1. Abdelmoneim Z, Eltaher H, Hussein MA, Hashish ME. Neurodevelopmental assessment of early treated children with phenylketonuria: insights from Griffith III scales. Eur J Pediatr. 2025; 184(9): 554.

Neonatal screening of phenylketonuria (PKU) and early treatment are fundamental to prevent mental retardation in children. Unfortunately, it has been observed that some neurological sequelae may still be exhibited despite these preventive strategies. Assessment of the neurodevelopment of early treated children may aid in understanding the devastating effect of PKU on the developing brain, so this study aimed to investigate the neurodevelopmental outcome of early-treated children with PKU using Griffiths-III developmental scales. We conducted an observational single-center case-control study on a total of 60 children. We compared the neurodevelopmental profile of two groups of children (PKU group = 30 and healthy control group = 30) using Griffiths-III developmental scales. Also PKU children were divided into two subgroups according to their phenylalanine level: controlled and uncontrolled. There were significant decreases in the mean of developmental quotients (DQs) of Griffiths-III subscales A, B, C, D, and general development of PKU group. While there was insignificant difference in the DQ of subscale E (gross motor) among the two groups, there was a significant difference between the two PKU subgroups regarding the developmental quotient of subscales A, B, C, E, and general development. Also, there was a statistically significant correlation between phenylalanine (Phe) levels and the mean of DQs of all Griffiths-III subscales. CONCLUSION: Early- treated PKU children are at risk of poor neurodevelopmental outcome even if their gross motor function is normal and this defect is negatively correlated with phenylalanine levels. WHAT IS KNOWN: • PKU is an inborn error of metabolism that causes mental retardation if not treated early. • Neonatal screening and early treatment prevent mental retardation. WHAT IS NEW: • Despite neonatal screening and early treatment, PKU children still exhibit mental function impairment. • The Griffiths III developmental scales is the first time to be used to assess mental functions in PKU children.

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2. Aitken D, Hodge G, Page M, Lastmann E, Hiller S, George RE. Correction: Navigating medical school with autism: a systematic review exploring student experiences & support provision in the United Kingdom. BMC Med Educ. 2025; 25(1): 1166.

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3. Altozano A, Minissi ME, Gomez-Zaragoza L, Maddalon L, Alcaniz M, Marin-Morales J. Enhancing Psychological Assessments with Open-Ended Questionnaires and Large Language Models: An ASD Case Study. IEEE J Biomed Health Inform. 2025; Pp.

Open-ended questionnaires allow respondents to express freely, capturing richer information than close-ended formats, but they are harder to analyze. Recent natural language processing advancements enable automatic assessment of open-ended responses, yet its use in psychological classification is underexplored. This study proposes a methodology using pre-trained large language models (LLMs) for automatic classification of open-ended questionnaires, applied to autism spectrum disorder (ASD) classification via parental reports. We compare multiple training strategies using transcribed responses from 51 parents (26 with typically developing children, 25 with ASD), exploring variations in model fine-tuning, input representation, and specificity. Subject-level predictions are derived by aggregating 12 individual question responses. Our best approach achieved 84% subject-wise accuracy and 1.0 ROC-AUC using an OpenAI embedding model, per-question training, including questions in the input, and combining the predictions with a voting system. In addition, a zero-shot evaluation using GPT-4o was conducted, yielding comparable results, underscoring the potential of both compact, local models and large out-of-the-box LLMs. To enhance transparency, we explored interpretability methods. Proprietary LLMs like GPT-4o offered no direct explanation, and OpenAI embedding models showed limited interpretability. However, locally deployable LLMs provided the highest interpretability. This highlights a trade-off between proprietary models’ performance and local models’ explainability. Our findings validate LLMs for automatically classifying open-ended questionnaires, offering a scalable, cost-effective complement for ASD assessment. These results suggest broader applicability for psychological analysis of other conditions, advancing LLM use in mental health research.

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4. Chuang YC, Huang YJ, Lai MC, Su SS, Kuo CJ. Incidence of Physical Health Conditions in Autistic Children Within 5 Years After Their Autism Diagnosis. Autism Res. 2025.

This study aimed to investigate the incidence of physical illnesses of autistic young children compared with children in the general population. This population-based study included children (aged ≤ 5 years) with newly diagnosed autism (autism group), followed up for 5 years after their autism diagnoses. Data were collected from Taiwan’s National Health Insurance Research Database in the period of 2000-2019. Autistic children (n = 45,680) were matched (1:20; by age and sex [assigned at birth]) with a comparison group from the general population (n = 913,600). We calculated incidence rate ratios (IRRs) for physical illnesses diagnosed within 5 years after autism diagnoses. Data were analyzed using Poisson regression models adjusted for person-time and stratified by sex and the presence/absence of intellectual disabilities. The prevalence of almost all illnesses across major organ systems after 1 year of autism diagnosis was higher in the autism group than in the comparison group. The autism group exhibited significantly elevated incidence of cardiovascular disorders, cerebrovascular disorders, and endocrine diseases within 1 year after autism diagnosis (IRR 2.30-71.42). Although the incidence rates of these illnesses decreased over the 5-year follow-up period in the autism group, they remained higher than those in the comparison group, with most IRRs exceeding 2 in the fifth year after autism diagnosis. The IRRs were significant in both autistic male and female children and those with and without intellectual disabilities, although those with intellectual disabilities displayed descriptively larger IRRs. Autistic young children have heightened risks of being diagnosed with physical illnesses soon after their autism diagnoses. Future research should understand the etiological associations between autism and physical illnesses to offer tailored care from early in life.

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5. Issa F, Yerna X, Parpaite T, Jabbour C, Schakman O, Tajeddine N, Gualdani R, Gailly P. Conditional deletion of TRPC1 channel modulates synaptic plasticity, long term depression, and memory extinction in Fragile X syndrome mice. iScience. 2025; 28(8): 113085.

Group I metabotropic glutamate receptors (mGluRs), particularly mGluR5, regulate synaptic plasticity via long-term depression (mGluR-LTD), a process implicated in declarative memory. We previously identified TRPC1, a highly expressed hippocampal ion channel, as a key mGluR5 effector. Using a Cre-tamoxifen system, we acutely deleted Trpc1 in a Fragile X syndrome (FXS) mouse model, characterized by mGluR5 hyperactivity, enhanced mGluR-LTD, and social deficits. In FXS neurons, mGluR5-evoked currents were elevated and normalized by Trpc1 deletion. This deletion also improved social behavior and reduced anxiety. Notably, it abolished mGluR-LTD and normalized memory extinction, as shown in behavioral assays. Mechanistically, mGluR5 activation induced ARC protein expression via eEF2K- and ERK1/2-dependent pathways, modulating Arc translation and transcription. These findings highlight TRPC1 as a crucial mediator of pathological plasticity in FXS and a potential therapeutic target.

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6. Li M, Wang S, Chang L, Chen R, Liu Y, Ye Z, Zhao Y, Ma Y, Yang J, Gan X, Zhuang Y, Wang P. Mn(3)O(4) nanozymes as potential therapeutic agents for autism spectrum disorder: insights from behavioral and molecular studies. Nanoscale. 2025.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder of uncertain etiology. Current studies suggest that ASD progression is closely linked to an imbalance between oxidative stress and antioxidant capacity, marked by elevated levels of reactive oxygen species (ROS) and reduced concentrations of antioxidant molecules such as superoxide dismutase (SOD) and glutathione (GSH). Although the human body does possess endogenous ROS-scavenging enzymes, their sensitivity to environmental conditions and the difficulties of large-scale production limit their practical application. Consequently, substantial efforts have been dedicated in recent years to developing artificial enzymes with ROS-scavenging activity. Among these, ROS-scavenging nanozymes have been widely used due to their enhanced stability and multifunctionality. Notably, only a few manganese-containing nanozymes have been reported to exhibit effective reactive oxygen species (ROS) scavenging activity thus far. Methods: In this study, we utilized Mn(3)O(4) nanozymes (Mn(3)O(4) NZs) exhibiting superoxide dismutase, catalase, and hydroxyl radical-scavenging activities. We assessed brain injury, as well as the antioxidative and anti-inflammatory effects of Mn(3)O(4) NZs through behavioral tests, Nissl staining, immunofluorescence assays, and a laser speckle imaging system. Furthermore, we explored the underlying mechanisms of Mn(3)O(4) NZs by employing ELISA kits, oxidative stress detection kits, and immunofluorescence analysis. Results: The results demonstrated that Mn(3)O(4) NZs increase cerebral blood flow and effectively ameliorate ischemic and hypoxic conditions in BTBR mice. Moreover, they improve social deficits, repetitive stereotyped behaviors, cognitive impairment, and neuronal morphological damage. Further in vitro experiments confirmed that Mn(3)O(4) NZs exert neuroprotective effects in BTBR mice by mitigating oxidative stress and inflammation. Conclusion: These findings indicate that Mn(3)O(4) NZs exhibit excellent antioxidant and anti-inflammatory effects in vitro and effectively enhance cerebral blood flow, ameliorate behavioral deficits, and alleviate neuronal damage in BTBR mice in vivo. Collectively, our results suggest that Mn(3)O(4) NZs exert neuroprotective effects in the hippocampus of BTBR mice by reducing oxidative stress, mitigating neuroinflammation, and rescuing neuronal injury. Consequently, they hold promise as a potential nanomaterial for the treatment of autism.

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7. Murray DS, Anixt JS, Vasudevan V, Cole LL, Fedele A, Karpur A, Cornell WL, Latten LM, Butter EM, Coury DL. Preferences for Outcome Data Collection and Access in a Pediatric Autism Learning Health Network Registry. J Dev Behav Pediatr. 2025.

OBJECTIVE: Health professionals participating in learning health networks collect data for informing clinical decision-making, research, and quality improvement (QI). To optimize the collection and use of clinical and Parent Reported Outcome (PRO) data for these purposes, it is important to understand the priorities of patient registry « end users » (clinicians, researchers, and patients/families). METHODS: The analysis used a sequential mixed-methods approach with parent (n = 93) and clinician (n = 167) surveys followed by targeted interviews (parent n = 9, clinician/researcher n = 7) completed at Autism Care Network (ACNet) sites to better understand current use of registry data and parent/clinician priorities. RESULTS: Sixty percent of parents reported receiving behavioral data regarding their child from their health provider in the past, and 90% felt these data would help them understand their child’s behavior. Among data access options parents preferred an online portal (72%) and/or the clinic’s electronic medical record (59%). Parents indicated willingness to complete surveys longitudinally if the assessments correlated with their child’s specific areas of difficulty. Priorities for clinicians included easy access to the data (84%), meaningful connection to clinical outcomes (81%), and measures that can demonstrate change in symptoms over time (76%) and that are easy for families to complete (80%). Both groups recommend assessing parenting stress and social determinants of health. CONCLUSION: Consideration of end-user priorities can improve patient registry data collection, analysis, and utilization. Families may be more willing to participate if they can receive direct benefit by accessing their own data and clinicians use this data to optimize clinical care.

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8. Palanivelu L, Chen YY, Liang YW, Li SJ, Chang CW, Huang YT, Lo YC. Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats. Neuroimage. 2025; 317: 121344.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by abnormalities in brain microstructure, neuroinflammation, and social behavior deficits. In addition, children with ASD frequently exhibit irritable bowel syndrome and other gastrointestinal symptoms linked to anxiety. This study investigated if central thalamic nucleus deep brain stimulation (CTN-DBS) can improve social behavior, suppress neuroinflammation, restore brain microstructure, and reverse gut dysbiosis in the valproic acid-induced rat model of ASD by modulating the microbiota-gut-brain (MGB) axis. Daily CTN-DBS for 7 days (30 min/day) enhanced neuronal density, organization, and microstructural complexity as evidenced by increases in the diffusion kurtosis imaging (DKI) metrics-mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK). These neurostructural improvements were associated with reduced astrocyte and microglial activation, two core hallmarks of neuroinflammation in ASD, and lower systemic levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, signaling factors that may increase gut permeability and disrupt gut microbial composition. Indeed, CTN-DBS enhanced gut barrier function, promoted the proliferation of beneficial Bacteroides spp., and improved short-chain fatty acid (SCFA) metabolism, thereby restoring normal gut acetate and butyrate levels and counteracting dysbiosis. Specific energy absorption rate and thermal effect analyses demonstrated that CTN-DBS is safe under DKI. These findings support CTN-DBS as a safe and efficacious therapeutic strategy to reduce neuroinflammation, restore gray matter circuit function, and improve gut microbial composition in ASD via MGB axis modulation. Furthermore, DKI can reveal neurobiomarkers indicative of these improvements in ASD model rats.

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9. Saeed S, Siegert AM, Tung YCL, Khanam R, Janjua QM, Manzoor J, Derhourhi M, Toussaint B, Lam BY, Mahmoud SA, Vaillant E, Buse Falay E, Amanzougarene S, Ayesha H, Khan WI, Ramazan N, Saudek V, O’Rahilly S, Goldstone AP, Arslan M, Bonnefond A, Froguel P, Yeo GS. Biallelic variants in SREK1 downregulating SNORD115 and SNORD116 cause a Prader-Willi-like syndrome. J Clin Invest. 2025; 135(16).

Biallelic variations in SREK1 reduce SNORD115/116 expression, linking severe obesity and Prader-Willi-like traits, offering genetic and molecular insights into a new form of syndromic obesity.

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10. Schaaf RC, Ridgway EM, Jones EA, Dumont RL, Foxe J, Conly T, Sancimino C, Yi M, Mailloux Z, Hunt JM, Kirschner L, Leiby BE, Molholm S. A Comparative Trial of Occupational Therapy Using Ayres Sensory Integration and Applied Behavior Analysis Interventions for Autistic Children. Autism Res. 2025.

Many autistic children demonstrate sensory integration differences that impact their participation in daily living activities and tasks. Occupational Therapy using Ayres Sensory Integration (OT-ASI) is an evidence-based intervention for autistic children that addresses the sensory integrative factors impacting daily living skills and participation in a variety of tasks and activities. Applied Behavior Analysis (ABA) is the recommended evidence-based practice for autism to improve a range of developmental domains. This study compared Occupational Therapy using Ayres Sensory Integration, Applied Behavior Analysis, and no treatment on daily living skills and individualized goals for autistic children who also show sensory differences. A parallel arm comparative effectiveness trial design with participants randomized equally to OT-ASI, ABA, or no treatment. Intervention consisted of 30 one-hour sessions. Significant gains in individualized goals, measured by Goal Attainment Scaling, were found in both treatment arms over the no treatment group. Both the OT-ASI and the ABA groups improved in daily living skills measured on the Pediatric Evaluation of Disabilities Inventory; although the improvements over the no treatment group were not significant. Both OT-ASI and ABA improved individualized goals and daily living skills at comparable levels. These findings are discussed in light of their implications for intervention. Trial Registration: NCT02536365.

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11. Su L, Liu T, Wei L. The influence of sound on joint attention in individuals with high autistic traits: Evidence from eye movements and fNIRS. Acta Psychol (Amst). 2025; 259: 105365.

BACKGROUND: Individuals with subclinical autistic traits demonstrate joint attention (JA) impairments analogous to those observed in autism spectrum disorder (ASD). This study investigated whether sound cues enhance JA performance in high Autism Spectrum Quotient (AQ) individuals and characterized the neurocognitive mechanisms underlying this modulation. METHODS: A crossover experimental design was implemented across two modalities. Experiment 1 (eye movements) included 22 high AQ and 22 low AQ subjects, while Experiment 2 (functional near-infrared spectroscopy, fNIRS) involved 28 high AQ and 19 low AQ subjects. Multimodal analyses compared gaze patterns and the activation of prefrontal-temporal cortical during sound v.s silent JA tasks. RESULTS: a) under sound JA, all subjects had longer dwell time than silent JA. b) under sound JA, low AQ had more activation of dorsolateral prefrontal than silent JA. c) under sound JA, low AQ had more activation of dorsolateral prefrontal than high AQ. d) under non-JA, the sound cues made high AQ had more activation of temporal than silent condition. CONCLUSION: Sound influences JA processing through dual-pathway mechanisms: augmenting prefrontal attentional control in low AQ while inducing compensatory temporal activation in high AQ. This neurofunctional dichotomy supports the autism trait continuum hypothesis and validates the feasibility of multimodal paradigms for simulating core ASD symptoms, laying a methodological foundation for developing novel intervention strategies.

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12. Sutherland R, Hodge MA, Boulton K, Baracz S, Brooks G, Bennett B, Ong N, Papanicolaou A, Tomsic G, Williamsz M, Guastella A, Silove N. Screen to Screen Versus Face to Face: Evaluating Telehealth Autism Diagnostic Assessments for Young Children in a Diverse Clinical Setting. Autism Res. 2025.

Access to autism diagnostic assessments continues to be problematic for many families and children. While telehealth assessments have been shown to be feasible and reliable in research settings, less is known about the agreement between telehealth autism assessments compared with in-person evaluations in clinical settings with linguistic, cultural, and social diversity. Twenty-one minimally verbal children (between 23.9 and 51.7 months, mean = 36.5 months, SD = 8 months) participated in a telehealth autism assessment (the TELE-ASD-PEDS; TAP) with a parent, and then in an in-person, multidisciplinary team assessment. Telehealth clinicians were blinded to history and questionnaire information; in-person clinicians were blinded to the telehealth results. Assessment results in each setting, along with diagnostic impression (telehealth) and diagnostic outcome (in-person), were compared. Assessment scores across the settings showed very good agreement and were strongly correlated (r = 0.75, p < 0.001). There was diagnostic agreement (either autism/autism or no-autism/no-autism) for 19/21 children, or 90% of the participants. This study adds to the growing literature on autism diagnostic assessments administered via telehealth. Our research builds on previous work by comparing telehealth findings directly with in-person assessment and diagnostic results. The results of the present study yielded high rates of diagnostic agreement as well as strong agreement between telehealth and in-person assessment scores for young children with limited language and high levels of autism symptoms, which to our knowledge, have not to date been directly compared.

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13. Wang Y, Meng K, Chen H, Jin X, Yang G, Ma G, Cheng Y, Zhao C, Zheng C, Xie M, Gao P, Wang L, Zhang W. Multiple problems: a case of Cohen syndrome VPS13B mutation causing bilateral spherical lenses combined with retinitis pigmentosa. BMC Ophthalmol. 2025; 25(1): 345.

BACKGROUND: Cohen syndrome is a rare autosomal recessive disorder characterized by facial anomalies with or without microcephaly, non-progressive intellectual disability, hypotonia, ocular abnormalities, and neutropenia. Due to its low prevalence and diverse presentations, much information about the disease, including ocular manifestations, is not yet fully understood. To date, there is a paucity of literature on Cohen syndrome, which is characterized by predominantly ocular manifestations and typical manifestations in multiple systems throughout the body. CASE PRESENTATION: A 24-year-old male with a history of intellectual disability since childhood presented with decreased vision in both eyes for 2 years. He was diagnosed with bilateral spherical lens, bilateral subluxation of lens, bilateral concurrent cataracts, and bilateral retinitis pigmentosa. Cataract extraction combined with intraocular lens implantation was successful in both eyes, and vision improved after surgery. His underlying syndrome was studied genetically by whole exome sequencing. Genetic testing through whole-exome sequencing revealed a mutation in the VPS13B gene: c.6865 + 1G > T, confirming the diagnosis of Cohen syndrome. CONCLUSION: Ophthalmologists should consider the diagnosis of Cohen syndrome in patients with developmental delay, spherical lens, and retinitis pigmentosa. A detailed ophthalmologic examination and general examination should be considered in such patients.

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14. Xie B, Ma D, Feng JW, Sun XR, Ou-Yang YQ, Xu YN. Influences of parental intimacy and self-disclosure on dyadic coping among parents raising school-aged children diagnosed with autism spectrum disorder. J Family Med Prim Care. 2025; 14(7): 2774-81.

PURPOSE: The study examined the effects of partners’ intimacy and disclosure levels on their own and their spouses’ experiences of relational uncertainty, changes in interdependence, and relational turbulence. METHODS: A total of 201 married couples parenting a child with autism spectrum disorder (ASD) who was beginning school or who had started school in the past 6 months completed three questionnaires and provided demographic information. RESULT: Only scores for parental disclosure showed no correlation (r = 0.097, P > 0.05), whereas the other variables were correlated. Only parental intimacy demonstrated a correlation (r = 0.154, P < 0.05). Parental dyadic coping was correlated with parental disclosure (mothers: r = 0.448, P < 0.01; fathers: r = 0.445, P < 0.01). The mode Actor-Partner Interdependence Model examined the effect of overall intimacy on dyadic coping and presented a qualified fit: (χ2) =76.466, comparative fit index = 0.99, and root mean square error of approximation = 0.027. The partner effect of fathers' intimacy on mothers' dyadic coping was statistically significant (B = 0.344, P < 0.001), whereas mothers' intimacy was not significantly related to fathers' dyadic coping (B = 0.64, P > 0.24). CONCLUSION: The findings indicate that parental intimacy and self-disclosure within dyadic coping influence certain relationship qualities. Furthermore, individuals’ perceptions of their spouse’s dyadic coping abilities were a stronger predictor of relational turbulence than self-reported coping. These results offer important insights into how married couples can safeguard their relationship during their child’s health-related transitions.

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15. Zhang ZH, Hu KX, Shi YC, Zhou HY. Aberrant predictive learning along the positive schizotypy – autistic traits continuum: evidence from ambiguous social information processing. Asian J Psychiatr. 2025; 111: 104666.

Deficits in social information processing have been observed in both schizophrenia spectrum disorders (SSD) and autism spectrum disorder (ASD), though the underlying mechanisms may differ. From a predictive coding perspective, such deficits are thought to arise from an overreliance on prior expectations in SSD, whereas individuals with ASD may exhibit difficulties in forming or using such expectations. However, very few studies have investigated the behavioral markers underlying social predictive learning along the ASD-SSD continuum. Using a novel cue-outcome associative learning task, this study examined how prior expectations influence the perception of ambiguous social information. A total of 121 healthy participants (aged 17-25) completed the task, along with self-report measures of positive schizotypal (Schizotypal Personality Questionnaire, SPQ; Community Assessment of Psychic Experiences, CAPE) and autistic traits (Autism Spectrum Quotient, AQ). Computational modeling using the Hierarchical Gaussian Filter (HGF) and correlational analyses revealed that higher levels of positive schizotypal traits were associated with greater reliance on prior beliefs and reduced flexibility in updating prediction errors. In contrast, expected inverse associations for autistic traits were not consistently observed. These results support the hyper-prior hypothesis of schizophrenia and highlight aberrant predictive mechanisms in positive schizotypy. The predictive coding framework might be useful for differentiating between SSD- and ASD-related social cognitive difficulties, with implications for targeted intervention strategies.

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