstrates the critical importance of working alongside communities to co-create interventions to best serve the specific community needs.

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