Pubmed (TSA) du 27/10/26
1. Akçay S, Dinç Yavaş A, Poyrazoğlu HG, Cesar NS, Kaplan İ N, Uğur CC. Maternal Anxiety Symptoms, Sensory Processing, and Play Performance in Children Aged 4-6 Years with Autism Spectrum Disorder: A Cross-Sectional Study. Children (Basel). 2026; 13(10).
Background: Children with autism spectrum disorder (ASD) often show atypical sensory processing and reduced play participation, and their mothers frequently report elevated anxiety. However, maternal anxiety symptoms, sensory processing, and children’s play performance and playfulness have rarely been examined together, and the factors independently associated with maternal anxiety symptoms have not yet been clarified. Objective: This study examined relationships between maternal anxiety symptoms and children’s sensory processing, play performance, and playfulness in children with ASD aged 4-6 years, and identified factors independently associated with maternal anxiety symptoms. Method: In this cross-sectional study, 58 mother-child dyads were recruited from a special education center in Istanbul, Türkiye. Maternal anxiety was assessed with the Beck Anxiety Inventory, sensory processing with the Dunn Sensory Profile, and play with the Revised Knox Preschool Play Scale and Test of Playfulness. Results: Maternal anxiety was negatively correlated with play performance (ρ = -0.564, p < 0.001) and playfulness (ρ = -0.492, p < 0.001), and positively correlated with low registration and sensation-seeking raw scores (ρ = 0.474, p < 0.001 and ρ = 0.343, p = 0.008, respectively; higher raw scores indicate more typical, less atypical processing). Children with comorbid ADHD had mothers with higher anxiety and lower play scores. In a multivariable model (R(2) = 0.516), play performance (β = -0.411, p = 0.002) and, preliminarily, comorbid ADHD (β = 0.274, p = 0.027; only 10 children with ADHD) were independently associated with maternal anxiety; maternal education, employment, and school type were not. Conclusions: In young children with ASD, maternal anxiety symptoms were most strongly associated with the child's play performance, while a preliminary association with co-occurring ADHD requires confirmation in larger samples; these findings support considering maternal wellbeing in family-centered occupational therapy assessment.
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2. Allen S, Knott F, Branson A, Lane SJ. Daily Life Impacts and Desired Support for Mothers of Children with Sensory Integration Differences, with and Without Autism. Brain Sci. 2026; 16(10).
Background/Objectives: To address the needs of mothers of children with sensory integration differences, we need a greater understanding of their experience and what they find helpful. This study aimed to explore the impact of child sensory integration differences on daily activities and relationships and to identify the relationships, media, and parent interventions mothers regard as helpful and further support that is desired. It compared perceptions of mothers of autistic and non-autistic children. Methods: A single cohort descriptive observational survey study. Questions were generated from previous in-depth interviews. Results: Mothers of autistic children versus non-autistic children both with sensory integration differences reported greater impact on school and community activities and on some relationships. No differences were observed in factors mothers identified as helpful, such as media resources and relationships. Most mothers in the full cohort reported that child sensory integration differences had a pervasive impact on everyday activities and relationships for both mother and child. Supportive relationships, media, social media, and direct interventions to mothers were helpful. Mothers wanted more practical and emotional support for themselves, education of others, and specialist support for their child. Conclusions: Mothers of children with sensory integration differences identified social and professional relationships, media, and parent intervention as helpful, supporting a variety of intervention strategies.
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3. Alothman AA, Didden R, Ebrahim MT. The ARIEL Visual Search Task (AVST): Preliminary psychometric evaluation of a novel measure of selective visual attention in autistic adolescents. Res Dev Disabil. 2026; 178: 105407.
BACKGROUND: Selective visual attention is relevant to goal-directed behavior, yet visual-search measures vary in linguistic demands, stimulus construction, and methodological transparency. The aim of the current study was to develop the ARIEL Visual Search Task (AVST), a minimally linguistic performance-based measure of selective visual attention, and evaluate its feasibility, performance characteristics, reliability, convergent validity, and known-groups differentiation in autistic adolescents. METHODS: The AVST was developed using explicit rules for symbol construction, target-distractor similarity, form assembly, administration, and scoring. The study enrolled 40 autistic adolescents (mean age = 13.6 years, SD = 1.8) and 25 non-autistic adolescents (mean age = 13.4 years, SD = 1.7). Thirty-eight autistic participants completed Form A and contributed to the primary performance analyses. Data were analyzed to examine feasibility, score distributions, item and distractor performance, internal consistency, and known-groups differences. Sub-samples were used to examine test-retest reliability and convergent validity with the CEFT, while distractor classification was independently evaluated through expert review and a separate perceptual-evaluation sample. RESULTS: Thirty-eight autistic participants (95.0%) completed the AVST, with a mean completion time of 3.5 min (SD = 1.1). Mean Hits were 10.03 of 12 (SD = 1.8), and mean False Alarms were 4.3 (SD = 3.1). Item detection rates ranged from 65.8% to 94.7%, and internal consistency of the 12 target-detection items was KR-20 = .58. Preliminary test-retest ICCs ranged from.58 to.82, and AVST Hits and False Alarms showed modest associations with CEFT accuracy (ρ =.43 and -.38, respectively). Non-autistic participants showed higher Hits (|d| = 0.84, p < .001) and fewer False Alarms (|d| = 0.83, p = .001). Completion Time also differed moderately between groups (d = 0.60, p = .015), whereas the difference in Self-Corrections was smaller and not statistically significant (d = 0.43, p = .078). Distractor-related findings were broadly consistent with the predefined similarity framework. CONCLUSION: The AVST was feasible to administer in autistic adolescents and showed promising initial measurement properties, particularly for target detection, false selections, and completion time. These findings support further evaluation of the task's reliability and validity in larger and more diverse samples.
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4. Anderer S. Autism Incidence Has Remained Stable, Study Finds. Jama. 2026; 336(16): 1399.
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5. Ayyan M, Salameh H, Alladaboina S, Ayoub S, Subai A, Al Naimi H, Khan AS, Yousef M, Pal M, Chaari A. Environmental and genetic interactions in autism spectrum disorder: a literature review with a focus on air pollution. Environ Health. 2026; 25(1).
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is associated with complex interactions between genetic susceptibility and environmental exposures. More recently, air pollution has been investigated as a modifiable risk factor and contributor to the neurodevelopmental outcomes of the disorder. This review focuses on the Middle East and North Africa (MENA) region and discusses genetic, immunologic, and epigenetic findings that help explain how pollutants, including particulate matter (PM₂.₅, PM₁₀), nitrogen oxides, ozone, and dioxins, contribute to the pathogenesis of ASD and its specific involvement in neuronal pathways. Many pollutants have been found to increase oxidative stress, neuroinflammation, and endocrine disruption which alters DNA methylation and histone modification patterns. The pathology of this involves activation of the aryl hydrocarbon receptor (AhR) and its downstream CYP1A1/CYP1B1 pathways which link environmental to altered gene expression and neural circuits. Current studies have shown that prenatal and early postnatal exposures are critical windows in which air pollutants can impair synaptogenesis, microglial regulation, and neurotransmitter balance. Significantly, sex-specific differences further modulate susceptibility, with males demonstrating heightened vulnerability due to hormonal and immune interactions. While progress has been made in uncovering these mechanisms, challenge in establishing causality and addressing diagnostic biases persists. Future directions should integrate longitudinal cohorts, omics-based biomarkers, and machine-learning models to clarify exposure-response relationships and guide personalized prevention strategies. Understanding how environmental and genetic factors converge to disrupt neurodevelopment is essential to mitigating ASD risk in increasingly polluted environments.
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6. Beyer N, Volk T, Luksch H, Ring M, Vetter NC, Roesen-Wolff A, Lee-Kirsch MA, Roessner V. Altered cytokine profiles and elevated lactate levels in children with autism spectrum disorder: indications of a dysregulated immune-metabolic network?. Front Psychiatry. 2026; 17: 1904470.
INTRODUCTION: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition characterized by difficulties in social communication and restricted, repetitive behavior. The etiology and pathophysiology of ASD remain largely unknown; however, a complex interplay of genetic and environmental factors is widely assumed. More recently, altered cytokine/chemokine profiles and a potential vulnerability to mitochondrial alterations have been proposed. METHODS: We measured blood lactate and pyruvate and quantified a cytokine/chemokine panel including IL-1β, IL-2, IL-6, TNF-α, IL-8, IFN-β, RANTES, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, CCL11/Eotaxin-1 and CXCL10/IP-10 in a group of autistic children in comparison to a non-autistic age-, gender- and IQ-matched control group. RESULTS: We observed elevated lactate levels, lower concentrations of IL-1β and TNF-α in autistic- compared with control children. In addition, lactate, MIP-1β/CCL4 and TNF-α was significantly associated with behavioral measures of autistic behavior. Pyruvate, the lactate/pyruvate ratio and all other analytes did not differ between groups. DISCUSSION: We conclude that the observed cytokine/chemokine profile may reflect a dysregulated immunological network in autistic children. Elevated lactate may point to metabolic abnormalities with possible mitochondrial involvement. However, unchanged pyruvate and lactate/pyruvate ratio do not support overt mitochondrial dysfunction. These findings require replication in larger studies.
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7. Bjørklund G, Crăciun EC, Dronca E. Whole-blood lead-copper association in children with autism spectrum disorder: Implications for toxic-essential metal interactions. Metab Brain Dis. 2026; 41(1).
Lead (Pb) is a developmental neurotoxicant that can interfere with essential-metal regulation, whereas copper (Cu) is a tightly regulated redox-active trace element required for normal neurological function. This study investigated whether whole-blood Pb concentrations were associated with whole-blood Cu concentrations in 28 children with autism spectrum disorder (ASD), compared with 28 pediatric controls closely matched for age and with the same sex distribution. Mean whole-blood Pb concentration was 70.29 ± 31.34 µg/L in the ASD group and 47.99 ± 13.95 µg/L in controls. Pb concentrations were higher in ASD (geometric mean ratio 1.394, 95% confidence interval [CI] 1.146-1.697, p = 0.001). Within the ASD group, Pb was positively associated with Cu (Pearson r = 0.385, 95% CI 0.014-0.663, p = 0.043), with a regression slope of 1.940 µg/L Cu per 1 µg/L Pb (95% CI 0.067-3.813; R² = 0.148). After adjustment for age and sex, the Pb coefficient remained similar in magnitude (β = 1.765, 95% CI - 0.174 to 3.704, p = 0.072). The Pb-Cu correlation was not significant in controls, and there was no evidence that the Pb-Cu association differed between the ASD and control groups. The association remained directionally consistent across additional sensitivity analyses, and adjustment for Childhood Autism Rating Scale (CARS) score did not materially alter the Pb coefficient. The findings are compatible with experimental evidence on Pb-Cu interactions and Cu homeostasis but do not establish causality or ASD-specific Pb-Cu coupling. Replication in larger, prospectively characterized cohorts is required.
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8. Brilhante AVM, Brasil CCP, da Silva RM, Mota L, Sabóia L, de Amorim MMR. ‘I Just Wanted It to End’: Sensory Experiences of Autistic Women During Pregnancy and Childbirth. Autism. 2026: 13623613261495469.
Autistic women experience the perinatal cycle with specific sensory challenges that remain insufficiently documented, particularly among those with diverse support levels. This qualitative study investigated sensory processing experiences of autistic women during pregnancy and labour, and how environmental and attitudinal factors articulate with sensory overload. Thirty-four autistic Brazilian women with Support Levels 1 and 2 (Diagnostic and Statistical Manual of Mental Disorders [5th ed., text rev.]) participated in four Hermeneutic-Dialectic Circle (HDC) cycles through semi-structured interviews in multiple formats. Iterative hermeneutic-dialectic analysis, supported by NVivo, identified four themes: (1) Pregnancy as a sensory amplifier; (2) The birth environment as the epicentre of sensory overload; (3) Communication barriers and professional invalidation; and (4) Sensory experiences in early motherhood. Pregnancy amplified pre-existing sensitivities, particularly olfactory and proprioceptive. The hospital environment emerged as the epicentre of overload, with touch as the most aversive stimulus. Peritraumatic dissociation was reported by 19 participants (56%). The deliberate inclusion of women with intellectual disability and complex communication needs revealed that saturation observed in earlier cycles was artifactual, a finding with methodological implications for qualitative autism research.Lay AbstractAutistic women often face challenges during pregnancy, childbirth and the postpartum period related to how they process sensory information such as sounds, lights, touch and smells. Very little research has explored how these differences affect the experience of becoming a mother, and even less has included autistic women with higher support needs or complex communication needs. This study explored the sensory experiences of 34 autistic women in Brazil through in-depth interviews, deliberately including women with Support Levels 1 and 2, some of whom used augmentative and alternative communication. The interviews were conducted in multiple formats (video call, in-person and text messaging) to ensure accessibility. We found that pregnancy amplified pre-existing sensory sensitivities. Smells, temperature changes and foetal movement were experienced with an intensity far beyond what is typically reported, sometimes causing shutdowns and crises. The hospital birth environment was a major source of sensory overload, with touch being the most distressing stimulus: 31 of 34 women reported aversive experiences related to being touched during labour. Even comfort techniques widely recommended for pain relief, such as massage, were described as unbearable. Communication barriers intensified suffering throughout the perinatal cycle: women reported that health care professionals frequently dismissed their sensory experiences as exaggeration or anxiety, which made it harder to access appropriate care. More than half the participants (19 of 34) reported memory gaps and dissociation during labour, suggesting that childbirth can be a traumatic event for autistic women when care is not adapted to their sensory needs. When health care teams made accommodations (reducing lighting, minimising unnecessary touch, maintaining continuity of care, providing predictability), women reported substantially better experiences. A key methodological finding was that the apparent saturation of themes observed when only women with Support Level 1 were interviewed proved artifactual: including women with higher support needs revealed new and important experiences that would otherwise have been missed. These findings highlight the need for sensory-informed, neurodiversity-affirming perinatal care and for research that deliberately includes autistic women with diverse support levels and communication profiles.
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9. Camussi D, Marchese M, Ogi A, Fronte B, Nicoletti F, Santorelli FM, Mero S. Effects of β-Glucans on Pro-Inflammatory Markers and Behavioral Phenotype in a Valproic Acid (VPA)-Induced Autism Model in Zebrafish. Int J Mol Sci. 2026; 27(20).
Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition in which neuroinflammation, oxidative stress, and synaptic dysfunction act as converging mechanisms. Prenatal exposure to valproic acid (VPA), an antiepileptic drug and histone deacetylase inhibitor, is a recognized environmental risk factor associated with ASD-like phenotypes. Zebrafish, with conserved neuroimmune pathways, rapid development, and quantifiable social behavior, represents a robust model for investigating ASD pathophysiology and testing therapeutic candidates. This study aimed to assess if a previously selected concentration of VPA is capable of inducing persistent alterations from early development through adulthood, and to assess the potential of β-glucans, natural polysaccharides with antioxidant and immunomodulatory properties, to mitigate VPA-induced alterations. A multimodal approach included morphological evaluation, mitochondrial respiration, quantitative PCR of inflammatory markers, and behavioral assays targeting locomotion, anxiety-like responses, and social preference. Low-dose VPA (25 μM) induced developmental and behavioral difficulties, accompanied by a transient reduction in mitochondrial respiratory capacity. β-glucan supplementation attenuated selected VPA-induced alterations, including inflammatory gene-expression changes in larvae and behavioral alterations in adulthood. Overall, these findings provide preclinical evidence that β-glucans can modulate selected VPA-induced inflammatory, molecular and behavioral alterations and support further investigation of their potential effects in neurodevelopmental models.
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10. Carroll A, Adams D, Simpson K. Autistic Student Well-Being Indicators at School: Parent, Educator, and Therapist Perspectives. J Autism Dev Disord. 2026.
PURPOSE: Autistic students experience high distress and unmet support needs at school, yet there is limited school‑based evidence to guide how their well‑being is understood in everyday educational contexts. This study aimed to address this gap by examining school‑based indicators of autistic student well‑being across multiple dimensions. METHODS: A two‑phase, multi‑informant design was used. In Phase 1, qualitative data were collected from caregivers, educators, and school‑based therapists (n = 41) to identify externally observable indicators of high and low well‑being. In Phase 2, a separate sample (n = 36) evaluated the perceived reliability of the most frequently identified indicators by participants in Phase 1. RESULTS: Inductive content analysis identified 94 indicators of high well‑being and 99 indicators of low well‑being. Three key findings emerged. First, indicators varied substantially in how they were expressed across students, highlighting the importance of interpreting change relative to individual baselines rather than normative expectations. Second, many indicators reflected specific dimensions of well‑being and did not function as global markers across contexts. Third, indicators most frequently reported were not always those judged to be most reliable, underscoring limitations of frequency‑based approaches. CONCLUSION: These findings demonstrate that autistic student well‑being at school is multidimensional, context‑dependent, and individually patterned. By clarifying how well‑being indicators are identified and interpreted in school settings, this study provides a foundation for future practice‑focused tools, professional learning, and research that supports more responsive and inclusive approaches for autistic students.
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11. Fang Y, Dou Z, Liu Y, Zong Y, Wang S, Li S, He N, Li N. Metabolic Dysregulation and Metabolite-Targeted Interventions in Autism Spectrum Disorder: Mechanisms and Translational Perspectives. Metabolites. 2026; 16(10).
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder marked by impaired social communication and restricted repetitive behaviors. Metabolic dysregulation is increasingly recognized as a key intermediate mechanism linking genetic and environmental factors to abnormal neurodevelopment in ASD. This review summarizes ASD-related metabolic abnormalities involving gut microbial metabolites, energy metabolism, neurotransmitter pathways, and immune-metabolic crosstalk. Such metabolic disturbances affect neurodevelopment via immune activation, oxidative stress, mitochondrial dysfunction, and disrupted neurotransmitter homeostasis, ultimately impairing synaptic plasticity and neural connectivity. We also outline the preclinical and clinical progress of metabolite-targeted interventions, which show potential to modulate relevant metabolic pathways. However, it should be noted that improvements in specific metabolic biomarkers may only be associated with, rather than definitively drive, behavioral changes. However, current studies are constrained by inconsistent trial designs, small cohorts, and inadequate mechanistic verification; furthermore, interindividual metabolic heterogeneity limits universal intervention efficacy. We discuss clinical translation barriers and propose future priorities: defining metabolic subtypes, validating biomarkers, and developing precision metabolic interventions. Elucidating these metabolic mechanisms will advance targeted, personalized therapies to improve neurodevelopmental outcomes in ASD.
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12. Flaherty E. Mapping the Distribution of Autism From the Census of Northern Ireland, 2021. Autism. 2026: 13623613261496337.
This piece examines the data and preliminary geographical patterns yielded from a question on autism included in the Census of Northern Ireland in 2021. There are two objectives here: (a) to present summary statistics, indicators of spatial clustering, and assess the correlation of autism with other census-based socioeconomic indicators, and (b) to assess the opportunities and limitations offered by this dataset in light of international work on the spatial distribution of autism. This exercise reveals evidence of spatial clustering and patterning, particularly within urban areas (the City of Belfast especially), and strong differences between urban Belfast and the Rest of Northern Ireland. Explorations of socioeconomic correlates of autism show an association between autism and family structure, education and labour market status.Lay AbstractA Geography of Autism? Preliminary Findings From the Northern Ireland Census, 2021There is a lot of research coming out about Autism and neurodiversity. Part of that research includes studies using maps and other tools from geography. These maps allow us to look at where Autism rates might be high or low, and to see if there are any patterns. Do places with high or low rates of Autism cluster together? Are places with high Autism rates closer to places where people or families who suspect neurodivergence might go to get an assessment? Once we know this, we can then start to look at other features of places, like the percentage of people unemployed, living in poverty, lone parent families or levels of education. This lets us figure out whether certain features are correlated with Autism. Are areas with higher percentages of lone parent families more likely to also have high Autism rates? This is important because past studies might have looked at environmental influences in Autism such as whether an area was near a busy motorway or a source of environmental contamination. I am interested in what a region like Northern Ireland can tell us about why certain areas might have higher rates of Autism. This will let us figure out more about how detection works, where services might be needed and how information on neurodivergence might spread within certain types of community more so than others.
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13. Gargus JJ. From Signal to Memory: A Proposed Adaptive Hierarchy Linking Autism-Associated Genes to Sensory Homeostasis. Genes (Basel). 2026; 17(10).
Every nervous system must preserve sensitivity to change while reducing responses to constancy. This review defines that adaptive objective as sensory homeostasis: the process through which familiar information recedes while unexpected or biologically important events remain salient. Its disruption is particularly relevant to autism spectrum disorder (ASD), in which sensory abnormalities occur across multiple modalities. Large-scale sequencing studies have identified hundreds of ASD-associated genes spanning neuronal excitability, synaptic function, intracellular signaling, transcription, and chromatin regulation. This hypothesis-driven narrative review asks whether the established functions of independently identified ASD-associated genes support a directional framework through which genetic vulnerability could compromise sensory homeostasis. Beginning with a prespecified Autism Sequencing Consortium-derived set of 185 ASD-associated genes, and separately classifying complementary genetic and mechanistic evidence, the review organizes a bounded subset into three functional levels: generation and spatial organization of intracellular Ca(2+) signals; interpretation of those signals by electrical, biochemical, synaptic, and transcriptional decoders; and stabilization of selected responses through transcriptional and chromatin-regulatory mechanisms that establish adaptive cellular memory. The resulting 44-gene core contains 32 of the 185 members distributed across all three levels and identifies IP(3)R-mediated endoplasmic-reticulum Ca(2+) release as an important, but not exclusive, Level 1 convergence mechanism in signal generation. The proposed framework predicts distinct proximal defects that converge on abnormal response trajectories across repeated stimulation, providing a testable connection among ASD genetics, adaptive cellular memory, and sensory phenotype.
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14. Garotti R, Aiello S, Riccio MP, Pezone M, Fiorile AMF, Marani N, Bravaccio C, Terrone G. Impact of Epileptiform Abnormalities on Functional Phenotype in a Cohort of Autism Spectrum Disorder Patients With or Without Epilepsy: A Monocentric Retrospective Study. J Autism Dev Disord. 2026.
PURPOSE: Autism Spectrum Disorder (ASD) and epilepsy frequently co-occur, suggesting shared neurobiological underpinnings. While no specific seizure type or epilepsy syndrome is consistently associated with ASD, Epileptiform Abnormalities (EAs) are commonly observed in affected individuals, though their clinical significance remains unclear. METHODS: This study examined the impact of EAs and epilepsy on the functional phenotype of 338 individuals with ASD, assessed through video-EEG (v-EEG) and standardized psychometric tools (ADOS-2, Leiter-R, WISC-IV, VABS). RESULTS: Results showed that ASD individuals with epilepsy exhibited significantly lower cognitive performance compared to those with ASD alone or with EAs. Additionally, greater symptom severity was observed in the ASD-+EA group. However, no significant differences emerged in adaptive functioning or language abilities. CONCLUSION: These findings highlight the potential influence of epileptiform activity on cognitive and behavioral outcomes in ASD. Further longitudinal research is warranted to elucidate the prognostic implications of EAs in ASD and better characterize its impact on functional profile.
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15. Güeita-Rodríguez J, Ogonowska-Slodownik A. From Sensory Regulation to Participation: A Clinical Reasoning Framework for Aquatic Therapy in Children with Autism Spectrum Disorder. Children (Basel). 2026; 13(10).
BACKGROUND AND OBJECTIVE: Research on aquatic interventions for children with autism spectrum disorder (ASD) has spanned over four decades, yet the field remains characterized by a fragmented evidence where therapeutic techniques often coexist without a unifying conceptual logic. This has led to a translational gap between research findings and clinical decision-making. This narrative review aimed to synthesize four decades of research into an evidence-informed clinical reasoning framework to capture the evolution of aquatic therapeutic practice and support clinical decision-making. METHODS: Literature search was conducted in PubMed, Scopus, and Web of Science, covering publications from the earliest available records to May 2026. Studies were analysed according to their therapeutic concepts, clinical reasoning logic, and outcome domains. RESULTS: A total of 30 studies met the inclusion criteria and were included in this review. The resulting synthesis enabled the derivation of an evidence-informed clinical reasoning framework representing five dominant therapeutic perspectives that characterize the development of aquatic clinical reasoning across the literature. By synthesizing peer-reviewed literature, we identified five dominant clinical reasoning paradigms that emerged across the development of the literature and continue to inform contemporary aquatic practice: (1) Exploratory and Sensory-Regulatory, (2) Skill- and Safety-Oriented, (3) Structured and Functional, (4) Participation- and Social-Oriented, and (5) Individualized and Outcome-Informed Practice. CONCLUSIONS: This conceptual roadmap may help clinicians align aquatic intervention strategies with individual therapeutic priorities, functional goals, and participation needs. The proposed framework provides a bridge between historical practice and contemporary evidence, supporting individualized and outcome-informed clinical reasoning in aquatic therapy for children with ASD. The five phases should be interpreted as dominant paradigms of clinical reasoning that may coexist within practice rather than as mutually exclusive or strictly chronological categories.
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16. Guo S, Liu F, Yang S, Huo R. A Dynamic and Recursive Process of Resilience in Chinese Families of Children with Autism Spectrum Disorder: A Qualitative Study. Behav Sci (Basel). 2026; 16(10).
OBJECTIVE: This study examines how Chinese families of children with autism spectrum disorder (ASD) developed family resilience across their caregiving experiences and identifies the conditions that shape these processes. METHODS: In-depth retrospective interviews were conducted with 15 parents and 4 staff members of an ASD service organization in Dalian, China. Reflexive Thematic Analysis was used, with Walsh’s family resilience framework serving as a sensitizing lens. Staff perspectives were treated as supplementary contextual accounts. RESULTS: Three recurring patterns were identified across families, including crisis-oriented disruption and uncertainty after diagnosis, active exploration and family reconstruction during intensive caregiving, and relative stabilization and expanded adaptation as routines and supports settled. These patterns were revisited and combined in different orders rather than following a fixed linear sequence. Resilience was shaped by a mix of intrafamilial and broader contextual conditions. Intrafamilial conditions included intergenerational caregiving and marital relationship. Contextual conditions included cultural norms, stigma, service access, and social support. Parental education was associated with adaptation but was not independent of income and service access. CONCLUSIONS: Family resilience in Chinese families of children with ASD should be understood as a dynamic, recursive, and contextually embedded process. The findings point to the need for family-centered, stigma-sensitive interventions that support the wider family and respond to families’ shifting needs over time.
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17. Hinderliter RJ, Bloom SE, Devine ER, Spencer CN. An Investigation into the Efficacy of Self-Monitoring in the Context of Mixed Schedules for Reducing Stereotypy in Children with Autism Spectrum Disorders. Behav Sci (Basel). 2026; 16(10).
Children with Autism Spectrum Disorder (ASD) may engage in stereotypy (STPY). STPY may be problematic if it interferes with other activities or is self-injurious. We used self-monitoring (SM) alone and in a two-component mixed schedule to reduce stereotypy in three boys with ASD. We used a multiple baseline across participants design with an embedded reversal for one participant. After confirming an automatic function for STPY, baseline was followed by three conditions: Differential Reinforcement (Accuracy), during which the participant received reinforcement for accurately recording STPY; Differential Reinforcement of Other Behavior (DRO) with SM, during which the participant received reinforcement for not engaging in STPY; and a two-component mixed-schedule condition in which the reinforcement contingency (either differential reinforcement for accuracy or the absence of STPY) was unsignaled. Training SM reduced STPY in two participants. However, the third participant’s STPY only reduced with DRO. For him, a two-component mixed schedule in which the reinforcement contingency was unsignaled, reduced STPY, thus reducing the observation requirement for DRO. Thus, using indiscriminable contingencies may contribute to more efficient SM interventions, when reducing STPY is a goal identified by the participant themselves and is considered socially valid.
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18. Hiralal KR, Bouw N, Diederen LD, Lubbers K, Dierckx B, Greaves-Lord K, Hillegers MHJ, Dieleman GC, Mous SE. Response inhibition in children and adolescents with fragile X syndrome. Child Neuropsychol. 2026: 1-21.
Limited knowledge exists on the high degree of overlap, such as in executive functioning, between fragile X syndrome (FXS) and autism. We aimed to better understand the shared response inhibition difficulties and the underlying neurocognitive mechanisms in individuals with FXS and autism. Children and adolescents with (1) FXS (n = 29), (2) a positive autism screening (hereafter: autism group) (n = 28), or (3) neurotypical development (n = 25) were recruited. To assess response inhibition abilities, we used a go/no-go task and the auditory attention + response set inhibition subtask of the NEPSY-II. To compare the amount of cognitive effort that is elicited during response inhibition, we investigated the pupil response during the go/no-go task. Children and adolescents with FXS showed more difficulties with inhibiting responses compared to the autism and neurotypical groups across the different response inhibition tasks. The autism and neurotypical groups did not differ in performance on the tasks. Pupillometric analysis showed subtle, but significant differences in pupil size between the FXS and both other groups. The autism and neurotypical groups did not differ in pupil size. Children and adolescents with FXS have difficulties with inhibiting their responses compared to the neurotypical and autism group, even when a task is relatively simple. This may reflect reduced cognitive effort in FXS, as indicated by reduced pupil dilation. Future research should explore other executive functions in FXS at behavioral and physiological measurement levels, to identify neurocognitive mechanisms across domains.
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19. Hurtado Ruíz MG, Arranz Calderón MJ, Pérez Solá V, Prades Oropesa M, Hervás Zúñiga A. Association of Motor Stereotypies with Emotional Dysregulation and Anxiety/Depression Symptoms in Children with Autism Spectrum Disorder. Children (Basel). 2026; 13(10).
Background: Comorbidities such as anxiety and challenging behaviours are common in children with autism spectrum disorder (ASD). These comorbidities are often linked to emotional dysregulation (ED) and are frequently accompanied by motor stereotypies (MS). Objective: This study aimed primarily to examine the association between lifetime motor stereotypies (LMS) and both emotional dysregulation (ED) and anxiety/depression symptoms (ADS) in children with ASD. Additionally, a secondary objective was to explore the association between ED and the lifetime broader spectrum of restricted and repetitive behaviours (RRBs), and their specific subtypes. Methods: The study included 151 children with ASD (ages 3-11). ADS and ED were assessed using the Child Behaviour Checklist (CBCL) and the Child Behaviour Dysregulation Profile (CBCL-DP), respectively, while LMS and lifetime RRBs were evaluated via the Autism Diagnostic Interview-Revised (ADI-R). Data were analyzed using regression models. Results: Frequent LMS were significantly associated with ED and ADS. Gender, intellectual disability (ID), and ASD severity did not significantly influence these relationships. Age had a significant effect on the association between frequent LMS and ADS. No significant correspondence was found between ED and lifetime RRBs in general or with subtypes of RRBs. Conclusions: Our findings suggest that frequent LMS are associated with ED and ADS in children with ASD. Identifying ASD subgroups based on the presence of LMS may contribute to the development of detection methods and targeted and effective interventions for ED. Differences observed between LMS and other RRBs in relation to ED support the notion that low- and high-level repetitive behaviours involve distinct clinical features and should be studied independently.
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20. Kalandadze T, Gabunia M, Javakhishvili N, Kobuladze T, Tchintcharauli T. Correction: Perspectives of Autistic People, Parents, and Healthcare Professionals on Communication in Healthcare Settings and Related Needs in Georgia: A Qualitative Study. J Autism Dev Disord. 2026.
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21. Karras SN, Goulis DG, Dalamaga M, Kypraiou M, Vlastos A, Anemoulis M, Harizopoulou V, Mastorakos G, Skoutas D, Polyzos SA, Goulas A. Cord Blood 3-Epi-25-Hydroxyvitamin D(3) and Autism-Related Cognitive Traits at Age 10 Years: An Exploratory Secondary Analysis of the KLOTHO Birth Cohort. Nutrients. 2026; 18(20).
BACKGROUND: The C3 epimer of 25-hydroxyvitamin D(3) [3-epi-25(OH)D(3)] can be measured in maternal and umbilical cord circulation, but whether it is related to later neurodevelopment is unknown. OBJECTIVE: To explore associations between cord 3-epi-25(OH)D(3) and parent-reported autism-related trait domains at 10 years in the KLOTHO birth cohort. METHODS: This secondary analysis used prospectively collected perinatal samples and 10-year questionnaire data. Vitamin D metabolites were quantified by liquid chromatography-tandem mass spectrometry with epimer separation. The Australian Scale for Asperger’s Syndrome was used dimensionally, not diagnostically. Spearman correlations, false-discovery-rate (FDR) correction across 13 unique bivariate comparisons, supportive linear regressions, sex-stratified analyses, and a stricter record-linkage sensitivity analysis were conducted. RESULTS: Data were available for 87 offspring (41 boys and 46 girls). Cord 3-epi-25(OH)D(3) was inversely associated with cognitive-domain score (Spearman ρ = -0.412; p < 0.001; Benjamini-Hochberg q = 0.001). The crude regression estimate was also inverse (B = -0.285; 95% CI, -0.458 to -0.112; p = 0.002), but the association attenuated after covariate adjustment and all adjusted confidence intervals included the null. A stricter linkage analysis remained significant (n = 84; ρ = -0.350; p = 0.001). The correlation was numerically stronger in boys than girls, but the between-sex comparison was not significant (p = 0.075). A positive correlation was also observed for social and emotional traits (ρ = 0.302; q = 0.023), indicating inconsistent directions across domains; the tertile analysis was non-significant. CONCLUSIONS: Cord 3-epi-25(OH)D(3) was associated with lower cognitive-domain scores in unadjusted rank analyses, but the lack of stable adjusted linear evidence, inconsistent domain pattern, and small sample restrict interpretation. These findings are hypothesis-generating and do not imply causality, sex-specific effects, or clinical utility.
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22. Kartal F, Teksin G, Yarız K, Öztürk HM. Psychological Pain and Its Associations with Autistic Traits, Anger Rumination, and Tolerance for Mental Pain Among Medical Students. Behav Sci (Basel). 2026; 16(10).
This study aimed to examine the relationships among autistic traits, psychological pain, anger rumination, and tolerance for psychological pain in medical students. This single-center, cross-sectional study included 544 medical students at Kırıkkale University Faculty of Medicine, Türkiye (mean age: 22.40 ± 1.91 years; 55.3% women). Participants completed the Autism Spectrum Quotient (AQ), Orbach and Mikulincer Mental Pain Scale-8 (OMMP-8), Tolerance for Mental Pain Scale-10 (TMPS-10), and Anger Rumination Scale (ARS). Higher autistic traits were associated with greater psychological pain and anger rumination and lower tolerance for psychological pain. Students with AQ scores ≥26 had significantly higher psychological pain and anger rumination and lower tolerance for psychological pain than those with AQ scores <26. In multivariable analysis, autistic traits, anger rumination, and tolerance for psychological pain were independently associated with psychological pain. Cross-sectional indirect-effect analyses showed significant indirect effects through anger rumination (b = 0.112, 95% CI [0.066, 0.162]) and tolerance for psychological pain (b = 0.185, 95% CI [0.127, 0.243]), while the corresponding direct effects remained significant. These findings highlight the relationships among autistic traits, anger rumination, tolerance for psychological pain, and psychological pain in medical students.
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23. Königstein D, Kisko TM, Michels S, Alferink J, Wöhr M, Culmsee C, Kockskämper J. Dual Role of CACNA1C/Ca(V)1.2 in Cardiac and Neuropsychiatric Disease. Biomolecules. 2026; 16(10).
The CACNA1C gene encodes the α(1C) subunit of voltage-gated Ca(V)1.2 calcium channels, serving many pivotal functions throughout the body, including in the heart and brain. Clinical and genetic evidence implicates altered expression and/or function of CACNA1C/Ca(V)1.2 in both cardiac and neuropsychiatric disease, including hypertension, cardiac arrhythmias, coronary artery disease, schizophrenia, bipolar disorder, depression, and autism. Gain-of-function mutations in CACNA1C cause Timothy syndrome, a potentially lethal multi-organ disorder with severe cardiac and neuropsychiatric defects. Conversely, the complete loss of Cacna1c is lethal in mice. The development of viable mouse and rat models with Cacna1c haploinsufficiency has allowed us to study the consequences of reduced expression and function of Cacna1c/Ca(V)1.2 for heart and brain function from the molecular and cellular to the behavioral level. We review recent findings from these rodent models, revealing (i) alterations in behavior and (ii) in neuronal and non-neuronal function, as well as (iii) an impaired ability of the heart and its cardiomyocytes to adapt to (sympathetic) stress. Results lend further support to the notion that CACNA1C/Ca(V)1.2 dysfunction represents a common link between cardiac and neuropsychiatric disorders and that appropriately targeting CACNA1C/Ca(V)1.2 in selected patients may hold the promise of treating both conditions effectively with a single drug.
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24. Kurtulmuş A, Ereğli B, Nas Dönmez B, Görmez A. Circulating Soluble Urokinase Plasminogen Activator Receptor and C-Reactive Protein Concentrations in Adults with High-Functioning Autism. Brain Sci. 2026; 16(10).
Background: Immune dysregulation has been implicated in the pathophysiology of autism spectrum disorder (ASD). Soluble urokinase plasminogen activator receptor (suPAR) is a stable biomarker of chronic immune activation that has not previously been investigated in ASD. We compared circulating suPAR and C-reactive protein (CRP) concentrations in adults with high-functioning ASD and healthy controls. Methods: In this cross-sectional case-control study, 38 adults with high-functioning ASD and 37 healthy controls were included. Plasma suPAR and CRP concentrations were measured using enzyme-linked immunosorbent assays. Group differences were examined using hierarchical multiple linear regression analyses adjusting for age, sex, body mass index (BMI), and current smoking status. The Autism Spectrum Quotient (AQ) was administered to all participants, and associations between inflammatory biomarkers and autistic traits were assessed using Spearman’s rank correlation analyses. Sensitivity analyses were performed after excluding participants with CRP concentrations > 10 mg/L to minimise the potential influence of acute inflammatory conditions. Results: In unadjusted analyses, CRP concentrations were significantly higher in the ASD group (p = 0.006), whereas suPAR concentrations did not differ (p = 0.163). After adjustment for age, sex, BMI, and smoking status, the association between ASD and CRP was no longer significant (p = 0.181), with BMI emerging as the strongest independent predictor of CRP (p < 0.001). No association was observed between ASD and circulating suPAR concentrations in either unadjusted or adjusted analyses (p = 0.612). CRP, but not suPAR, was positively correlated with AQ total scores (p = 0.026). Sensitivity analyses excluding participants with high CRP concentrations yielded findings consistent with the primary analyses. Conclusions: Adults with high-functioning ASD showed no evidence of elevated circulating suPAR concentrations. The attenuation of CRP group differences after adjustment for BMI and smoking status highlights the importance of accounting for metabolic factors when interpreting peripheral inflammatory biomarkers in ASD. These findings do not support elevated suPAR levels in adults with high-functioning ASD.
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25. Lipiński P, Górska S, Brąszkiewicz J, Rydzanicz M, Płoski R. Asparagine Synthetase Deficiency: A Novel ASNS Variant and a Systematic Review of Clinical Phenotypes and Cerebrospinal Fluid Asparagine Levels. Biomolecules. 2026; 16(10).
BACKGROUND: Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder associated with microcephaly, severe developmental impairment, epilepsy, and progressive cerebral atrophy. Reduced cerebrospinal fluid (CSF) asparagine has been proposed as a supportive biochemical marker, but the extent to which it provides useful diagnostic information remains uncertain. METHODS: We report a female patient with molecularly confirmed ASNSD and conduct a systematic review of molecularly confirmed cases in accordance with PRISMA 2020. PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched from inception to 20 September 2026. Clinical, survival, neuroimaging, molecular, and CSF-asparagine data were extracted for individual patients whenever available. Outcome frequencies were calculated only among patients for whom the relevant feature was reported. RESULTS: The patient developed infantile spasms at 5 months of age after an initially unremarkable brain MRI and subsequently showed drug-resistant epilepsy, profound developmental impairment, progressive microcephaly, spastic tetraparesis, feeding difficulties, and severe cortical and subcortical atrophy. Exome sequencing identified compound-heterozygous ASNS variants: the novel early frameshift variant c.81_82del (p.Gly28SerfsTer7) and the previously reported c.97C>T (p.Arg33Cys), confirmed in trans. The systematic review included 106 published molecularly confirmed patients. Developmental impairment was reported in 101/101 assessable patients, microcephaly in 99/106, epilepsy in 72/86, and at least 48 deaths were documented. Exact individual CSF asparagine concentrations were available for only six patients; five were reduced or undetectable and one was within the local reference interval. CONCLUSIONS: The novel c.81_82del variant expands the molecular spectrum of ASNSD. The available evidence does not permit calculation of a validated diagnostic threshold, sensitivity, specificity, or predictive values for CSF asparagine. A reduced concentration may support the diagnosis, whereas a normal concentration does not exclude ASNSD. Molecular testing remains the diagnostic standard and should be considered early in patients with developmental and epileptic encephalopathy, progressive microcephaly, and cerebral atrophy, even when early MRI or routine metabolic investigations are unrevealing.
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26. Lu M, Zou Q, Duan T, Zhao J, He H. Network analysis of anxiety and related factors in preschool children with autism spectrum disorder. Res Dev Disabil. 2026; 178: 105412.
PURPOSE: Anxiety is a common comorbid condition in children with autism spectrum disorder (ASD), with a significantly higher prevalence than in neurotypical children, and is associated with adverse developmental outcomes. Previous research has linked intolerance of uncertainty (IU), sensory over-responsivity (SOR), and restricted and repetitive behaviors (RRBs) to anxiety, but their specific associations in preschool children with ASD remain unclear. This study explored the nature of anxiety and its connections with related factors using a network analysis approach. METHODS: This cross-sectional questionnaire study included 660 preschool children (288 with ASD and 372 neurotypical children). Standardized instruments assessed anxiety, IU, SOR, and RRBs. Gaussian graphical models were estimated using the GLASSO approach in R. Expected influence and bridge expected influence were calculated to identify the central and bridge nodes; network differences between groups were examined. RESULTS: (1) Worry about separation (A10); sweating or breathing difficulty (A7); avoidance of transportation (A15); and avoidance of darkness, crowds, heights, storms, or water (A17) were central nodes in the ASD anxiety symptom network. (2) IU, rigidity/adherence to routine, and SOR were bridge nodes in ASD anxiety and related factor networks. (3) ASD and neurotypical groups differed in network structure across networks, but only the anxiety symptom network differed in global strength. A15 and IU differed in expected influence and bridge expected influence, respectively. CONCLUSION: These findings provide insight into anxiety symptoms and related factors in preschool children with ASD and may inform our understanding of anxiety and support for this population.
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27. Manasevich V, Kostanian D, Sysoeva O. Neurophysiological Processing of Rise Time in Children with Autism Spectrum Disorder. Brain Sci. 2026; 16(10).
BACKGROUND: Amplitude rise time is a critical acoustic cue for speech perception, yet its neurophysiological processing remains uninvestigated in autism spectrum disorder characterized by communication deficits, sensory abnormalities and often speech delay. This study examined whether children with autism spectrum disorder differ from typically developing peers in auditory event-related potential components across a continuum of rise times. METHODS: Electroencephalography was recorded during passive presentation of pure tones with five rise time values (15, 30, 60, 120, 240 ms) in 42 children (21 with autism spectrum disorder, 21 typically developing, aged 4-10 years). Linear mixed models were used to analyze latencies and amplitudes of P1 and N2 components. RESULTS: Children with autism spectrum disorder showed a less systematic pattern of neural modulation across rise times compared to typically developing peers. P1 amplitude was reduced at 15 and 60 ms (trend at 30 ms), with no significant group differences at longer rise times. N2 latency showed an atypical decrease at 60 ms compared to 30 ms, contrasting with the systematic increase observed in typically developing children. P1N2 amplitude reached a minimum at 60 ms in autism spectrum disorder, whereas typically developing children showed a gradual decrease across rise times. CONCLUSIONS: These findings provide the first evidence of atypical neurophysiological processing of rise time in children with autism spectrum disorder, with the most pronounced differences in the range of rapid acoustic onsets. Group differences were not detected at longer rise times, suggesting a selective rather than global deficit in temporal envelope processing.
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28. Marques AR, Martiniano H, Vilela J, Vicente AM. miR4ASD: A Database of Human microRNAs Associated with Autism Spectrum Disorder. Curr Issues Mol Biol. 2026; 48(10).
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by substantial etiological and clinical heterogeneity. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in brain development. As such, a growing body of work suggests a role of miRNA dysregulation in several human pathologies of the brain, including ASD. However, evidence on miRNA involvement in ASD is dispersed across the literature, limiting its utility for biomarker discovery and functional insights. Here, we present miR4ASD, a manually curated and open-access database of human miRNAs implicated in ASD, covering data from case-control studies of both gene expression and genetic variant analysis. This resource integrates structured data from peer-reviewed publications, including study methodology, tissue type, expression alteration (upregulated or downregulated), sample size, number of supporting studies, and reported genetic variants within miRNA genes. To ensure objectivity and precision, 59 studies meeting the strict inclusion criteria were included. miR4ASD also integrates miRNA-target interaction data from external resources and allows users to perform functional enrichment analysis of target genes. By providing a dynamic and accessible platform, miR4ASD enables the systematic exploration of miRNA involvement in ASD and supports research in diagnostics, biomarker discovery, and systems biology. The database is publicly available on GitHub.
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29. Modrzejewska M, Skonieczna-Żydecka K, Modrzejewska A, Zdanowska O, Połubiński P, Bosy-Gąsior W, Grzesiak W. Variability in Refractive Measurements in Children with Autism Spectrum Disorder Under Cycloplegic and Non-Cycloplegic Conditions: Influence of Measurement Method. J Clin Med. 2026; 15(20).
Purpose: To compare refractive measurements obtained with Retinomax K-plus 3 and Plusoptix A09 V in children with autism spectrum disorder (ASD) before and after cycloplegia and to assess inter-device agreement. Methods: This retrospective pilot study included 23 children with ASD (mean age 6.54 ± 2.83 years), of whom 14 underwent examination with two autorefractometers (Retinomax K-plus 3 and Plusoptix A09 V) before and after cycloplegia induced with 1% tropicamide. Direct inter-device comparisons were restricted to the 14 children with paired measurements and were performed using the Wilcoxon signed-rank test, with matched-pairs rank-biserial correlations reported as effect sizes. Agreement in spherical equivalent (SE) was assessed using Bland-Altman analysis. Cycloplegia-induced refractive shifts were compared between devices. Secondary comparisons with controls without documented neurodevelopmental disorders (n = 27) were restricted to Retinomax SE measurements and performed using analysis of covariance (ANCOVA), with age included as a continuous covariate. Results: Before cycloplegia, Retinomax showed significantly more myopic SE values than Plusoptix in both eyes (right eye [OD]: -1.21 ± 1.25 vs. 0.91 ± 0.67 D; left eye [OS]: -1.22 ± 1.15 vs. 0.77 ± 0.51 D; both p < 0.00417). Significant inter-device differences in SE persisted after cycloplegia (OD: 0.63 ± 0.94 vs. 2.00 ± 0.63 D; OS: 0.46 ± 0.96 vs. 1.98 ± 0.63 D; both p < 0.001). Bland-Altman analysis showed a systematic negative bias of Retinomax relative to Plusoptix, which decreased after cycloplegia but persisted (before: -2.12 D for OD and -1.99 D for OS; after: -1.37 D and -1.52 D, respectively). Cycloplegia-induced shifts were greater with Retinomax; however, the between-device differences were not statistically significant after Bonferroni correction. In secondary analyses, age-adjusted Retinomax SE remained significantly lower in the ASD group than in controls without documented neurodevelopmental disorders before and after cycloplegia (all p < 0.001). Conclusions: In this exploratory cohort of children with ASD, Retinomax measurements were associated with more myopic SE values than Plusoptix, particularly before cycloplegia. The inter-device bias decreased but persisted after cycloplegia. This reduction is compatible with a contribution of accommodation; however, the persistence of the bias after cycloplegia indicates that device-specific measurement characteristics should also be considered. Refractive measurements obtained with the two autorefractometers should therefore not be assumed to be directly interchangeable. These findings underscore the importance of cycloplegic control and careful interpretation of autorefractor measurements in children with ASD. Larger prospective studies are warranted.
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30. Mutlu MB, Sanrı A, Yaralı O, Sezer Ö, Kılıçaslan F, Gümüş H, Kumandaş S, Öz Ö. Whole-exome sequencing in a Turkish autism spectrum disorder cohort: a retrospective study of molecular diagnostic yield in isolated and complex presentations. BMC Psychiatry. 2026; 26(1).
BACKGROUND: Whole-exome sequencing (WES) can identify molecular etiologies in autism spectrum disorder (ASD), particularly when ASD occurs with developmental delay/intellectual disability (DD/ID), epilepsy, dysmorphism, congenital anomalies, or neuroimaging abnormalities. Data on WES yield and candidate-gene findings in Turkish ASD cohorts remain limited. We assessed molecular diagnostic yield and variant spectrum in a Turkish clinical ASD cohort, with comparison of isolated and complex ASD presentations. METHODS: This retrospective cohort study included 320 individuals with ASD evaluated by WES between 2020 and 2025. Patients were classified as having isolated or complex ASD based on co-occurring neurodevelopmental, neurological, dysmorphic, congenital, or systemic findings. Variants were interpreted using ACMG/AMP criteria. Established molecular diagnoses required pathogenic or likely pathogenic (P/LP) variants associated with OMIM-defined disorders or occurring in genes with definitive, strong, or moderate ClinGen evidence for a neurodevelopmental disorder (NDD). Categorical comparisons used two-sided Fisher’s exact test. RESULTS: Established molecular diagnoses were identified in 104/320 patients (32.5%; 95% confidence interval [CI], 27.4-37.9%), including 2/22 patients with isolated ASD (9.1%; 95% CI, 1.1-29.2%) and 102/298 patients with complex ASD (34.2%; 95% CI, 28.9-39.9%; p = 0.017). An additional 12 patients had P/LP variants in candidate or emerging genes, resulting in an overall P/LP finding rate of 116/320 (36.3%; 95% CI, 31.0-41.8%). Variants of uncertain significance were identified in 147 patients, while no ASD/NDD-related variant was identified in 57 patients. CONCLUSIONS: WES supports etiological clarification in clinically complex ASD. Established molecular diagnoses were substantially more frequent in complex than isolated ASD. Candidate and emerging gene findings should be reported separately and interpreted as hypothesis-generating.
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31. Nam JH, Lee HS. Associations Between Upright Cardiovascular-Autonomic Characteristics, Temporal Gait Measures, and Mediolateral Plantar Center-of-Force Measures in Adults with Developmental Disabilities: An Exploratory Cross-Sectional Study. Medicina (Kaunas). 2026; 62(10).
Background and Objectives: Adults with developmental disabilities may show altered gait and autonomic regulation, but their relationship during upright function remains unclear. This study examined associations between upright cardiovascular-autonomic characteristics, temporal gait measures, and mediolateral plantar center-of-force (COF) measures and secondarily compared intellectual disability (ID) and autism spectrum disorder (ASD) groups. Materials and Methods: This cross-sectional study included 24 adults. Measures were the change in heart rate from supine to standing (ΔHR), standing root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and normalized high-frequency power [HF (nu)]. F-Scan 3-Box outputs from three 6-meter walks provided eight gait measures, including trial-to-trial coefficients of variation (CV) and symmetry index (SI) of temporal variables. Thirty-two primary partial rank correlations were adjusted for age, sex, and body mass index (BMI), with Benjamini-Hochberg false discovery rate (BH-FDR) correction. Results: Standing HF (nu) and stride time SI showed a nominally significant negative association (partial ρ = -0.663, unadjusted p = 0.0071; 95% CI [-0.877, -0.227]), but this association did not remain significant after BH-FDR correction (q = 0.228). No primary association survived FDR correction. Additional adjustment for diagnosis yielded ρ = -0.672 (unadjusted p = 0.0085). Standing RMSSD and stance time CV were not significantly associated (ρ = -0.527, p = 0.053). No primary gait measure differed significantly between ASD and ID. Conclusions: The observed standing HF (nu)-stride time SI association is exploratory and did not survive correction for multiple testing. The findings do not establish stronger temporal than spatial associations, clinical benefit, or a causal mechanism. Larger studies with detailed heart rate variability (HRV) and gait-event measurements are needed.
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32. Niccolini B, Grandi M, Nobile V, Pucci C, Boldrin F, Clementi ME, Bottoni P, Riente A, Chiurazzi P, Neri G, Genuardi M, Baracca A, Maulucci G, Tabolacci E, Giorgio V. Mitochondrial Remodeling and Impaired Bioenergetics Define Neuronal Vulnerability in Fragile X-Related Disorders. Antioxidants (Basel). 2026; 15(10).
Fragile X syndrome (FXS) and related conditions associated with FMR1 gene alterations have increasingly been linked to mitochondrial dysfunction, although most available evidence derives from peripheral cell models. Whether these abnormalities also occur in disease-relevant neuronal populations remains largely unknown. Building on our previous observations in patient-derived fibroblasts, we investigated mitochondrial structure and function in neurons differentiated from induced pluripotent stem cells (iPSCs) generated from individuals with FXS and carriers of unmethylated full mutations, using matched healthy control lines. Mitochondrial integrity, bioenergetic properties, and network organization were evaluated to determine whether FMR1-associated mitochondrial defects are preserved in a neuronal context. Mitochondrial abnormalities previously identified in fibroblasts were recapitulated in iPSC-derived neurons. These findings demonstrate that impaired mitochondrial dynamics and function are conserved across different cell types, indicating that mitochondrial dysfunction represents a relevant cellular feature of FXS and related FMR1-associated conditions. Our results indicate that mitochondrial dysfunction is a shared feature of FMR1-related neuronal models, while the underlying patterns of mitochondrial remodeling are influenced by the specific FMR1-associated condition. These results support a role for mitochondrial alterations in FMR1-related neuronal dysfunction and provide a basis for the further investigation of the mechanisms linking mitochondrial homeostasis to the pathophysiology of FXS and related conditions.
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33. Pérez N, Bellver A, Hussain F, Huerta-Ramos E, Tous N, Frye RE, Griñán-Ferré C. Epigenetic Hierarchies in Autism from Folate-SAM Metabolism to LSD1 and G9a. Biomolecules. 2026; 16(10).
Autism spectrum disorder (ASD) is a diverse neurodevelopmental condition involving interactions among genetic, environmental, metabolic, immune, synaptic, and epigenetic factors. This review explores whether disruptions in folate-dependent one-carbon metabolism and S-adenosylmethionine (SAM) availability may increase epigenetic susceptibility in specific ASD subgroups based on biological criteria. This narrative, hypothesis-driven review synthesizes selected peer-reviewed literature encompassing human studies, animal models, cell systems, and biochemical research. Findings including decreased methylation capacity, altered DNA methylation, and abnormal histone methylation have been reported in ASD and related neurodevelopmental conditions. Nonetheless, evidence strength varies considerably depending on phenotype, tissue type, developmental stage, and experimental system. On this basis, a provisional SAM-dependent epigenetic hierarchy is proposed in which methyltransferases may differ in vulnerability to metabolic stress according to enzyme kinetics, subcellular context, developmental timing, and compensatory regulation. This model is conceptual rather than an established mechanism demonstrated uniformly across ASD. Clinical and translational findings are interpreted cautiously. Evidence for folinic acid is strongest in selected subgroups such as folate receptor alpha autoantibody-positive ASD and cerebral folate deficiency-related presentations, whereas LSD1/KDM1A and G9a/EHMT1/2 modulation remains largely preclinical. Overall, the review argues that folate-SAM-related epigenetic dysregulation may represent one contributory pathway in some ASD subgroups and provides a framework for future mechanistic and stratified therapeutic studies.
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34. Pezone M, Garotti R, Sgueglia E, Siracusano R, Maffettone V, Avitabile C, Maisto A, Bravaccio C, Riccio MP. Sex-Related Specificities of Sensory Profiles in Autism Spectrum Disorder: Impact on Clinical Functioning. Medicina (Kaunas). 2026; 62(10).
Background and Objectives: Sensory anomalies are a distinctive feature of Autism Spectrum Disorder (ASD) individuals and appear to differ in intensity, frequency, and subtype between male and female subjects. According to the diagnostic framework of the DSM-5-TR, these sensory patterns are key clinical indicators. The objectives of this study were to investigate sensoriality in ASD, to compare sensory profiles in ASD subjects of both sexes and evaluate potential correlations with clinical profiles. Materials and Methods: A total of 94 ASD participants were enrolled at the Children and Adolescents Neuropsychiatry Department of the University of Naples Federico II. The population was assessed through psychometric (cognitive and adaptive levels, and intensity of autism symptoms) and sensory characterization (using the Short Sensory Profile questionnaire). Subsequently, a Mann-Whitney U test was performed to evaluate differences in sensory profiles between males and females. Spearman’s correlation was used to assess significant associations between the sensory profile and cognitive level, adaptive level, and ASD symptom intensity. Subsequently, for the correlations that emerged as significant, an analysis was performed using a General Linear Model (GLM), including age and Intelligence Quotient (IQ) as covariates in the model. Results: No statistically significant differences in the sensory profile emerged between male and female subjects. Sensory anomalies do not appear to be correlated with cognitive level. Although some statistically significant correlations emerged between the sensory profile, the AQ, and the ADOS-2 comparison score, these results were not confirmed after a GLM analysis was performed using the participants’ age and IQ as covariates. Conclusions: The observed results appear partially in line with the existing literature. Following the GLM analysis, it was further observed that variables such as age and IQ play a crucial role in interpreting the functional profile of individuals with ASD. At present, the study has several limitations (the exclusive use of parent-report instruments, an observational design, the lack of a control group) which could affect the robustness of the observed findings. Therefore, further studies are deemed necessary to better define the sex-specific sensory characteristics of ASD individuals.
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35. Rose S, Melnyk S, James SJ, Frye RE. Effect of Leucovorin on Mitochondrial Respiration and One-Carbon Metabolism in Autism Spectrum Disorder: A Double-Blind Placebo-Controlled Substudy. Int J Mol Sci. 2026; 27(20).
Mitochondrial dysfunction and impaired methylation are implicated in autism spectrum disorder (ASD). Leucovorin, a reduced folate that bypasses both dihydrofolate reductase and folate receptor alpha, has shown clinical benefit in small trials in children with ASD, but the underlying biology is incompletely understood. In this pre-specified biomarker substudy of a completed double-blind placebo-controlled trial (NCT02000284; NCT01602016), children with ASD received leucovorin (2 mg/kg/day, maximum 50 mg/day) or a matched placebo for 12 weeks. Peripheral blood mononuclear cell respiration was measured by extracellular flux with a graded 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) challenge (38 participants; 17 leucovorin, 21 placebo) and plasma thiol-methylation metabolites were measured pre- and post-treatment (42 participants; 18 leucovorin, 24 placebo). Leucovorin increased basal, ATP-linked, proton-leak, maximal, and reserve respiration relative to the placebo (Group × Visit p ≤ 0.012, all q ≤ 0.012; Cohen’s d 0.48-0.92); there was no evidence that the treatment effect varied across the tested DMNQ concentrations. In exploratory moderator analyses, folate receptor alpha autoantibody (FRAA) status modified the effect on maximal respiratory capacity and reserve capacity (both p < 0.001), with the largest gains in FRAA-positive children receiving leucovorin, and a history of neurodevelopmental regression modified the effect on basal, proton-leak and reserve respiration. The plasma SAM/SAH ratio increased (d = 0.77) and S-adenosylhomocysteine decreased (d = -0.67) on leucovorin; both were nominally significant (p = 0.020 and 0.050) but neither survived false-discovery-rate correction within the thiol family. The findings support the folate-mitochondrial-redox axis as a candidate therapeutic target in ASD and warrant replication in larger independent cohorts.
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36. Rousan MJ, McGonigle T, Muscatello RA, Vandekar S, Corbett BA. Differences in Reporting Suicidality Among Autistic Girls: Comparing Parent-, Child Self-, and Clinician-Rated Child Self-Reports Between Distinct Measures. J Autism Dev Disord. 2026.
PURPOSE: Suicidality in autistic girls is an emerging albeit understudied concern, driven by elevated internalizing symptoms, socio-emotional challenges, and limited autism-sensitive assessments. This study examined diagnostic (autistic vs. non-autistic), informant (parent-, written child self-, clinician-rated child self-report), and measure (written self-report (CDI-2) vs. verbal interview (C-SSRS and K-SADS)) differences in suicidality. It was hypothesized that (1) suicidality would be reported more in autistic than non-autistic girls, and (2) written child self-report would yield the highest suicidality endorsement rate, followed by parent- and clinician-rated child self-report. METHODS: Participants consisted of 213 autistic (N = 112) and non-autistic (N = 101) girls aged 6-13. Suicidality was assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS; parent-report), the Children’s Depression Inventory, Second Edition (CDI-2; written child self-report), and the Columbia Suicide Severity Rating Scale (C-SSRS; clinician-rated child self-report). RESULTS: Across informants/measures, autistic girls had three times greater odds of endorsing suicidality than non-autistic peers (OR = 3.05, 95% CI [1.64, 5.67], p < 0.001). Written child self-report yielded the highest endorsement, while parent- (OR = 0.51, 95% CI [0.32, 0.82], p = 0.006) and clinician-rated child self-report (OR = 0.39, 95% CI [0.24, 0.64], p < 0.001) were less likely to capture suicidality. CONCLUSIONS: Findings highlight the role of child self-report in detecting suicidality among autistic girls and suggest that multi-informant, autism-informed approaches utilizing both written and verbal response methods can reduce underestimated risk and facilitate timely intervention.
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37. Rubbi I, Lupo R, Rosa G, Greco GM, Marchisio D, Panzanaro L, Cucci F, Calabrò A, Conte L, Dellafiore F, Artioli G, Vitale E. Knowledge of Childhood Autism and Care Experiences in Critical Settings: A Survey Among Italian Nurses. J Autism Dev Disord. 2026.
OBJECTIVES: This study examined nurses’ knowledge of childhood autism and their experiences caring for autistic patients in emergency and critical care. The Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire is child-focused, whereas the care-experience questions were age-neutral. METHODS: From May to July 2025, 503 nurses and nurse coordinators recruited by non-probability convenience sampling completed an online survey with socio-demographic items, the 19-item KCAHW, and study-specific closed- and open-ended questions. Non-parametric group comparisons reported effect sizes with bootstrap confidence intervals. Open-text responses underwent content analysis. RESULTS: Using the original scoring key, the mean KCAHW score was 15.96/19 (SD = 2.54); at least 80% scored a point on 16 items, but only 39.8% recognized atypical eating patterns. Differences by sex, age, professional experience, educational level, geographic area, and clinical setting were mostly small, the largest being between clinical settings (ε² = 0.133-0.195). Care experiences told a different story: 74.0% reported difficulties in caring for autistic people, 90.9% felt not at all or not very prepared, and 91.1% had never attended ASD-specific training. The most frequent difficulty was communication and relational problems (58.6% of 266 answers). A crisis had been managed by 56.3%; of 133 accounts, 58.6% involved caregivers or the team and 15.8% medication, sedation, or restraint. Only 54.7%-55.7% routinely chose a quiet setting, avoided noise, or adapted lighting. CONCLUSION: Participants recognized much of the KCAHW’s childhood-autism content, but this did not translate into perceived preparedness. Practice-oriented education is needed, together with tools that assess professional competence across the lifespan.
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38. Rusu RV, Delcea C. Autism in Criminal-Justice and Forensic Settings: A Systematic Review and Meta-Analysis with an Exploratory Bidirectional Synthesis. Behav Sci (Basel). 2026; 16(10).
BACKGROUND: Estimates of autism in criminal-justice and forensic populations vary widely, while studies involving autism-defined populations report heterogeneous justice outcomes. Broad pooling can obscure differences in recruitment, diagnostic ascertainment, legal context, and outcome definition. METHODS: We conducted a systematic review and meta-analysis addressing two complementary questions: the proportion of autistic people in defined criminal-justice and forensic populations (Axis A) and criminal-justice outcomes within autism-defined populations (Axis B). Searches covered PubMed/MEDLINE, Lens.org, NCJRS, Scopus, Web of Science Core Collection, and ProQuest Central Premium, supplemented by citation searching. Compatible exact-count proportions were synthesized using binomial generalized linear mixed models with profile-likelihood confidence intervals; inverse-variance REML models with modified Hartung-Knapp inference were used for sensitivity analyses. RESULTS: The reconciled register contained 300 candidate reports, 161 retained reports, and 37 selected numerical contributions from 30 reports representing 29 source-study units. Only three clinically compatible Axis A strata supported pooling. Estimated proportions of autism were 23.57% (95% CI 10.67-42.69) in specialist forensic intellectual-disability services, 0.89% (0.36-2.23) in general forensic responsibility evaluations, and 23.51% (20.10-27.08) in forensic youth referral services. Each synthesis contained two cohorts, and modified Hartung-Knapp intervals were substantially wider. General-prison administrative estimates ranged from 0.62% to 1.09%. Axis B findings differed by endpoint, population, sex, observation period, and adjustment set and were therefore not pooled. CONCLUSIONS: Autism frequency in justice and forensic settings is strongly setting- and ascertainment-dependent. The evidence does not support a single criminal-justice prevalence estimate or a unitary association between autism and offending. Clinically and legally defined populations should be synthesized separately, with explicit management of cohort overlap and diagnostic definitions.
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39. Sallum BT, de Figueiredo MGC, Haddad MEO, Santos WS, Cordeiro ML. Advancing Standardization in Fragile X Syndrome Molecular Diagnosis: A Dual-Structured and Scoping Review. Children (Basel). 2026; 13(10).
Background: Fragile X syndrome (FXS) requires molecular confirmation, yet diagnostic workflows vary in their capacity to characterize expansions and connect diagnosis with subsequent care. This review evaluated alignment between current recommendations and published diagnostic practice. Methods: We combined a structured review of recommendations for FMR1 molecular diagnosis, complementary testing, genetic counseling, and family testing with a scoping review of peer-reviewed primary studies reporting FMR1 diagnostic or screening workflows relevant to pediatric FXS. PubMed/MEDLINE, Embase, and Scopus were searched without date restrictions. Thirty-four studies were included, with design-specific risk-of-bias assessment and exploratory exact analyses of factors associated with post-initial FMR1 testing. Results: Molecular or genomic testing was reported in all 34 studies, but workflows ranged from conventional PCR and Southern blot to TP-PCR, methylation-sensitive assays, and sequencing-based approaches. Post-initial FMR1 testing was reported in 22/34 studies (64.7%), with positive-result follow-up documented in 19/34 (55.9%) and follow-up of inconclusive or initially negative results in 14/34 (41.2%). FMR1 sequencing was uncommon (3/34, 8.8%). Genetic counseling was addressed in 32/34 studies (94.1%), but documented as delivered in only 9/34 (26.5%); family evaluation and multidisciplinary management were also inconsistently reported. Conclusions: Published evidence broadly supports molecular FMR1 testing but shows variability in molecular characterization and downstream care. Standardization should prioritize analytically appropriate workflows, additional testing when required by the initial result or assay limitations, and stronger integration of molecular diagnosis with genetic counseling, family evaluation, and multidisciplinary management.
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40. Sammon M, O’Connor S, Carey C. Autism in a general adult mental health service in Ireland: prevalence, clinical presentation, and service use. Ir J Psychol Med. 2026: 1-7.
BACKGROUND: Autistic adults experience high rates of co-occurring mental health difficulties, yet little is known about their representation within secondary adult mental health services. This study aimed to examine the actual prevalence and clinical presentation of autistic adults attending a community general adult mental health service in Ireland. METHODS: A cross-sectional retrospective chart review was conducted in July 2023 within a community-based secondary mental health service serving a population of 92,610. Demographic characteristics, autism-related factors, diagnoses, self-harm/suicidality, and multidisciplinary service utilisation were extracted and analysed using descriptive and inferential statistics. RESULTS: Forty autistic service users were identified among a total caseload of 1,270 (3.1%). The median age was 23 years, and 67.5% were male. Most autism diagnoses (65%) were made through Child and Adolescent Mental Health Services. Psychotic disorders were the most common psychiatric diagnosis (30%), followed by mood and anxiety disorders. Over half (52.5%) had a history of self-harm and/or suicidality, and 17.5% had required psychiatric inpatient admission. Although 95% were referred to at least one multidisciplinary team (MDT) service, 30% did not attend these appointments. CONCLUSIONS: Autistic adults represented a small proportion of service users despite their high burden of mental health difficulties, suggesting possible underrecognition of autism and barriers to accessing secondary mental health services. Those receiving care demonstrated complex clinical needs, including high rates of psychosis and suicidality. Improving autism recognition, developing integrated care pathways, and adapting multidisciplinary services to better meet autistic adults’ needs are essential to delivering equitable mental healthcare.
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41. So J, Chen YR, Wilkes-Gillan S, Parsons L, Spender K, Cordier R. From Self-Regulation to Function: A Systematic Review and Meta-Analysis of Randomised Controlled Trials in Autistic Children and Young People. Children (Basel). 2026; 13(10).
Background and Objectives: Self-regulation is important for children’s learning, social participation and everyday functioning, yet intervention evidence for autistic children and young people is fragmented across intervention approaches and regulatory constructs. This systematic review and meta-analysis aimed to characterise and critically evaluate non-pharmacological randomised controlled trials targeting self-regulation in autistic children and young people and to quantify effects on both self-regulation and separate child functional outcomes. Methods: MEDLINE, PubMed, PsycINFO, CINAHL and ERIC were searched to 24 May 2026. Eligible studies were randomised controlled trials involving autistic children and young people aged 0-18 years that targeted at least one domain of self-regulation and assessed both self-regulation and child function. Risk of bias was assessed using RoB-2. Random-effects meta-analyses were conducted for self-regulation and functional outcomes, with moderator, meta-regression and sensitivity analyses examining sources of variation. Functional proximity and intervention-mechanism moderator analyses were exploratory and were not prespecified in the registered protocol. Results: Twenty-five studies involving 1655 randomised participants were included. Self-regulation improved significantly across 27 intervention-comparator effects from 25 studies (Hedges’ g = 0.605, 95% CI 0.454-0.756; 95% prediction interval 0.027-1.183). Functional outcomes also improved across 25 effects from 23 studies (g = 0.527, 95% CI 0.356-0.698; 95% prediction interval -0.158-1.212). Functional effects were substantially larger for direct/target-aligned outcomes (g = 0.761) than for distal/generalisation outcomes (g = 0.250; Q(β) = 11.034, p < .001). The direct-distal contrast attenuated when restricted to active-comparator studies (Q(β) = 3.770, p = .052), although distal effects remained positive. Comparator type moderated both outcome streams, whereas self-regulation construct coverage, age, intervention duration, target-skill application and explicit generalisation support did not significantly moderate effects. Conclusions: Self-regulation-focused interventions produce beneficial average effects on both regulatory and functional outcomes. Functional improvement is strongest when outcomes align closely with intervention targets, although smaller positive effects also extend to distal outcomes. Future trials should distinguish proximal regulatory change from target-aligned and distal functional outcomes and explicitly test pathways of generalisation.
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42. Ünlü Ö. The Effectiveness of a Technology-Supported Behavioral Intervention Package for Teaching Earthquake Safety Skills to Children with Autism Spectrum Disorder: A Multiple-Probe Single-Case Evaluation. Behav Sci (Basel). 2026; 16(10).
Children with autism spectrum disorder (ASD) are at heightened risk during earthquakes, yet behavioral interventions targeting disaster preparedness in this population remain scarce. This study evaluated the effects of a multicomponent, technology-supported behavioral intervention package on the acquisition, maintenance, and generalization of earthquake safety skills-declarative knowledge of pre- and post-earthquake actions and a five-step drop-cover-hold chain under stimulus control-in children with ASD. Three male children with ASD (aged 8-12 years) took part in a probe-condition multiple-probe across-participants single-case experimental design. The package combined video modeling, slide-based concept presentation, conditional discrimination training, and in vivo rehearsal with least-to-most prompting and reinforcement schedule thinning. All three participants reached the maximum score after three to four instructional sessions and met the mastery criterion (three consecutive maximum scores) within six to seven daily probes. Performance was maintained at 2-, 4-, and 8-week follow-up probes, with one score of 4 at 4 weeks, and generalized to a novel setting, materials, and implementer. Visual analysis indicated three within-study replications of effect, one per participant, produced by the staggered introduction of the intervention across the three tiers of the design, and Tau-U effect sizes were 0.80 to 0.87 (large to very large). Within the limits of a three-participant design meeting What Works Clearinghouse standards with reservations, these findings indicate that structured behavioral instruction can establish earthquake safety responding in children with ASD; replication is required before wider instructional use.
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43. Wu C, Yu Y, Liang H, Wang Z, Li W, Li Z, Ye X, Ren J, Wang M, Ma L. Association between maternal thyroid function in early pregnancy and neurodevelopment in children aged 0-24 months: a retrospective cohort study. BMC Pregnancy Childbirth. 2026; 26(1).
BACKGROUND: To investigate the influence of maternal thyroid function in early pregnancy on offspring neurodevelopment outcomes. METHODS: We retrospectively analyzed 20,855 mother-offspring pairs from Shenzhen, China, with delivery dates between February 2016 and May 2024. Maternal thyroid hormone levels were measured at 7-13 gestational weeks. Neurodevelopment outcomes were assessed using the Ages and Stages Questionnaire-Third Edition (ASQ-3) at 0-24 months of age. RESULTS: Compared with euthyroid mothers, overt hypothyroidism was associated with an increased risk of gross motor delay (adjusted odds ratio [aOR] 2.14; 95% confidence interval [CI] 1.17-3.63). Subclinical hypothyroidism was linked to a higher risk of delay in the problem-solving domain (aOR 1.63; 95% CI 1.03-2.49). Hypothyroxinemia was associated with increased risk of delays in both the gross motor (aOR 1.73; 95% CI 1.04-2.70) and fine motor domains (aOR 1.69; 95% CI 1.01-2.66). Subclinical hyperthyroidism was associated with an elevated risk of gross motor delay (aOR 1.97; 95% CI 1.14-3.18). Maternal thyroid-stimulating hormone (TSH) levels exhibited a U-shaped relationship with the risk of neurodevelopmental delay in the gross motor domain. (P-overall = 0.012; P-nonlinear = 0.003) CONCLUSIONS: Maternal overt hypothyroidism, subclinical hypothyroidism, hypothyroxinemia, and subclinical hyperthyroidism in early pregnancy are associated with neurodevelopmental delays in children. Notably, this association exhibits a U-shaped pattern, whereby both low and high TSH levels are linked to an increased risk of neurodevelopmental delay.
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44. Zhang S, Yan Y, Wang M, Wei J, Ma X, Yang X. Comparative Effectiveness of Probiotics, Prebiotics, and Synbiotics for Symptoms of Autism Spectrum Disorder: A Systematic Review and Network Meta-analysis. Nutr Rev. 2026.
CONTEXT: Autism spectrum disorder (ASD) is characterized by impaired social interaction, communication deficits, and repetitive behaviors. Increasing evidence suggests that gut microbiota may be a potential therapeutic target. However, the relative efficacy of single-strain probiotics, multistrain probiotics, prebiotics, and synbiotics remains unclear. OBJECTIVE: This network meta-analysis aims to systematically compare the effectiveness of these microbiota-targeted interventions on ASD symptoms. DATA SOURCES: A systematic search of PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted up to June 20, 2025. DATA EXTRACTION: Randomized controlled trials (RCTs) assessing single-strain probiotics, multistrain probiotics, prebiotics, or synbiotics in individuals with ASD were included. The primary outcome was the improvement in deficits in core ASD symptoms, such as social communication and interaction and restricted and repetitive behaviors, which were assessed using standardized tools. DATA ANALYSIS: A Bayesian network meta-analysis with random-effects modeling was performed. Seventeen RCTs involving 904 participants were included. Synbiotics showed greater efficacy in improving ASD symptoms compared with placebo (standardized mean difference [SMD]: -1.90; 95% credible interval [CrI]: -2.66 to -1.06), prebiotics (SMD: -2.23; 95% CrI: -3.10 to -1.06), multistrain probiotics (SMD: -1.59; 95% CrI: -2.41 to -0.68), and single-strain probiotics (SMD: -1.52; 95% CrI: -2.40 to -0.60). The sensitivity analyses were generally consistent with the primary findings. CONCLUSION: Synbiotics appeared to demonstrate greater efficacy than probiotics, prebiotics, and placebo in improving behavioral symptoms of ASD. However, given the limited available evidence and modest sample sizes, this finding should be interpreted cautiously and considered preliminary. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD420251078170.
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45. Zheng X, Tan R, Wang Y, Jiang Y, Guo Y, Cheng Y, Liu Y, Qiu S. Association of Copy Number Variations in PTEN with Autism Spectrum Disorder. Genes (Basel). 2026; 17(10).
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic basis. While copy number variations (CNVs) significantly contribute to ASD risk, the specific role of individual genes within these variants remains unclear. This study investigates the contribution of CNVs in the PTEN gene to ASD pathophysiology by integrating population-level genetic analysis with multi-dimensional biological evidence. Methods: The biological plausibility of PTEN in ASD was first assessed using public multi-omics data, including tissue expression profiles, protein-protein interaction networks, and published cell-type-specific differential-expression data derived from single-nucleus RNA sequencing. Subsequently, a group-matched case-control study was conducted in a Han Chinese population (121 ASD cases and 110 controls) to evaluate the association between PTEN CNVs and ASD susceptibility. One-way ANOVA was performed to compare the differences in ASD clinical phenotype scores among groups with different CNV types of PTEN. Results: Integrative biological analyses revealed that PTEN is enriched in ASD-relevant brain regions (e.g., cerebellum) and exhibits cell-type-specific expression in neurons and glia. Furthermore, protein network analysis confirmed its central position within the PI3K/AKT signaling pathway, a critical regulator of neurodevelopment. In the Han Chinese population, no significant association was detected between PTEN CNVs and ASD risks or clinical phenotype scores. Conclusions:PTEN CNVs may not be independently associated with ASD, but may contribute to susceptibility through broader neurodevelopmental networks and molecular pathways.
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46. Zheng Z, Ji M, Liang Y, Pan S. Efficacy of stem cell-derived extracellular vesicles in animal models of autism spectrum disorder: a systematic review and meta-analysis. Front Psychiatry. 2026; 17: 1956214.
BACKGROUND: Autism spectrum disorder (ASD) is a complicated neurodevelopmental condition that currently lacks a targeted therapy. Although stem cell-derived extracellular vesicles (EVs) represent a potential therapeutic approach for neurological disorders, their efficacy in ASD remains unclear. The objective of this study was to investigate the efficacy of stem cell-derived EVs on autistic-like behaviors in animal models of ASD and to explore the underlying mechanisms. METHODS: Relevant studies published up to April 20, 2026 were searched across five databases. Data were pooled using Review Manager 5.4. Outcome measures included behavioral tests and inflammatory cytokine levels. RESULTS: Out of 1,165 initially retrieved articles, five animal studies met the inclusion criteria. Pooled analyses demonstrated that EV treatment improved autistic-like behaviors in the self-grooming test, three-chamber social interaction test, and marble burying test, and decreased levels of proinflammatory cytokines IL-6 and IL-1β (all P < 0.05). No notable enhancements were observed for the open field test, Morris Water Maze, TNF-α or IL-10 (all P > 0.05). CONCLUSION: Stem cell-derived EV therapy may improve repetitive behaviors and social deficits in ASD animal models, with observed associations with reduced IL-6 and IL-1β levels. These preclinical findings suggest promising translational potential of EV-based therapy for ASD. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/c78xm, identifier 10.17605/OSF.IO/C78XM.
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47. Zhu M, Zhang JF, Hu SX, Wang X, Xu W. Shared Genetic and Regulatory Architecture of Congenital Heart Disease and Autism Spectrum Disorder Revealed by Cross-Tissue Multi-Omic Integration. Genes (Basel). 2026; 17(10).
Background: Congenital heart disease (CHD) and autism spectrum disorder (ASD) co-occur more frequently than expected, suggesting shared developmental susceptibility. We aimed to identify cross-tissue molecular candidates linking cardiac and neurodevelopmental abnormalities. Methods: CHD- and ASD-associated genes were curated from MalaCards and SFARI Gene, and their intersection was defined as the CHD- and ASD-associated gene set (CAGES). Shared gene enrichment was assessed against the human protein-coding genome. CHD and ASD genome-wide association data were integrated with heart and brain cis-expression quantitative trait loci using Bayesian colocalization and summary data-based Mendelian randomization with HEIDI testing. Candidates were further evaluated using bulk transcriptomics, six machine learning feature selection methods, independent cohorts, and scTenifoldKnk virtual knockout analyses in developing human heart and cerebral cortex. Results: Seventy-three genes were shared between CHD and ASD. CHD7 showed suggestive colocalization for CHD and ASD, while lower genetically predicted CHD7 expression was associated with higher odds of both disorders, with nonsignificant HEIDI tests. MEF2C was downregulated in tetralogy of Fallot myocardium and selected by all six ASD machine learning methods, with consistently lower expression in ASD. CAGES-derived signatures discriminated independent CHD, ASD cord blood, and cortical cohorts. CHD7 virtual knockout analysis identified MEF2C as a computationally predicted regulatory candidate in the prenatal brain, particularly in late-fetal excitatory neurons and intermediate progenitor cells, with cell-type-specific predicted effects also observed in the developing heart. Conclusions: CHD and ASD share molecular susceptibility involving pleiotropic developmental mechanisms. CHD7 and MEF2C emerge as connected cross-tissue candidates across complementary genetically informed, transcriptomic, and developmental regulatory analyses, highlighting prenatal neuronal populations and developmental windows for investigating the heart-brain axis.