1. Belisário Bizutti Fernandes C, McNally Keehn R, Keehn B. Hand Leading in Autism: Associations With Neurocognitive Profiles and Adaptive Abilities. Autism Dev Lang Impair. 2026; 11: 23969415261487874.

BACKGROUND: Hand-leading (HL) gestures used to obtain assistance or direct another person’s actions are often reported at elevated rates in autistic children. Yet, their developmental significance and relation to children’s broader cognitive and adaptive profiles remain poorly understood. This study examined the presence and developmental correlates of HL gestures in a sample of toddlers and young children referred for autism evaluation. METHODS: Participants were 156 toddlers and young children aged 18-48 months (111 autistic [86 male, 25 female]; 45 non-autistic with other developmental concerns [28 male, 17 female]). Children were assessed using the Mullen Scales of Early Learning to derive verbal and nonverbal developmental quotients (DQs) and a nonverbal-verbal difference score. Adaptive functioning was measured using the Vineland Adaptive Behavior Scales. Autism symptoms were indexed using the Autism Diagnostic Observation Schedule (ADOS-2) and a DSM-5-based caregiver interview/clinician checklist. HL gestures, defined as physically directing others, were operationalized by creating a composite score of items from the ADOS-2 and caregiver/clinician reports, which was scaled from 0 to 100 and dichotomized to indicate clear use of HL gestures. RESULTS: HL gestures were observed more frequently in autistic than non-autistic children. Within the autism group, HL gesture use was associated with higher autism symptom severity and lower verbal DQ but was unrelated to age, sex, nonverbal ability, or adaptive functioning. Higher nonverbal-to-verbal developmental abilities uniquely predicted greater HL gesture use. Use of HL gestures also predicted stronger daily living but not adaptive communication or socialization skills. CONCLUSIONS: Use of HL gestures appears more closely linked to language level than to general developmental delay. They may reflect adaptive, goal-directed communicative strategies rather than autism-specific social-communication impairments, particularly among those with relatively stronger nonverbal than verbal abilities. IMPLICATIONS: These findings highlight heterogeneity in autistic communication profiles and support viewing HL gestures as functional behaviors that may scaffold early daily living skills.

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2. Caldwell-Harris CL. Autistic interests: wide-ranging and intellectually oriented. Front Psychiatry. 2026; 17: 1749552.

INTRODUCTION: The interests of autistic individuals have traditionally been described as circumscribed and restricted, serving the functions of self-regulation by reducing prediction error. Historically, this may have seemed reasonable when applied to autistic children and adults with intellectual disability. The current study investigated the restrictiveness and function of focused interests of autistic adults with typical intellectual ability. METHODS: To hear from autistic adults themselves, bypassing interviewers’ agendas, online discussion posts were analyzed from threads that opened with questions such as What are your special interests? Content analysis was utilized to categorize the special interest topics into a taxonomy (e.g., Academic, Entertainment) and to code for functions, including knowledge seeking (systemizing), mastery, self-regulation, and socializing. Word frequency analyses tallied terms associated with intellectual content and intensity, to evaluate whether interests serve knowledge-seeking vs self-regulation. RESULTS: Academic topics dominated the interests mentioned, appearing in approximately half of all posts, with psychology-related topics being the most frequent, appearing in 29% of posts. Interests were often highly specific, but were frequently the opposite of restricted. Many posts described a large, diverse range of interests, spanning disparate domains, which was labeled wide-ranging intellectual appetite. Knowledge seeking emerged as the primary function, with 52% of posts containing relevant terms (e.g., learn, read, research). Intellectual approaches to an interest were frequently reported even for non-academic topics like fictional worlds, cooking, pets and true crime. Posts describing the purpose of interests as self-regulation appeared in 9% of posts, career, 6% of posts, and socializing, 4% of posts. DISCUSSION: The findings challenge the traditional deficit perspective by demonstrating that focused interests in autistic adults are characterized by knowledge seeking, a construct similar to systemizing, but more explicitly on a continuum with academic interests. These interests are not restricted but wide-ranging, resembling the explorations of polymaths. The established view, that intense interests reduce anxiety by promoting predictability, originated in historical attention to autistic individuals with atypical intellectual ability. Intellectual disability obscured how repetitive behaviors such as object manipulation are ‘experiments to see’. I propose that knowledge-seeking is the primary function of systemizing and intense interests, thus unifying focused interests across multiple levels of intellectual ability of the autism spectrum.

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3. Davidson E, Khan S, Rhee C, Hoffman EJ. Leveraging Scalable Non-Mammalian Systems for Large-Scale Studies of Autism Risk Gene Function. Biol Psychiatry. 2026.

There are over 100 large-effect genes strongly associated with autism spectrum disorder (ASD), yet advancing from risk genes to the discovery of common biological pathways and pharmacological targets remains a central challenge. Scalable non-mammalian systems, including Caenorhabditis elegans (roundworm), Drosophila melanogaster (fruit fly), Danio rerio (zebrafish), and Xenopus tropicalis (frog), provide critical advantages for the functional analysis of ASD genes due to their amenability to high-throughput screens, relatively low cost, and ease of genetic manipulation. Recent studies have leveraged the unique strengths of these systems to address critical challenges in ASD genetics by analyzing the function of human rare variants, evaluating interactions among genes in ASD-associated copy number variants, and investigating multiple ASD genes in parallel. These studies revealed that ASD genes play conserved roles in the neural circuits underlying basic learning, sensory processing, sleep, and social behaviors. Also, they uncovered common biological pathways uniting ASD genes, including neurogenesis, microtubule biology, and mitochondrial function. Interestingly, pharmacological suppressor screens in non-mammalian systems identified estrogenic compounds as modulators of ASD gene-associated phenotypes. Furthermore, by enabling the parallel in vivo analysis of >100 ASD genes, these systems facilitate the identification of ASD gene subgroups with shared biological effects, a critical step in drug discovery. Therefore, non-mammalian systems are emerging as key players along with mammalian and human cellular systems in the search for convergent mechanisms downstream of ASD genes and the discovery of precision medicine-based treatments.

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4. Elsayed HAE, Alanazi SA, Saleh MSM. Quality of Life and Specific Difficulties of Children with Autism Spectrum Disorder Among Saudi Primary Caregivers. Healthcare (Basel). 2026; 14(17).

BACKGROUND: The prevalence of autism spectrum disorder (ASD) is increasing globally and in Saudi Arabia (SA), although many cases remain undiagnosed. Caregivers of children with ASD are confronted by challenges, especially mothers as primary caregivers, who have higher levels of stress and burden of care due to autism symptoms and difficulties of children, which negatively affects their quality of life (QoL). OBJECTIVE: The primary outcome of this study was to assess primary caregivers’ quality of life and their perceptions of child-related difficulties associated with autism spectrum disorder (ASD) using the Quality of Life in Autism (QoLA) questionnaire. The secondary outcome was to examine the correlation between these two QoLA domains and identify the factors independently associated with each outcome Material and Methods: A convenience sample (247) of Saudi primary caregivers, primarily mothers, was taken from autism primary schools in Tabuk, Riyadh, Qassim, Hail, Jazan & Najran cities in SA by distributing an online questionnaire, which was composed of three parts, was used for data collection; Part I included demographic and clinical data of primary caregivers. Part II: The child’s personal characteristics. Part III: QoLA Questionnaire that measures the crucial aspects of living with autistic children and is composed of two parts (A and B). Data analysis was performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA), version 23. RESULTS: More than half of the caregivers (50.2%) had a moderate level of QoL. Regarding caregivers’ perceptions of child-related difficulties, 70.9% reported high levels of difficulties, and 7.2% reported low difficulties. Quality of life was significantly associated with maternal age, educational level, number of children. The study’s univariate regression and multivariate regression analysis revealed that, QoL score had a significant negative association with maternal ages, university school and secondary school, working, and those who had medical diseases. In contrast, QoL level had a significant positive association with mothers who received training, had another person helped in caring for the child and who had enough income. CONCLUSIONS: Mothers of autistic children had poorer QOL and perceived more difficulties in caring for their children. Thus, educating sessions for mothers about dealing with their autistic children, psychological and financial support services are needed, which in turn improve their QoL.

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5. Focșa IO, Iliescu C, Pomeran C, Budișteanu M, Sandu C, Dică AD, Lincă FI, Moțoiescu C, Bârcă D, Minciu I, Craiu D, Rădoi VE. RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine. Int J Mol Sci. 2026; 27(17).

Genetic neurodevelopmental disorders (NDDs) encompass a heterogeneous group of conditions characterized by impaired cognitive, behavioral, and neurological development resulting from pathogenic variants affecting brain development and synaptic function. Advances in molecular genetics and next-generation sequencing have significantly expanded the understanding of the genetic architecture underlying disorders such as Rett syndrome (RTT), Fragile X syndrome (FXS), Angelman syndrome (AS), and autism spectrum disorders. Beyond these classical neurodevelopmental disorders, spinal muscular atrophy (SMA) is included as a paradigmatic example of successful RNA-based therapeutic translation. Concurrently, RNA-based therapeutics have emerged as promising precision medicine strategies capable of modulating gene expression at the transcriptional and post-transcriptional levels. These approaches include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), messenger RNA (mRNA) therapies, RNA editing technologies, and splice-modulating agents. Recent clinical successes, particularly in spinal muscular atrophy, have demonstrated the transformative potential of RNA therapeutics in neurological disease. However, substantial challenges remain, including BBB penetration, long-term safety, immune activation, and genotype-specific variability in therapeutic response. This review summarizes current advances in RNA-based therapeutics for genetic NDDs, highlighting molecular mechanisms, disease-specific therapeutic strategies, translational progress, delivery challenges, and future directions. Overall, continued progress will depend on the integration of disease biology, rational RNA therapeutic design, and effective CNS-targeted delivery, supporting the broader implementation of precision RNA medicine for genetic neurodevelopmental disorders.

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6. Ganai UJ, Bhushan B. Developmental milestones and resting-state functional connectivity: Shared and distinct associations with neurodevelopmental traits. Psychol Med. 2026; 56: e277.

BACKGROUND: Early motor and language milestones are key indicators of neurodevelopment, yet their associations with later autism traits and attention-deficit/hyperactivity disorder (ADHD) symptoms remain poorly understood. Neurobiological mechanisms linking early developmental delays to these conditions are not well established. Here, we investigate associations between early developmental milestones, resting-state functional connectivity (rsFC), and neurodevelopmental traits in a large adolescent sample. METHODS: Data were drawn from the Adolescent Brain Cognitive Development study (ABCD) and included 6,663 participants (age range = 8.92-11.08 years; mean age = 9.92 years; 48.42% female). Developmental measures included roll over, sit without assistance, walk without assistance, speech development, gross motor development, and coordination. Autism traits were assessed using the Social Responsiveness Scale, and ADHD symptoms were assessed using the Attention Problems subscale of the Child Behavior Checklist. rsFC was examined within and between cortical and subcortical regions. Linear mixed-effects (LME) models and Bayesian mediation analyses assessed associations between developmental measures, rsFC, and neurodevelopmental traits. RESULTS: LME models revealed shared and condition-specific associations. Poor coordination was associated with higher autism traits and ADHD symptoms, whereas delayed speech development was associated with autism traits, and delayed walking without assistance with ADHD symptoms. We found negligible evidence that rsFC measures mediated associations between early developmental milestones and neurodevelopmental traits. Indirect effects were modest, accounting for less than 2% of associations with autism traits, although somewhat larger effects were observed for ADHD symptoms. CONCLUSIONS: These findings suggest overlapping developmental pathways, with intrinsic connectivity reflecting downstream neural processes rather than primary mediating mechanisms.

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7. Govender P, Livingstone RW, Hidalgo-Robles Á, Schomerus R, Leite HR, Paleg G. Applying an F-words lens to planning intervention for a child with autism: a retrospective case report with prospective follow-up. Front Psychiatry. 2026; 17: 1905890.

Children with Autism Spectrum Disorder (ASD) present with complex, multi-domain functional challenges that single-domain intervention approaches fail to address adequately. This retrospective case report, with prospective follow-up from age 7 years, applies CanChild’s F-words and the F-words Lens Tool to examine intervention planning and developmental outcomes across a five-year trajectory for an eight-year-old autistic girl with co-occurring hypotonia and joint hypermobility. For each developmental period, from 24 months to eight years, we identify the functional challenge encountered, drawing on standardized assessment data (CELF Preschool, Renfrew Action Picture Test, ADOS-2) alongside clinical and family report, and describe how F-words thinking informed clinical decision-making in real time; the F-words Lens Tool, developed subsequently, is applied here, retrospectively for earlier periods and prospectively from age 7, to structure this reasoning transparently, specify the interventions selected and their cross-domain rationale, and report outcomes. The case traces the child’s trajectory through the early developmental period, and following transition to mainstream schooling with presenting strengths and challenges. Caregiver accounts (father, grandmother) and the child’s own first-person perspective provide the lived experience outcomes across F-words domains. Together, this triangulated account demonstrates how the F-words and F-words Lens Tool can enhance clinical decision-making and family collaboration while preserving child agency, contributing an example to the global discourse on evidence-based, family-centred practice in complex neurodevelopmental presentations.

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8. Haghighat H. A Neuroinformatics Framework for Evaluating Functional Connectivity Metrics in Small-Sample Resting-State fMRI: An Age-Stratified Autism Study. Neuroinformatics. 2026; 24(3).

Functional connectivity (FC) analysis using resting-state fMRI is widely applied to study brain organization in autism spectrum disorder (ASD). However, variability in FC estimation, limited sample sizes, and high-dimensional feature spaces often produce unstable and over-optimistic machine-learning results, highlighting the need for rigorous methodological benchmarking. We propose a neuroinformatics framework for systematic evaluation of multiple FC measures under small-sample rs-fMRI conditions. Data were analyzed across children, adolescents, and adults. Group independent component analysis followed by dual regression extracted subject-specific network time series. Five FC measures-full correlation, partial correlation, bivariate Granger causality, coherence, and mutual information-captured linear, nonlinear, time-, and frequency-domain interactions. To ensure leakage-aware evaluation, feature selection was performed strictly within training folds using leave-one-out cross-validation, and multiple machine-learning classifiers were used as standardized evaluation tools. Performance of FC measures varied across developmental stages. Linear connectivity measures showed more stable behavior in childhood, nonlinear information-theoretic measures were most informative in adolescence, and frequency-domain measures demonstrated stronger performance in adulthood. Unlike studies focused primarily on diagnostic accuracy, this work emphasizes comparative methodological evaluation and explicitly addresses data leakage and overfitting through strict cross-validation and training-only feature selection. FC-based machine-learning outcomes are strongly influenced by developmental stage and methodological choice. The proposed leakage-aware framework provides a practical benchmark for evaluating FC measures in small-sample rs-fMRI Studies and supports more reliable neuroimaging machine-learning research.

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9. He L, He R, Liu G, Liu S, He X. Art-based interventions and social-emotional outcomes in children with autism spectrum disorder: a systematic review and meta-analysis with a proposed neurodevelopmental framework. Front Hum Neurosci. 2026; 20: 1941559.

Emotional intelligence (EI)-related social-emotional difficulties in children with autism spectrum disorder (ASD) are linked to atypical social-brain development, including altered amygdala-prefrontal, fusiform, and frontoparietal function during affective processing. This systematic review and meta-analysis quantified the effects of visual art-based interventions on EI and EI-related social-emotional outcomes in children with ASD, and integrated convergent neuroimaging evidence into a testable neurodevelopmental framework. Following PRISMA 2020, PubMed, Web of Science, PsycINFO, the Cochrane Library, ProQuest Dissertations, ClinicalTrials.gov, and gray literature were searched from inception to 31 December 2025, with an updated search on 15 May 2026 and a supplementary public-source update on 17 August 2026. Eligible studies included controlled, quasi-experimental, or pre-post visual art-based interventions lasting at least 4 weeks in children aged 3-18 years with clinically diagnosed ASD. Risk of bias was assessed using RoB 2.0 and ROBINS-I, and Hedges’ g was pooled using random-effects models. Fourteen studies involving 521 participants aged 3-15 years across seven countries were included; 481 participants were children with autism spectrum disorder and 40 were typically developing comparison participants. Twelve studies used a control group and formed the basis of the primary analysis. Art-based interventions were associated with a small-to-moderate improvement in EI-related social-emotional outcomes (all studies: k = 14, SMD = 0.47, 95% CI [0.30, 0.63], p < 0.001; controlled studies only: k = 12, SMD = 0.46, 95% CI [0.28, 0.64]), with no detectable statistical heterogeneity [I (2) = 0, 95% prediction interval (0.28, 0.65)]. Exploratory subgroup analyses showed no material difference between multimodal and drawing-focused programs (p = 0.79) and a larger point estimate for interventions lasting 9-16 weeks, but these moderator findings were descriptive and should be interpreted cautiously. Under the GRADE approach the certainty of the evidence was rated low. Neuroimaging evidence suggests that visual art engagement may support EI through frontoparietal attentional control, graded affective exposure, and prefrontal regulation of limbic reactivity. Direct longitudinal neuroimaging trials are needed to test these proposed mechanisms.

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10. Hou J, Fang Y, Wang Y, Wen S. The impact of non-invasive brain stimulation and digital intervention on social cognitive therapy in autism spectrum disorder: a systematic review and network meta-analysis. Front Psychiatry. 2026; 17: 1877176.

INTRODUCTION: To evaluate the relative efficacy of non-invasive brain stimulation (NIBS) and digital interventions for improving social cognition in autism spectrum disorder (ASD). METHODS: A systematic search of PubMed, Embase, Web of Science, Cochrane, CNKI to February 2026 yielded 50 randomized controlled trials (RCTs). A Bayesian network meta-analysis was performed using R, ranking interventions via Surface Under the Cumulative Ranking curve (SUCRA) and assessing evidence certainty with Confidence in Network Meta-Analysis (CINEMA). RESULTS: Across the included trials (mean age range: 2.54 to 20.80 years), among 9 interventions, transcranial direct current stimulation (tDCS) emerged as optimal (SUCRA = 88.24%), significantly outperforming treatment as usual (TAU) (SMD=-1.69, 95% CrI: -2.67, -0.70). This was followed by high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) (84.38%, SMD=-1.60, 95% CrI: -2.32, -0.89), low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) (74.22%, SMD=-1.36, 95% CrI: -1.77, -0.96), and theta-burst stimulation (TBS) (64.21%, SMD=-1.19, 95% CrI: -2.02, -0.35); all significantly outperformed TAU. Standalone digital interventions ranked lower. Meta-regression showed no significant age moderating effect. CONCLUSIONS: tDCS is the most efficacious standalone intervention for ASD social cognitive deficits. We recommend tDCS or TBS clinically and advocate a synergistic paradigm integrating NIBS neural priming with digital training. However, future large-scale, rigorous RCTs are required to further validate both these standalone modalities and the proposed combined protocols. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337491, identifier CRD420261337491.

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11. Kamal M. Commentary: Autism screening and diagnosis in children with congenital heart disease. Front Pediatr. 2026; 14: 1936706.

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12. Kawar K. Cultural, familial, and technological factors influencing AAC implementation for non-speaking autistic children in the Arab community in Israel. Augment Altern Commun. 2026: 1-12.

This study examined the cultural, familial, educational, and technological factors influencing how Arab parents of non-speaking autistic children understand and implement augmentative alternative communication (AAC) within their sociocultural context in the Arab community in Israel. Although AAC can enhance communication, participation, and emotional expression, it remains underused in many minority and multilingual communities. Using a qualitative, phenomenologically informed design and reflexive thematic analysis, the study involved in-depth guided semi-structured interviews with 20 Arab parents of non-speaking autistic children (ages 6-9). Trustworthiness was supported through triangulation, peer debriefing, reflexive memos, and member checks. Five overarching themes were identified: (1) parental attitudes, emotions, and meaning-making around AAC; (2) the central role of the family and sociocultural environment, including stigma and extended-family influences; (3) institutional and educational factors shaping AAC exposure, training, and continuity; (4) linguistic and technological accessibility, particularly the scarcity and limited cultural fit of Arabic-language AAC tools; and (5) parental agency and resilience amidst structural constraints and cultural expectations. Findings underscore that AAC implementation is culturally situated and structurally constrained, highlighting the need for culturally responsive AAC training, Arabic- and dialect-sensitive AAC resources, and coordinated systemic support for Arab families in Israel.

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13. Lee H, Kim S, Ahn S, Lee W, Hwang JW, Jo E, Kim WJ. Prenatal exposure to particulate matter and risk of autism spectrum disorder in children: a population-based cohort study in South Korea. Environ Res. 2026; 306(Pt 2): 125161.

BACKGROUND: Prenatal exposure to particulate matter has been investigated as a potential environmental factor for autism spectrum disorder (ASD), but evidence remains heterogeneous, and nationwide data from non-Western populations are limited. METHODS: We conducted a nationwide retrospective birth cohort study using the Big CHildren’s ENvironmental health Study (Big-CHENS) database in South Korea, including 698,907 mother-father-child pairs born between 2015 and 2017 and followed through 2023. Prenatal exposure to PM(2.5) and PM(10) was estimated using machine learning-based models and averaged over the entire pregnancy and by trimester. ASD was identified using diagnostic codes, with abnormal findings from the Korean Developmental Screening Test. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) per interquartile range increase in pollutant concentrations after adjusting for a broad range of potential confounders. RESULTS: During follow-up, 5594 children (0.8%) were diagnosed with ASD. Prenatal PM(2.5) exposure was not associated with ASD risk during the total pregnancy period (HR, 0.99; 95% CI, 0.95-1.03) or during the first (1.02, 0.99-1.05), second (0.99, 0.97-1.02), or third trimester (0.98, 0.95-1.00). Similarly, prenatal PM(10) exposure was not associated with ASD risk during the total pregnancy period (0.99, 0.94-1.04) or during the first (1.02, 0.98-1.05), second (0.99, 0.96-1.02), or third trimester (0.98, 0.96-1.01). Findings were consistent across developmental screening outcomes, subgroup analyses, and sensitivity analyses. CONCLUSIONS: In this nationwide South Korean cohort, prenatal exposure to PM(2.5) or PM(10) was not associated with ASD risk after accounting for a broad range of potential confounders. These findings highlight the importance of careful confounder control and outcome definition in studies of prenatal air pollution exposure and neurodevelopmental outcomes.

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14. Leisman G, Melillo R. Toward a Developmental Timing Framework for Autism: Linking Hemispheric Asymmetry, Motor Organization, and Motor-Social Coupling. J Integr Neurosci. 2026; 25(9): 54429.

Early behavioral features associated with autism spectrum disorder (ASD) are frequently examined within separate motor, sensory, and social domains rather than as interacting components of a developing neurobiological system. In this article, we present a hypothesis-driven conceptual framework proposing that variation in developmental timing and coordination across neural, motor, and interpersonal systems may contribute to differences in early social developmental trajectories. Drawing on evidence from fetal, infant, and early childhood development, we consider how hemispheric specialization, interhemispheric coordination, oscillatory synchronization, corticalization of motor control, and dyadic interaction timing may jointly influence the emergence of motor organization and social engagement. From this perspective, persistent primitive reflex expression, atypical motor asymmetry, increased motor variability, and differences in dyadic synchrony are discussed as candidate developmental indicators that may reflect broader variation in neural timing and coordination. Within this framework, we further consider how genetic, neurobiological, and environmental factors associated with ASD risk may converge on developmental timing processes expressed through neural communication, motor regulation, and social interaction. Rather than proposing a deterministic causal sequence, the present account examines how variation in motor-social interaction may influence opportunities for social learning through recurrent cycles of action, perception, prediction, and caregiver feedback. We advance a set of empirically testable developmental hypotheses linking neural timing measures, motor organization indices, reflex integration profiles, and dyadic interaction metrics within prospective longitudinal research designs. Specifically, the framework predicts that variation in early neural timing and coordination will be associated with differences in motor organization and motor-social coupling, which may in turn relate to later social developmental outcomes. By emphasizing developmental timing, coordination, and reciprocal interaction across neural, motor, and interpersonal systems, this conceptual framework is intended not as a causal account of ASD, but a hypothesis-generating developmental model that organizes existing evidence while generating explicit, empirically testable predictions regarding relationships among neural timing, motor organization, and early social interaction.

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15. Lichtiger L, Yeung E, Lin TC, Putnick DL, Sundaram R, Bell EM, Rahman MM, Thurston GD, Wang Y, Ghassabian A. Air pollution and autism-like traits: Sensitive periods and joint effects of exposure to sources and constituents of fine particulate matter. Environ Res. 2026; 306(Pt 2): 125213.

Growing evidence suggests that exposure to air pollution during early life is associated with autism spectrum disorder (ASD). However, results have been inconsistent for autism-like traits and in low exposure settings. Here, we assessed sensitive windows of exposure to fine particulate matter (PM(2.5)), nitrogen dioxide (NO(2)), and ozone (O(3)) and joint effects of exposure to sources and constituents of PM(2.5) on autism-like traits among 798 children in the Upstate KIDS cohort. Residential air pollution exposures were assessed with machine learning and land use regression models. Autism-like traits at age 10 were assessed via the ASD subscale on the Child Behavior Checklist. Treed distributed lag mixture model was used to identify critical windows of exposure to PM(2.5), NO(2), and O(3) and partial linear single index model was applied to estimate contributions of sources and constituents of PM(2.5) on autism-like traits. The median PM(2.5) exposures were 8.36 and 8.00 μg/m(3) for pregnancy and the first year of life. We did not observe critical windows of exposure to PM(2.5), NO(2), or O(3) for autism-like traits. Exposures to elemental carbon (EC) PM(2.5) during gestation and to EC and traffic PM(2.5) during the first year of life were associated with higher odds of autism-like traits (prenatal EC adjusted odds ratio (aOR): 1.72, 95% CI: 1.04-2.83; first year EC aOR: 1.72, 95% CI: 1.21-2.46; traffic aOR: 1.31, 95% CI: 1.01-1.71). Our results suggest that exposure to motor vehicle traffic sources of PM(2.5) may drive previously reported associations between total PM(2.5) and autism-like traits.

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16. Lin Z, ShangGuan Y, Sim YJ, Jia X, Deng X, Qing Y, Huang Y, Yao Y, Zhang W. Interpretable machine learning for predicting moderate-to-severe insomnia risk in Chinese adults with autism spectrum disorder. Front Psychiatry. 2026; 17: 1898010.

OBJECTIVE: To develop a risk prediction model for moderate-to-severe insomnia among adults with autism spectrum disorder (ASD) and to identify key predictive features using interpretable machine learning methods, to support exploratory risk estimation and stratification. METHODS: This study used data from the 2024 Psychological and Behavioral Survey Database of Adults with ASD and included 976 adults with ASD in the final analysis. Moderate-to-severe insomnia was defined as an Insomnia Severity Index (ISI) score ≥ 15. To avoid outcome leakage, all ISI items and the ISI total score were excluded from the predictor set, and sleep-related items were also removed from the depression and anxiety symptom scores. The dataset was first divided into training and test sets at a ratio of 7:3 using stratified random sampling. Candidate predictors were subsequently selected using least absolute shrinkage and selection operator regression based exclusively on the training set, and multicollinearity was assessed using the variance inflation factor (VIF). For models requiring feature scaling, standardization parameters were estimated from the training data only and subsequently applied unchanged to the test data. Nine machine learning models were developed using the training set and evaluated in the independent test set. The final model was interpreted using SHAP, and an online prediction tool was developed based on important variables. RESULTS: Among the 976 adults with ASD, 265 participants (27.2%) were classified as having moderate-to-severe insomnia. After LASSO selection using the training set, 18 predictors were retained, and no substantial multicollinearity was observed. In the held-out test set, logistic regression achieved a ROC AUC of 0.7262 and a PR AUC of 0.4624, compared with a no-skill precision-recall baseline of approximately 0.273. At the operating threshold used for classification, sensitivity was 0.4875, specificity was 0.8216, and accuracy was 0.7304, which was similar to the no-information rate of 0.7270. SHAP analysis showed that the total score of the non-sleep items of the GAD-9, the total score of the non-sleep items of the PHQ-8, anxiety diagnosis, proportion of screen time spent watching short videos, age, and sex were among the predictors with higher contributions. CONCLUSION: This study developed an interpretable prediction model for moderate-to-severe insomnia risk among adults with ASD. Anxiety- and depression-related symptoms were the main predictive features, while the proportion of screen time spent watching short videos also provided additional predictive value. The online tool developed based on key variables may provide an exploratory approach to individualized risk estimation and stratification, but further validation and threshold optimization are required before it can be considered for screening applications.

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17. Luan Y, Zhang H, Ma N, Zhang Y, Xu Z, Zhang W, Zhang X, Liu Y. HK2 drives synaptic dysfunction in fragile X syndrome via epigenetic regulation of H3K18 lactylation. Front Pharmacol. 2026; 17: 1903604.

INTRODUCTION: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by loss of fragile X messenger ribonucleoprotein (FMRP) expression and characterized by synaptic dysfunction and cognitive impairment. However, the metabolic and epigenetic mechanisms underlying these abnormalities remain poorly understood. To address this gap, this study investigated the role of hexokinase 2 (HK2) in FXS pathogenesis and explored downstream metabolic and epigenetic mechanisms associated with synaptic dysfunction and cognitive impairment. METHODS: Using an Fmr1 (-/Y) mouse model, we evaluated HK2 expression and its cell-type specificity in hippocampal neurons. RNA immunoprecipitation (RIP) analysis was performed to examine the association between FMRP and Hk2 mRNA. Genetic knockdown of HK2 was used to assess its effects on neurite outgrowth, synapse density, synaptic transmission, and hippocampal long-term potentiation (LTP). Finally, pharmacological experiments using the HDAC3 inhibitor RGFP966 were performed to examine whether modulation of H3K18la levels contributes to HK2-associated phenotypes. RESULTS: HK2 expression was markedly elevated in hippocampal neurons of Fmr1 (-/Y) mice. RIP analysis revealed an association between FMRP and Hk2 mRNA, suggesting that HK2 may represent an FMRP-associated transcript. Genetic suppression of HK2 promoted neurite outgrowth, increased synapse density, and improved synaptic transmission and hippocampal long-term potentiation (LTP) in Fmr1 (-/Y) mice. Mechanistically, HK2 knockdown selectively reduced H3K18la levels without affecting H3K18 acetylation, supporting a role for HK2 in regulating histone lactylation. Consistent with these findings, pharmacological inhibition of HDAC3 with RGFP966 increased H3K18la levels and attenuated the beneficial effects of HK2 suppression on neuronal morphology, synaptic plasticity, and cognitive function. Behavioral analyses demonstrated that modulation of the HK2-H3K18la axis improved spatial learning and memory in Fmr1 (-/Y) mice. CONCLUSION: Taken together, these findings support a role for the HK2-H3K18la axis in synaptic dysfunction in FXS. Targeting this metabolic-epigenetic axis may provide a potential avenue for future therapeutic exploration in FXS and related neurodevelopment disorders.

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18. Morozova KN, Wolf ER, Kiseleva EV, Smirnov AV, Pershina EG, Pristyazhnyuk IE. Modeling Cohen Syndrome in Phoenix Cells: VPS13B Loss Causes Organelle Stress, G1/S Delay, and Fibrillary Inclusion Bodies Formation. Cells. 2026; 15(17).

Cohen syndrome, caused by pathogenic variants in VPS13B, is characterized by microcephaly, developmental delay, and progressive retinal degeneration, yet the cellular mechanisms linking VPS13B dysfunction to disease pathology remain incompletely understood. Here, we used CRISPR-Cas9 to delete VPS13B exons 2-4 in Phoenix HEK293 cells, generating five independent knockout clones. In all mutant lines, VPS13B disruption caused a marked slowing of cell proliferation due to prolongation of the G1 phase. Immunocytochemistry and transmission electron microscopy revealed that VPS13B mutations causes Golgi apparatus fragmentation, loss of VPS13B Golgi localization, ER lumen dilation with rigid membrane morphology, mitochondrial damage, impaired autophagic maturation, and the appearance of cytoplasmic fibrillary inclusions located close to ER and absent from control cells. RNA-seq analysis identified 27 differentially expressed genes common to all four mutant clones, including downregulation of genes involved in transcriptional regulation, lipid metabolism, and neuronal signaling, alongside upregulation of the stress-response genes CLU and CDKN1A (p21). While our results do not support classical unfolded protein response activation, they are consistent with a model in which lipid bilayer stress and disrupted ER-Golgi trafficking may play a role in the pathophysiology of Cohen syndrome. Together, these findings demonstrate that VPS13B deficiency results in coordinated defects in organelle homeostasis, proteostasis, and cell-cycle progression, providing new dates for understanding Cohen syndrome pathogenesis.

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19. Nordstrand M, Falk SF, Johansson M, Pestoff R, Tammimies K. Assessing Swedish genetic counselling outcome measures for autism and general use: Rasch findings highlight the need for improved measures. BMC Psychol. 2026; 14(1).

BACKGROUND: Genetic counselling outcome measures are increasingly adapted for diverse clinical contexts. While the Genetic Counselling Outcome Scale (GCOS-24) is available in Swedish, no autism-specific version has been developed. METHODS: We adapted the Swedish GCOS-24 using the English version of the modified GCOS-24 (mGCOS-24) to create a Swedish autism-specific mGCOS-24. Thereafter, we evaluated both the Swedish autism mGCOS-24 and the Swedish general GCOS-24 using Rasch analysis to assess their psychometric properties. RESULTS: Both instruments exhibited structural challenges, including multidimensionality, disordered thresholds, local item dependence, and invariance issues. For the Swedish autism mGCOS-24, we were able to identify subscales with acceptable measurement properties. However, applying the same structure to the Swedish general GCOS-24 did not resolve its broader limitations. CONCLUSIONS: This study introduces the first Swedish autism‑specific mGCOS‑24 and represents the first Rasch‑based evaluation of any GCOS‑24 or mGCOS‑24 in Swedish. Our findings highlight important opportunities for outcome measure refinement but also indicate that new or more substantially adapted tools may be needed to capture outcomes of genetic counselling in autistic populations.

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20. Petrick LM, Dassanayake PS, Gennings C, Guan H, Akintunde B, Martinez M, Regmi P, Hertz-Picciotto I, Arora M, Bennett DH. Fetal exposure to persistent organic pollutants and childhood autism risk. Environ Res. 2026; 306(Pt 2): 125179.

Exposure to persistent organic pollutants (POPs) during fetal development may increase the risk of autism spectrum disorder, but previous studies have relied on maternal pregnancy samples as proxies instead of directly measuring fetal exposures. Here, we used naturally shed deciduous teeth from autism cases and typically developing controls born between 1998 and 2014 from the California, USA, population-based case-control Childhood Autism Risk from Genetics and the Environment study. Using gas chromatography-tandem mass spectrometry, we quantified fetal second and third trimester and postnatal POPs in teeth dentine. In total, seven polychlorinated biphenyls, two organochlorine pesticides, and four brominated diphenyl ethers were quantified in deciduous teeth. We compared children clinically confirmed to have autism with typically developing children from the general population using logistic regression for exploratory single chemical analysis and Weighted Quantile Regression Analysis for mixture analysis. In the third trimester, the POPs mixture was positively associated with autism (median Odds Ratio (OR) = 1.54 (95% CI = [0.99, 2.83]). In sex-stratified interaction analysis, the OR for males (median = 1.75) was significant (95% CI: [1.13, 3.2]), while the OR for females was small (1.16) and not significant (95% CI = [0.33, 3.5]). The POPs mixtures during the second trimester or postnatally were not significantly associated with autism risk. Therefore, direct fetal and early-life measures of POPs indicate the third trimester as a potential high-risk biological window for POPs exposures that increase autism risk, particularly in males.

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21. Rast JE, Anderson KA, Killian MO, Radey M. Preventable Hospitalizations During the COVID-19 Pandemic in Patients With Autism and Without Autism. Intellect Dev Disabil. 2026; 64(5): 400-13.

During the COVID-19 pandemic, hospitalizations decreased due to the reallocation of health care resources to support pandemic mitigation efforts and social changes in risk exposure, including preventable hospitalizations for the escalation of conditions that could be better treated within primary care. The purpose of this study was to examine changes in and characteristics of preventable hospitalizations over the COVID-19 period for patients withand without autism using 2019 to 2021 data from the National Inpatient Sample. Overall counts of preventable hospitalizations decreased at the start of the pandemic across groups, while the proportion of hospitalizations that were preventable remained relatively stable. The proportion of hospitalizations that were preventable was higher for children and adults with autism than children and adults without autism, and this remained consistently elevated through out the study period. This study helps evaluate how disparities evolve under conditions of healthcare system stress, providing insight into the resilience and inclusiveness of crisis-era health system responses.

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22. Rodeiro-Boliart J, Nuñez-Jimenez M, Olaya B, Huerta-Ramos E, Golobardes E. An interpretable computational phenotyping pipeline for adult autism using routine electronic health records. Front Psychiatry. 2026; 17: 1952612.

INTRODUCTION: Electronic health records (EHRs) provide new opportunities for computational phenotyping in mental health, but routinely collected diagnostic data are often sparse, heterogeneous, and challenging to interpret. While numerous computational approaches have been applied to identify patient subgroups, clinically useful phenotyping requires workflows capable of transforming routine diagnostic information into interpretable patient profiles. The goal of this work is to develop and evaluate an end-to-end computational phenotyping pipeline for routine ICD-10 diagnostic data and demonstrate its feasibility in adults with autism spectrum disorder (ASD). METHODS: A retrospective observational study was conducted using routine EHR data from adults with ASD receiving care at a specialized mental health service. ICD-10 diagnoses were extracted, aggregated into clinically meaningful diagnostic categories, and transformed into binary patient-level representations. A self-organizing map (SOM) was used to organize patients according to diagnostic similarity, followed by hierarchical clustering to identify phenotype groups. Cluster solutions were evaluated using internal validity metrics, cluster size distributions, and interpretability. The resulting phenotypes were identified through diagnostic prevalence profiles and SOM-based visualizations. RESULTS: The study included 927 adults with ASD, of whom 744 presented at least one comorbid diagnostic category and were included in the computational phenotyping analysis. The proposed pipeline identified four phenotypes characterized by distinct patterns of psychiatric and developmental comorbidity. The SOM structure provided an interpretable visualization of the diagnostic landscape, while hierarchical clustering enabled the identification of coherent phenotype groups. Internal validation metrics supported the selected solution while preserving informative subgroup sizes. DISCUSSION: This study presents an end-to-end computational phenotyping pipeline that transforms routinely collected psychiatric EHR data into interpretable patient phenotypes. By integrating diagnostic extraction, clinically informed aggregation, representation learning, clustering, visualization, and characterization, the workflow provides a practical framework for analyzing complex diagnostic data in real-world mental health settings. Future studies should evaluate its applicability across other psychiatric and neurodevelopmental populations.

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23. Salviati S, Braccagni G, Corridori E, Sabatini G, Fanti F, Guzzi F, Parenti M, Battista N, Scheggi S, Gambarana C. PPAR-α activation in a model of autism modulates social reward and endocannabinoid signaling selectively in male rats. Neuropharmacology. 2026; 296: 110996.

Social difficulties in autism spectrum disorder (ASD), including reduced sensitivity and responsiveness to the rewarding value of social stimuli (social anhedonia), may arise from dysregulation of dopaminergic and endocannabinoid (eCB) pathways. We examined whether social reward processing was restored in male and female rats prenatally exposed to valproic acid (VPA) by PPARαs activation which modulates dopaminergic and eCB transmission. After 4-week administration of the PPARα agonist fenofibrate (FBR), social interaction and social reward sensitivity were assessed, and levels of eCBs and related markers measured in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). In VPA-exposed male rats, FBR administration reinstated social behavior, increased N-palmitoyl ethanolamine (PEA) levels in the NAc and normalized fatty-acid amide hydrolase (FAAH) levels in the NAc and mPFC. In contrast, VPA-exposed female rats showed very subtle ASD-like social deficits, different patterns of eCB alterations, with decreased N-oleoyl ethanolamine (OEA) levels in both regions, and divergent responses to FBR. Overall, these findings suggest that FBR modulation of the eCB system contribute to improving social behavior in VPA-exposed male rats. Moreover, differences in eCB signaling in male and female rats may play a role in the development of sex-divergent phenotype following prenatal VPA exposure.

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24. Sánchez-García I, Sánchez-Quesada C. Does Omega-3 Help After All in Autism Spectrum Disorder? An Update Systematic Review and Meta-Analysis of Randomized Trials. Nutrients. 2026; 18(17).

BACKGROUND/OBJECTIVES: Autism Spectrum Disorder (ASD) affects approximately 60 × 10(4) incident cases, 283.3 × 10(5) prevalent cases, and 43.1 × 10(5) DALYs globally and is frequently accompanied by irritability, hyperactivity, and social withdrawal linked to low-grade neuroinflammation. Omega-3 supplementation is among the most common complementary approaches used by families, but clinical evidence remains inconsistent, and prior meta-analyses have relied on a single outcome instrument. This study aimed to evaluate the efficacy of omega-3 supplementation on ASD-associated behavioral symptoms by harmonizing outcomes across multiple validated instruments. METHODS: Twelve randomized controlled trials (number of studies per domain: k = 6-12) were identified through a systematic search of ten databases (CRD420261390092). Outcomes from eight instruments (ABC, CGI-I, BASC-2, SRS/SRS-2, GARS-2, CARS/SDQ, VABS/PLS-4/PDDBI, and CBCL) were mapped onto five behavioral domains: Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech/Communication. Random-effects models (REML, Knapp-Hartung adjustment) pooled Hedges’ g for each domain, with fixed-effects, subgroup, and PET-PEESE publication-bias sensitivity analyses. RESULTS: Significant pooled effects favoring omega-3 supplementation were observed for Irritability (g = -0.287, 95% CI [-0.562, -0.013], p = 0.043) and Inappropriate Speech/Communication (g = -0.213, 95% CI [-0.363, -0.063], p = 0.010). Lethargy/Social Withdrawal, Stereotypy, and Hyperactivity showed trivial-to-small, non-significant effects. Heterogeneity was negligible (I(2) ≤ 0.83%) in four domains; Hyperactivity showed moderate heterogeneity (I(2) = 37.86%). Sensitivity analyses confirmed robustness, and no evidence of publication bias was detected. CONCLUSIONS: Expanding synthesis beyond a single outcome instrument revealed statistically significant, though clinically modest, benefits of omega-3 supplementation on irritability and communication symptoms in ASD, effects undetectable in prior smaller, single-instrument analyses. These findings support its consideration as a low-risk adjunctive option, while larger, adequately powered trials remain needed to confirm clinical relevance.

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25. Santra R, Pulukuri SV, Sharma N. Inequities in Preventive Care for Adults with Intellectual and/or Developmental Disability in the USA: A Narrative Review. J Gen Intern Med. 2026.

A primary care physician cares for two female siblings in their 40s – one with Down syndrome, and one without. The sister without Down syndrome receives her Pap smears scheduled in accordance with national guidance. Meanwhile, this screening is repeatedly deferred for the sister with Down syndrome due to the assumption that she could not easily tolerate the exam. Concerned about her cervical cancer risk, the patient’s sister takes her to a gynecological clinic that specializes in serving those with disabilities. Utilizing simple accommodations such as picture-based explanations and thoughtful anxiolytic administration, her sister was able to get her first Pap smear two decades later than recommended. The samples, fortunately, were negative for HPV and cervical dysplasia. This real-life example on the patient level demonstrates a problem widespread on the population level: the inequitable administration and uptake of preventive care in individuals with intellectual and/or developmental disabilities (IDD). Studies have shown that these patients receive primary and secondary prevention methods such as vaccines and cancer screenings for breast, cervical, and colon cancer, at lower rates than the general population. Yet their need for this care is the same, if not higher -these patients are diagnosed at later stages and suffer higher mortality rates for these malignancies. In this narrative review, we examine disparities in preventive care utilization for US adults with IDD and describe barriers on the patient, clinician, and system levels. We then explore potential strategies to expand access, including alternative screening modalities and models of care delivery. Recognizing and addressing modifiable barriers to this care are essential to addressing preventable morbidity and mortality in this population.

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26. Serbaya SH, Surbaya SH, Hafiz TA, Khatib Sambas MFM, Alshahrani KMS. An in-silico comparative cross-sectional diagnostic- accuracy study evaluating artificial intelligence platforms in identifying autism spectrum disorder from standardized pediatric case vignettes 2026. Front Psychiatry. 2026; 17: 1941175.

BACKGROUND AND OBJECTIVE: This study evaluates the capability of various general-purpose and healthcare-specialized Artificial Intelligence (AI) platforms in identifying Autism Spectrum Disorder (ASD) from clinical narratives. METHODS: Using twenty standardized pediatric case reports (10 ASD and 10 non-ASD), the evaluation assessed diagnostic accuracy, concordance with clinical diagnoses, and statistical performance across different AI architectures. RESULTS: The platforms demonstrated diverse operational profiles; Gemini 3 Pro achieved the highest rates of sensitivity and specificity, while other evaluated models exhibited sensitivity rates ranging from 60% to 90%. While statistical differences in performance between general-purpose and specialized systems were not significant (P> 0.799), advanced large language models showed the ability to reason through complex diagnostic narratives. CONCLUSION: These findings suggest that advanced general-purpose AI platforms can offer valuable support in interpreting complex ASD case narratives. To ensure clinical safety, incorporating stratified frameworks and standardized protocols remains essential. Further evaluation is required to determine the precise role of these tools.

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27. Smith JR, Bonnee M, Marler S, Lim S, Fuchs DC, Tamargo R, Baldwin I, Maley C, VanHaverbeck A, Hamilton C, Adegoke T, Xu H, Liu J, Williams ZJ, Wilson JE, Luccarelli J. Catatonic Features That May Be Mistaken for Worsening Autism Show Treatment-Associated Improvement: Implications for Later Regression. medRxiv. 2026.

Catatonia in autistic individuals may resemble worsening autism yet represent a potentially treatable departure from baseline functioning. We compared item-level catatonic signs in autistic and non-autistic patients and evaluated treatment-associated change during electroconvulsive therapy (ECT). This single-center observational cohort included patients with catatonia who received ECT from May 2022 through April 2026. The 23-item Bush-Francis Catatonia Rating Scale (BFCRS) was assessed longitudinally. Pretreatment BFCRS data were available for 104 patients, including 41 autistic and 63 non-autistic patients, with 993 near-complete repeated assessments available. Pretreatment item presence was modeled using a three-level clinical-group variable with adjustment for age, biologic sex, and calendar year. Compared with non-autistic patients, patients with autism and intellectual disability had higher adjusted odds of eight activated, repetitive, or behaviorally dysregulated signs and lower odds of immobility/stupor. Among 96 patients with paired first and last eligible BFCRS assessments, multiple items improved in both cohorts. Generalized estimating equations demonstrated longitudinal declines in total BFCRS scores and multiple psychomotor-domain scores, with no clinical-group-by-time interaction surviving false-discovery rate correction in unrestricted or 30-, 60-, 90-, and 180-day models. Autism-specific Kanner analyses identified significant fixed-endpoint improvement in seven severity items after false-discovery rate correction, six of which were reproduced longitudinally. Catatonia in autistic patients with intellectual disability was characterized by a phenotype that may resemble worsening autism during later regression, and many constituent signs demonstrated treatment-associated improvement during ECT.

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28. Tebartz van Elst L. The SPC model as a heuristic tool to better understand autism spectrum disorder and other structural diagnosis in psychiatry and psychotherapy. Front Psychiatry. 2026; 17: 1805806.

Both autism and the broader autism phenotype represent stable mental features over time that often lead to typical psychosocial problem patterns such as bullying, interpersonal conflicts at work and at home, or social withdrawal. These patterns may in turn cause specific temporary medical conditions such as states of tension, agitation, mutism, depression, or psychosis. When presenting to psychiatry or psychotherapy patients generally do not complain about autism, but rather about depression, interpersonal conflicts, and psychosocial difficulties. They may also complain about maladaptive behaviors such as social withdrawal, gaming etc. They often have difficulty understanding themselves, generating a clear sense of self and identity, and understanding other people’s behaviors. The SPC model presented here is a heuristic tool to provide clarity on this complex interplay of different ontological entities. The model analyses life phenomena and developments according to their degree of situational freedom and modifiability. Mental structures are considered to be fateful, fundamental physical phenomena, similar to body height, IQ, and ametropia. Problems and problematic behaviors are not core phenomena of the autistic structure, despite developing in typical psychosocial dynamics and patterns in the biographies of autistic individuals. Examples include bullying, social withdrawal, and dysfunctional communication patterns. Unlike autistic structures, these should not be accepted, but changed. Conditions are understood as specific psychobiological and physical states. Affected persons are not free to intentionally alter such conditions. Unlike bodily structures, they have a beginning and an end, and are transient by nature. Examples include states of tension, depressive episodes and psychotic states. Such conditions should be treated with all available medical and psychotherapeutic means, or endured until they naturally pass. In individual situations, people are not free with respect to their own structure and biological conditions. They cannot manipulate these phenomena voluntarily. They can only compensate or cope. Problems and problem behaviors, however, can and should be solved. These phenomena fall within the realms of freedom and responsibility. Such a comprehensive understanding of one’s own body, mental structure, and psychodynamic mechanisms, as well as the typically evolving interpersonal dynamics, is of utmost importance for the development of a valid and functional self, particularly in autism.

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29. Ünözkan H, Sarıkaya HA. A hybrid deep learning framework for early autism screening. Prim Health Care Res Dev. 2026; 27: e101.

OBJECTIVES: Early diagnosis of autism spectrum disorder (ASD) remains a significant challenge due to the time-consuming and subjective nature of traditional diagnostic methods. This study proposes a reliability-oriented hybrid deep learning framework that provides a low-cost, scalable, non-invasive, and AI-assisted pre-screening tool for early ASD risk indication and referral support. METHODS: The proposed system integrates two independent deep learning architectures: (1) a ResNet18 model optimized with 10-fold cross-validation using static periocular image data, and (2) a multi-CNN facial image classification ensemble combining ResNet50, EfficientNet-B0, and DenseNet121 architectures. The periocular pathway uses the fine-tuned ResNet18 fully connected softmax layer as its decision boundary. The facial pathway uses weighted probabilistic averaging, and the two subsystem outputs are subsequently combined through an OR-based reliability fusion rule. Additionally, explainable artificial intelligence (Grad-CAM) was employed to visualize decision-relevant regions. RESULTS: The static periocular ResNet18 model achieved a sensitivity of 90%, while the multi-CNN facial classification ensemble reached a sensitivity of 87.1% and an AUC of 0.948. Under the conditional-independence assumption, OR-based reliability fusion yielded an analytically estimated system-level sensitivity of 0.9871, corresponding to a joint false-negative probability of approximately 1.29%. CONCLUSIONS: The developed hybrid model is positioned as an AI-assisted pre-screening and early-referral support tool, not as a replacement for clinical evaluation. By combining reliability-oriented parallel fusion with explainable AI, the system supports clinical transparency and offers a scalable pathway for early ASD risk indication.

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30. Unruh KE, Mosconi MW. Reward processing differences in autism: Current understandings and future directions. Soc Cogn Affect Neurosci. 2026.

Differences in reward processing repeatedly have been implicated in autism. Still, the contexts in which these differences occur (e.g., social and non-social) and the extent to which they relate to autistic traits remain poorly understood. Notably, current frameworks for reward processing have yet to describe the impacts of reward processing differences on broader cognitive domains in autism. Evidence from studies of neurotypical individuals and non-human primates shows that reward has significant impacts on multiple cognitive domains, including executive control processes that have been linked to core social communication and repetitive behavior traits in autism. These findings suggest that examining reward processes in relation to cognitive functions in autism may provide important insights into neural systems that contribute to multiple developmental abilities and psychiatric features common to autism. In this review, we present a new, testable model that describes how interactions between reward and cognitive domains may have additive or synergistic contributions to key clinical traits in autism. This model is framed in context of existing evidence for reward processing differences in autism and their relationship to clinical features, as well as broader implications for expanding existing reward-based frameworks in this population.

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31. Wei L, Chen W, Lin Y, Li C, Ran G, Liu L, Li Z, Song A, Lan L, Huang X, Chen G, Zeng X, Wang L. Joint effects of multi-metal exposure on Autism Spectrum Disorder: Associations, related genes, and biological pathways. Ecotoxicol Environ Saf. 2026; 323: 120625.

Autism Spectrum Disorder (ASD) is a common, multifactorial neurodevelopmental disorder with complex etiology. Aberrant metal exposure has been linked to ASD pathogenesis, but the independent and joint effects of multi-metal exposure remain unclear. This study investigated the associations between metal exposure and ASD in a case-control study involving 214 children aged 3-8 years, with 112 ASD cases and 102 controls. Plasma concentrations of 15 metals were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Logistic regression and restricted cubic spline models (RCS) were used to assess the associations between metals and ASD. The results indicated that higher plasma concentrations of lead (Pb) were independently associated with ASD, whereas selenium (Se) showed an inverse association. These findings were further supported by sensitivity analyses using Firth logistic regression and bootstrap resampling. Bayesian kernel machine regression (BKMR) and quantile g-computation (Qgcomp) models revealed that the joint effect of Pb and nickel (Ni) on ASD was attenuated when Se was included in the analysis. In addition, analysis of public data identified nine candidate genes potentially related to both metal exposure and ASD. RT-qPCR analysis of local samples confirmed the differential expression of the candidate genes, which were functionally linked to neurodevelopment-related pathways, including thyroid hormone signaling, mTOR/AMPK signaling, and synaptic plasticity. Overall, this study suggests that specific plasma metal profiles may be associated with ASD and highlights the potential relevance of considering multi-metal exposure patterns. Further longitudinal studies and experimental investigations are required to determine the temporal relationship and potential biological mechanisms linking metal exposure to ASD. LAY SUMMARY: Autism Spectrum Disorder is thought to involve both genetic and environmental factors. In this case-control study, we measured multiple metals in children’s plasma and found that children with ASD had different metal profiles compared with controls, particularly for lead, nickel, and selenium. When metals were considered together, selenium appeared to influence the observed associations involving lead and nickel. We also identified several genes that may be related to both metal exposure and neurodevelopmental processes. These findings suggest that metal exposure patterns may be relevant to ASD, but larger longitudinal and mechanistic studies are needed to clarify these relationships.

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32. Yang G, Gong C, Zheng X, Chen H, Wang Y, Zhang H, Hu F, Wan J, Zhu Z, Sun X, Zhang L, Li R. Early-life exposure to polypropylene microplastics and DEHP induces ASD-relevant neurodevelopmental alterations involving mTOR-regulated autophagy impairment. Ecotoxicol Environ Saf. 2026; 323: 120659.

The health risks of polypropylene plastic, a major food-grade polymer, are often underestimated. Current evidence indicates that infants and young children may ingest millions of polypropylene microplastic particles (PP-MPs) daily, accompanied by co-exposure to di(2-ethylhexyl) phthalate (DEHP). However, the neurotoxic effects of such co-exposure, particularly the underlying molecular mechanisms, remain poorly understood. Here, we established an early-life exposure model by orally administering PP-MPs and/or DEHP to 3-week-old male ICR mice for 28 consecutive days. Based on assessments of neurobehavior, histopathology and representative biomarkers, we found that PP-MPs and/or DEHP exposure caused autism spectrum disorder (ASD)-relevant neurodevelopmental alterations in immature mice, including deficits in spontaneous exploration and social interaction, increased anxiety-like behaviors, neuronal and synaptic damage in the prefrontal cortex, and downregulated expression of the ASD-risk genes Shank3 and Nlgn1. Proteomic analyses of the brain identified the mTOR signaling pathway as a key mechanism involved in the ASD-relevant neurodevelopmental alterations resulting from PP-MPs and/or DEHP exposure. Further quantitative analyses demonstrated activation of the mTOR signaling pathway, coupled with autophagic impairment and dysregulated expression of genes linked to synaptic plasticity following exposure. Notably, inhibiting the mTOR signaling pathway with rapamycin restored autophagic activity and ameliorated the ASD-relevant neurodevelopmental alterations induced by PP-MPs and/or DEHP. Collectively, these findings suggest that mTOR-regulated autophagic impairment may underlie the neurodevelopmental toxicity caused by early-life exposure to PP-MPs and DEHP, providing a theoretical basis for risk assessment and health protection strategies against neurodevelopmental hazards posed by plastic consumer products during early life.

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33. Zaikin A, Vlasenko D, Zakharov D, Oganezova JG, Krivonosov MI, Ivanchenko M, Blyuss O. Benchmarking Synolitic Graphs for Autism Classification from Multisite Resting-State fMRI. Diagnostics (Basel). 2026; 16(17).

Background/Objectives: Synolitic graphs (SGs) were developed for task-based fMRI, where edge weights encode the discriminative power of pairwise regional features; whether similar information can be recovered from resting-state data was untested. We benchmarked SGs for autism spectrum disorder (ASD) classification using the multisite ABIDE-I dataset (871 subjects: 403 subjects with ASD, 468 typical controls; 17 sites; CC200 atlas). Methods: Using 5-fold cross-validation with 10 repeats and balanced accuracy as the primary metric, we compared SGs with eight baselines including correlation matrices, tangent space connectivity, elastic net logistic regression, SVM, and XGBoost. Results: The vectorised correlation matrix achieved 67.9% balanced accuracy (AUC = 0.743), the combined model 68.0% (AUC = 0.744), and SGs 57.0% (AUC = 0.598). SGs performed above chance (permutation p = 0.001), but their performance was not significantly different from that of direct logistic regression (Nadeau-Bengio p = 0.82). After covariate residualisation, correlation-based methods retained 66.9-67.1% balanced accuracy, while SGs achieved 55.6%. Leave-one-site-out validation yielded 66.0-66.2% for correlation-based models and 55.0% for SGs, with similar declines of approximately 2 percentage points from standard cross-validation. SG-derived ROI rankings were unstable, and ADOS severity prediction among 193 ASD participants was underpowered and inconclusive. Conclusions: Conventional connectivity representations substantially outperformed SGs for resting-state ASD classification, contrasting with previously reported task-fMRI advantages. No evaluated method achieved performance suitable for stand-alone clinical screening or diagnosis; this study should therefore be interpreted as a methodological benchmark rather than a validation of a clinically deployable tool.

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34. Zhao S, Wang J, Pan Y, Yang Y, Yin Y, Li W, Li J, Feng X. Sex differences in ferroptosis-related vulnerability to autism-like deficits in the adolescent medial prefrontal cortex following embryonic valproic acid exposure. Biol Sex Differ. 2026; 17(1).

BACKGROUND: Prenatal valproic acid (VPA) exposure is an important environmental risk factor for autism spectrum disorder (ASD), but the mechanisms underlying VPA-induced ASD-like phenotypes remain unclear. Emerging evidence implicates neuronal ferroptosis and neurodevelopmental disturbances, yet whether these alterations vary across developmental stages and between sexes is unknown. METHODS: Adolescent male and female C57BL/6 mice exposed to VPA at embryonic day 12.5 (E12.5) or postnatal day 14 (PND14) were used to examine behavioral and neurobiological effects of VPA exposure across developmental stages and between sexes. Sociability and anxiety-like behaviors were assessed using the three-chamber social interaction test (3-CT) and open field test (OFT), respectively. Histological alterations in the medial prefrontal cortex (mPFC), hippocampus, and striatum were examined using hematoxylin-eosin (HE) and Nissl staining. Ferroptosis-related changes were evaluated using biochemical assays, immunofluorescence, transmission electron microscopy and Western blotting. In male mice, the effects of prenatal and early postnatal VPA exposure were compared to assess whether similar behavioral and ferroptosis-related alterations were observed across developmental windows. RESULTS: Both male and female adolescent offspring exposed to VPA exhibited social deficits and anxiety-like behaviors, with a more pronounced behavioral deficits in males, particularly in social preference and sociability. Histological analysis revealed variable degrees of neuronal abnormalities in the mPFC and hippocampus of VPA-exposed offspring, with the most prominent alterations observed in the mPFC. These histological changes were observed in both male and female offspring. Ferroptosis-related molecular changes were most evident in the mPFC and were accompanied by mitochondrial abnormalities and vacuolization. These alterations exhibited a distinct pattern of sex differences, with more pronounced changes observed in males than in females. Additionally, in male offspring, prenatal and early postnatal VPA exposure were associated with similar patterns of behavioral abnormalities and ferroptosis-related changes in the mPFC. CONCLUSION: This study suggests that prenatal VPA exposure induces ferroptosis-related abnormalities which could be linked to ASD-like behavioral and functional impairments, with more pronounced changes observed in male offspring. Among the brain regions examined, the mPFC showed the most prominent neurohistological and ferroptosis-related alterations. In male mice, prenatal and early postnatal VPA exposure were associated with similar patterns of ferroptosis-related molecular alterations, suggesting that ferroptosis-assiociated alterations may represent a shared molecular feature of VPA-induced neurodevelopmental abnormalities across different developmental windows. Autism is diagnosed more often in boys than in girls, but the biological reasons for this sex difference remain unclear. Valproic acid (VPA) is used to treat epilepsy and certain mood disorders, although prenatal exposure has been associated with an increased risk of autism-related developmental impairments. In our study, we explored whether VPA affects the developing brain differently in male and female mice. We used a well-established mouse model in which animals were exposed to VPA before birth. When the mice reached adolescence, we examined their social behavior, activity, and anxiety-like behavior. We also looked at several brain areas, including the medial prefrontal cortex (mPFC), which has been implicated in social behavior, emotional processing, and decision-making. We then compared male mice exposed to VPA before birth with male mice exposed during early life. Our findings showed that VPA exposure reduced social behavior and increased anxiety-like behavior in both male and female mice, with sex-related differences in the magnitude of these behavioral alterations. The clearest brain changes were found in the mPFC, where neuronal alterations were observed in both male and female mice. We also found signs of iron-related cell stress, known as ferroptosis, particularly in the mPFC. Similar patterns of behavioral and ferroptosis-related changes were observed in male mice following exposure before birth or during early life. Overall, our findings suggest that ferroptosis-related changes in the mPFC are associated with the more pronounced autism-like behavioral changes observed in male mice following VPA exposure. eng.

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