1. Boer J, Boonstra N, Kronenberg L, Kuipers S, Vuijk R, Sizoo B. Autistic eye contact? A hermeneutic phenomenological multicenter study of the similarities and differences in eye-contact experiences between adults with and without autism. J Neurodev Disord. 2025.

Eye contact is one of the most important forms of interpersonal communication. Nonetheless, research has shown that there is no gold standard for how eye contact should occur. Atypicalities in eye contact are one of the core features of autism spectrum disorder (ASD), but there is still no consensus on what constitutes atypical eye contact in ASD. The current research explores both the breadth and depth of experiences with eye contact in adults with and without ASD. We used a hermeneutic phenomenological multicenter design in which 15 adults with ASD and 15 adults without ASD were interviewed. Analyses using Multisite Qualitative Analysis (MSQA) and the PRICE model for saturation identified four themes: opinion on eye contact, experience of eye contact, approach toward eye contact, and needs regarding eye contact. Adults with and without ASD appeared to have overlapping and distinct experiences. This study provides the first insights into similarities and differences in experiences with eye contact in adults with and without ASD. The results provide guidance for future research and for the development of interventions to reduce problems arising from eye contact in ASD.

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2. Caron C, McCullagh EA, Bertolin G. Correction to: ‘Sex-specific loss of mitochondrial membrane integrity in the auditory brainstem of a mouse model of Fragile X Syndrome’ (2024), by Caron et al. Open Biol. 2025; 15(11): 250374.

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3. Chen G, Ishikuro M, Ohseto H, Noda A, Shinoda G, Orui M, Obara T, Kuriyama S. Child Developmental Patterns by Age 4 Years Across Subtypes of Hypertensive Disorders of Pregnancy. JAMA Netw Open. 2025; 8(11): e2545719.

IMPORTANCE: Exposure to hypertensive disorders of pregnancy (HDP) during the fetal stage has been linked to developmental delays in children. However, the associations between HDP subtypes and longitudinal patterns in child development remain unclear. OBJECTIVE: To investigate the associations of HDP subtypes with child developmental patterns. DESIGN, SETTING, AND PARTICIPANTS: This study used data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study recruiting pregnant individuals in Japan between July 2013 and March 2017. Mother-child pairs were included in the analysis. The data analysis was conducted from November 2023 to February 2024. EXPOSURES: HDP and its subtypes (gestational hypertension and preeclampsia) were identified using an algorithm applied to antenatal visit records. MAIN OUTCOMES AND MEASURES: The latent class trajectory model was applied to child development scores at ages 6, 12, 24, 42, and 48 months to generate patterns in 5 domains (communication, gross motor, fine motor, problem solving, and personal-social). Multinomial Poisson regression analysis calculated the risk ratios (RRs) of different developmental patterns by exposure to any HDP as well as HDP subtypes. A subgroup analysis was performed by preterm birth. RESULTS: Among 14 023 mother-child pairs (maternal mean [SD] age, 32.5 [4.8] years; 6754 [48.2%] female children), 1406 (10.0%) were exposed to HDP. Three patterns were identified in the 5 domains: normal, delay, and catch-up. Point estimates for delays in multiple domains of development were greater for any HDP, preeclampsia, and early-onset preeclampsia, but not all findings were statistically significant. Early-onset preeclampsia was associated with a significantly higher risk of delay pattern in problem solving domain (RR, 2.90; 95% CI, 1.43-5.89; adjusted P = .047), although the risks of delay pattern were not statistically significant in communication (RR, 1.94; 95% CI, 1.14-3.29; adjusted P = .15), gross motor (RR, 2.10; 95% CI, 1.26-3.51; adjusted P = .06), or fine motor (RR, 2.68; 95% CI, 1.26-5.71; adjusted P = .11) domains. In the term-born population, children exposed to preeclampsia and had an RR greater than 1 for the delay pattern in the problem solving domain (RR, 1.67; 95% CI, 1.92-2.74; adjusted P = .60), although this finding was not statistically significant after adjusting for multiple comparisons. CONCLUSIONS AND RELEVANCE: In this cohort study, fetal exposure to early-onset preeclampsia was associated with higher risk of a delayed child developmental pattern in the problem solving domain. The observations were modified by preterm birth. These findings suggest that children exposed to certain HDP subtypes during fetal life require developmental monitoring, especially if they were born preterm.

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4. Chen Z, Wang X, Han F. Unveiling the multitarget mechanism of Liuwei Dihuang decoction in autism spectrum disorder via network pharmacology and molecular docking. Sci Rep. 2025.

Liuwei Dihuang decoction (LW) is used for paediatric autism spectrum disorders (ASD) treatment, but its mechanism of action is unclear. This study aims to provide clinical evidence for LW in treating ASD in children and investigate its mechanism through network pharmacology, microarray analysis, and molecular docking. A retrospective review of 80 clinical cases of children with ASD and the therapeutic effect of LW was conducted. Drug-disease co-expressed genes were used to construct PPI network maps. The active ingredients of LW were obtained from the TCMSP, CNKI, and PubMed, with screening criteria of OB ≥ 30% and DL ≥ 0.18. Disease targets were sourced from the GeneCards, OMIM, and DisGeNET databases. Core targets were further analyzed using GO and KEGG. Microarray data were employed to analyze the expression levels of the core targets. Molecular docking and dynamics simulations were performed on protein-ligand complexes. MD simulations were performed using GROMACS 2022 for 100 ns, and the stability of the complex was evaluated by analyzing key parameters including RMSD, RMSF, and hydrogen bond occupancy. LW showed promising therapeutic effects on ASD, with efficacy decreasing with age. Quercetin, Tetrahydroalstonine, Diosgenin and Kaempferol were identified as active compounds. PTGS2 and MMP9 were upregulated and identified as key genes in ASD treatment. The binding energies of the key complexes PTGS2-Quercetin, PTGS2-Tetrahydroalstonine, MMP9-Diosgenin, and MMP9-Kaempferol were determined to be - 9.5 kJ/mol, - 9.4 kJ/mol, - 8.1 kJ/mol, and - 7.2 kJ/mol, respectively. Molecular simulations showed favorable binding between key genes and active compounds. This study provides clinical evidence for the treatment of ASD with LW, and predicts its main active ingredients, potential pathways, and core targets, providing a reliable basis for the clinical treatment and drug screening of ASD.

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5. Cheng X, Nareddula S, Gao HC, Chen Y, Xiao T, Nadew YY, Xu F, Edens PA, Saldarriaga V, Hu X, Quinn CJ, Kimbrough A, Huang F, Chubykin AA. Disrupted theta synchronization and synaptic connectivity in the visual cortex of Fmr1 KO mice. Nat Commun. 2025; 16(1): 10583.

Fragile X syndrome (FX) is a leading inherited cause of autism spectrum disorder, characterized by sensory hypersensitivity and impaired visual learning. Visual experience induces synchronized theta oscillations in the primary visual cortex (V1) and lateromedial area (LM), supporting inter-areal sensory binding. Using the Fmr1 knockout (KO) mouse model of FX, we quantify experience-dependent c-Fos expression in V1 and LM via iDISCO whole-brain clearing. Simultaneous in vivo recordings and channelrhodopsin-2-assisted circuit mapping (CRACM) reveal synchronized V1-LM theta oscillations and strengthened feedforward V1 → LM connectivity in wild-type (WT) mice, but attenuated LM oscillations and impaired connectivity in FX mice. Using 4Pi single-molecule localization microscopy, we identify experience-driven dendritic spine remodeling in layer 5 pyramidal cells of V1 and LM in WT mice, which is absent in FX mice. FX mice also show elevated baseline spine density and length. Our findings demonstrate that visual experience drives inter-areal synchronization and synaptic plasticity, which are disrupted in FX.

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6. Christensen ZP, Freedman EG, Foxe JJ. Processing of Emotional Faces Has Unique Functional and Cytoarchitectural Associations in those with an Autism Spectrum Diagnosis. bioRxiv. 2025.

Those with an autism spectrum diagnosis (ASD) have been found to process emotional faces differently than other populations. Processing of emotional faces requires engagement of temporal, frontal, occipital, and limbic brain regions. Functional activity has been shown to differ in those with an ASD, particularly in the amygdala, inferior frontal cortex (IFC), and temporal brain regions. However, the consistency and direction of these associations have been inconsistent across studies. Recent findings have demonstrated that measures of neuron density differ in those with an ASD. Some of these regional differences in cytoarchitecture coincide with regions important to emotional facial processing. Therefore, the interaction between cytoarchitecture and functional activity may be important in elucidating unique neurophysiology in ASD. The present study uses diffusion weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data from the Adolescent Brain Cognitive Development (sm) (ABCD®) study to investigate the relationship between cytoarchitecture and functional activity during emotional face processing in those with an ASD. 75 individuals with a reported ASD and 6,396 individuals with no reported diagnosis of an ASD (nASD) were identified. The emotional n-back (EN-Back) task was administered during fMRI acquisition, activating regions of the brain associated with processing emotional faces. Neuron cell body density was positively correlated with functional activation in the left amygdala in the ASD group but not the nASD group. These findings suggest that a unique relationship may exist between neuron cell body density in the left amygdala and functional activity while processing emotional faces in those with an ASD.

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7. Çobanoğlu Osmanlı C, Baykal S, Önal BS, Şahin B, Bozkurt A. Comprehensive analysis of Guanfacine treatment in autism spectrum disorder with comorbid attention deficit hyperactivity disorder. Sci Rep. 2025.

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8. Dickson KS, Kennedy SM, Safer J, Brookman-Frazee L, Roesch S, Anthony LG. Study protocol for a hybrid type 2 effectiveness-implementation trial of two interventions for autistic and non-autistic youth in children’s mental health settings: one tailored for neurodivergence and one universal. Implement Sci Commun. 2025; 6(1): 131.

BACKGROUND: Mental health services play a key role in caring for autistic youth given the common and often unmet mental health needs in this population. There is a pressing need to enhance the uptake and use of evidence-based interventions (EBIs) that improve mental health services for autism and optimize outcomes. EBIs targeting transdiagnostic or key factors relevant across autism and mental health conditions exist and have the potential to enhance mental health services for autism. Yet, these interventions have not been widely tested. Similarly, autism EBI training is an implementation strategy with the potential to enhance mental health service quality broadly given specific components and strategies incorporated into the EBI to enhance its impact and fit. This protocol paper describes a multisite study that examines the clinical and implementation effectiveness of a transdiagnostic EBI developed for autistic children compared to a non-autism transdiagnostic EBI in children’s mental health settings (Aim 1), confirms engaged clinical and implementation mechanisms (Aim 2), and examines the generalized and expanded effects of EBI training beyond autism (Aim 3). METHODS: This study will employ a hybrid type 2 effectiveness-implementation design to test Unstuck and On Target, an executive functioning EBI adapted for mental health services (autism EBI) and Unified Protocol for Children (non-autism EBI). Twenty-eight mental health programs will be randomized to an EBI condition and 224 therapists across these programs will be recruited and receive EBI training. Additionally, 224 autistic children and 224 non-autistic children, yoked to participating therapists, will be recruited as EBI recipients. This study will measure clinical (mental health symptom change) and implementation outcomes (EBI fidelity, training engagement, psychotherapy quality, reach) and clinical (executive functioning skills, emotion regulation skills) and implementation (autism self-efficacy and knowledge, perception of fit) mechanisms. DISCUSSION: This study will confirm the effectiveness of a promising executive functioning EBI in mental health settings as well as generate clinical knowledge about the potential of transdiagnostic interventions improve mental health outcomes for autistic children. Findings also have immense potential to demonstrate the ability of autism EBIs to enhance mental health services for autistic and non-autistic children more broadly. TRIAL REGISTRATION: This study is registered with Clinicaltrials.gov (NCT06651086). Registered on October 18, 2024.

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9. Donald S, Sutherland HEA, Fletcher-Watson S. Doing research in services for autistic people with complex support needs: Challenges and considerations based on UK experiences. Autism. 2025: 13623613251390277.

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10. Guin D, Haditsch U, Bellucci JJ, Topka S, Dyer KE, Del Toro GAR, Blanco MR, Downs NF, Perfito N, Mahadevan A, Moxham CM. High-throughput transcriptomic screening reveals entrectinib as a repositioning opportunity in 19q12 autism spectrum disorder. Sci Rep. 2025; 15(1): 42001.

Discovering new and viable therapies for genetic diseases is a time-consuming and cost-intensive process, especially for rare disorders. In this study, we highlight how a high-throughput drug discovery platform was utilized to uncover drugs at scale that normalized the signature for a rare neurological neurodevelopmental disease, 19q12 autism spectrum disorder (ASD) associated with deficiencies in ZNF536 and TSHZ3. We first identified the transcriptomic fingerprint of the disease in an in vitro disease model in the form of dysregulated pathways. Subsequently, we measured the biological impact of small molecule drugs in a relevant wild-type cell line and uncovered an approved drug Entrectinib that induced the opposite effect to that in the disease fingerprint, demonstrating the capability to normalize the disease fingerprint. Entrectinib was further prescribed off-label to the identified patient with 19q12 and drug effect was characterized both from blood collection and neuropsychological assessments. Biomarkers from blood recapitulated Entrectinib’s pharmacodynamic effect and normalized the disease signature. We show how generation of transferrable transcriptomics-derived disease signatures allows for measuring drug effects on a signature in related wild-type cell lines, making the screen universally applicable and reducing the need for expensive screens in disease models.

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11. Kinfu KA, Pacheco C, Sperry AD, Crocetti D, Tuncgenc B, Mostofsky SH, Vidal R. Computerized Assessment of Motor Imitation for Distinguishing Autism in Video (CAMI-2DNet). IEEE Trans Biomed Eng. 2025; Pp.

Motor imitation impairments are commonly reported in individuals with autism spectrum conditions (ASCs), suggesting that motor imitation could be used as a phenotype for addressing autism heterogeneity. Traditional methods for assessing motor imitation are subjective and labor-intensive, and require extensive human training. Modern Computerized Assessment of Motor Imitation (CAMI) methods, such as CAMI-3D for motion capture data and CAMI-2D for video data, are less subjective. However, they rely on labor-intensive data normalization and cleaning techniques, and human annotations for algorithm training. To address these challenges, we propose CAMI-2DNet, a scalable and interpretable deep learning-based approach to motor imitation assessment in video data, which eliminates the need for ad hoc normalization, cleaning and annotation. CAMI-2DNet uses an encoder-decoder architecture to map a video to a motion representation that is disentangled from nuisance factors such as body shape and camera views. To learn a disentangled representation, we employ synthetic data generated by motion retargeting of virtual characters through the reshuffling of motion, body shape, and camera views, as well as real participant data. To automatically assess how well an individual imitates an actor, we compute a similarity score between their motion encodings, and use it to discriminate individuals with ASCs from neurotypical (NT) individuals. Our comparative analysis demonstrates that CAMI-2DNet has a strong correlation with human scores while outperforming CAMI-2D in discriminating ASC vs NT children. Moreover, CAMI-2DNet performs comparably to CAMI-3D while offering greater practicality by operating directly on video data and without the need for ad hoc normalization and human annotations.

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12. Kirby AV, Feldman K, Duncan-Ishcomer B, Kripke-Ludwig R, Joyce A, Lee W, Rodriguez K, Siddeek Z, Darlington A, Atisme A, Clark W, Murthi K, Wexler L, Nicolaidis C. Participatory Development of a Suicide Prevention Program for Autism Community Organizations. OTJR (Thorofare N J). 2025: 15394492251391675.

Participatory research is critical for developing appropriate and effective programs for specific communities. Suicide is a health inequity for autistic people and prevention is a high priority for autistic community members. Using community-based participatory research with autistic partners, we aimed to develop a research-informed, conceptually grounded, and community-supported suicide prevention program for the autism community. The participatory, multistep program development process included regular meetings to integrate existing research with an established intervention framework and was informed by 38 qualitative research interviews with autistic adults, family members, and mental health providers. The development process resulted in a four-part, virtual, education and community empowerment program-Forming Love around Autistic People to Prevent Suicide (FLAPS)-aimed at supporting organizations to engage in multilevel suicide prevention efforts. Participatory research that meaningfully engages autistic community partners can support the development of promising programs to promote suicide prevention for autistic people. Participatory Development of a Suicide Prevention Program for Autism Community OrganizationsThis paper describes work to make a new program to promote suicide prevention for the autistic community. Our team includes autistic people and academic researchers working together as partners. We worked together over several years to make a program based on research and community experience. We learned from an existing program for suicide prevention for Alaska Native youth. We also learned from interviews we did with 38 people including autistic adults, family members, and mental health providers. Through our process, we developed a four-part online program to educate and empower autism community organizations for suicide prevention. The program is called Forming Love around Autistic people to Prevent Suicide (FLAPS). The program has not been tested yet. eng.

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13. Kosloski EE, Rollins PR. Joint Engagement and Socially Motivated Language in Young Autistic Children. J Autism Dev Disord. 2025.

PURPOSE: This study investigated the social motivation underlying young autistic children’s language and time spent in engagement states [adapted from Bottema-Beutel et al., (2014) and ranging from less social to more social] during interactions with parents. We examined (1) autistic children’s time and words per minute (WPM) in each engagement state; (2) the relationship between time in engagement states and the social motivation (SM) of utterances; and (3) the effect of the Pathways intervention on time in engagement states. METHODS: This secondary analysis used video recordings of 10-min naturalistic interactions between 47 young autistic children (mean age = 36.23 months, SD = 7.89) and their parents. Families were randomized to either Pathways or services-as-usual (SAU). Videos were coded for engagement states, and child utterances were transcribed and coded for degree of SM using a novel coding scheme that captured attention (visual and auditory) and communicative intent. Data were analyzed using descriptive statistics, correlations, and hierarchical regression analyses. RESULTS: On average, children spent more time and produced more WPM during less social engagement states. Regression analyses revealed significant small-to-medium effects of (a) frequency of utterances with the lowest SM score on time in Object Engagement (less social; SAU > Pathways); and (b) frequency of utterances with higher SM scores on time in Coordinated Joint Engagement (more social; Pathways > SAU). CONCLUSION: Findings emphasize the difference between autistic children’s WPM and use of SM utterances, highlighting the need to differentiate expressive language from social language as distinct outcomes for this population.

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14. LaBianca S, Lousdal ML, Krebs MD, Hansen OS, Hellberg KG, Lundberg M, Sørensen J, Gaadin JR, Ohlsson H, Borglum A, Agerbo E, Werge T, Albinana C, Vilhjalmsson BJ, Kendler KS, Plana-Ripoll O, Schork AJ. As rates of ASD and ADHD rise, genetic contributions fall: Evidence for widening diagnostic criteria. medRxiv. 2025.

IMPORTANCE: The incidence of ADHD and autism spectrum disorder (ASD) has increased markedly over recent decades, raising concerns about the emergence of new risk factors. Current literature typically attributes increased rates to changes in diagnostic practice, stigmatization, and awareness, but critically few studies have explored changes in underlying risk factors. OBJECTIVE: To assess changes in the genetic risk profile of individuals diagnosed with ASD or ADHD according to year of incident diagnosis. DESIGN: We used the iPSYCH2015 study, a population-based case-cohort with complete ascertainment of incident diagnoses for ASD and ADHD made from 1994 to 2016. SETTING: Denmark. PARTICIPANTS: ASD (N=17,071) and ADHD (N=20,111). EXPOSURE: Year of incident diagnosis. Regression models tested changes in the mean genetic risk profile of individuals diagnosed in each consecutive year (1994-2016), adjusting for age, sex, and ancestry. MAIN OUTCOMES: We used polygenic scores for psychiatric (ADHD, ASD, depression, bipolar, schizophrenia) and cognitive-behavioral (addiction, educational attainment, IQ, neuroticism, risk-taking) outcomes to capture the genetic risk profiles of diagnosed individuals. RESULTS: A more recent ADHD diagnosis was associated (p<0.001) with less genetic risk for ADHD (β=-0.06 SD per 10 years) and other disorders (ASD, bipolar, schizophrenia). Similarly, a more recent ASD diagnosis was associated with less genetic risk for ASD (β=-0.07) and other disorders/traits (bipolar, schizophrenia, educational attainment). CONCLUSIONS AND RELEVANCE: Our novel approach suggests that over recent decades diagnostic practice around ADHD and ASD has evolved to capture a different profile of genetic risk. These findings support broadening diagnostic criteria as the explanation for the rise in incidence, with implications for understanding prevalence trends in relation to changes in risk factors and clinical practice. KEY POINTS: Question: Has the genetic risk profile of individuals diagnosed with autism spectrum disorder (ASD) and ADHD changed as diagnostic rates have risen?Findings: In the iPSYCH case-cohort study, we observed the genetic contributions to ASD and ADHD diagnoses have weakened over the past two decades.Meaning: Our results suggest that recent increase in ASD and ADHD diagnoses coincide with a broadening of diagnostic criteria.

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15. Li D, Chen H, Wang J, Zhang J, Zhao F, Xu L. ViT-CMN: a vision transformer framework based on fusion of low- and high-order dynamic central moment networks for autism spectrum disorder diagnosis. Cereb Cortex. 2025; 35(11).

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Current neuroimaging-based diagnostic methods often rely on functional connectivity features extracted from a single perspective, either low-order interactions or high-order co-fluctuations, limiting their capacity to capture the hierarchical and dynamic properties of brain networks. We propose ViT-CMN, a novel ASD diagnosis framework that integrates multilevel dynamic connectivity information from both low-order and high-order perspectives. First, dynamic functional connectivity networks are constructed using a sliding window approach to capture temporal variations. To enrich data diversity, a temporal reorganization-based augmentation strategy is introduced, which generates additional dynamic sequences by shifting their starting time points. For each sequence, seventh-order central moment features are extracted to enhance statistical stability over time. These multiview features are then structurally reorganized via a jigsaw-style fusion strategy into a unified 2D representation. This fused input is modeled using a Vision Transformer (ViT) to extract discriminative representations across spatial and hierarchical dimensions through self-attention mechanisms. Experiments on the autism brain imaging data exchange (ABIDE) dataset demonstrate that ViT-CMN outperforms existing baseline methods, achieving a top classification accuracy of 79.8%. The model also successfully identifies ASD-related brain regions that align with known neuropathological findings. ViT-CMN effectively addresses the limitation of single-view modeling in previous studies by structurally fusing heterogeneous dynamic features into a ViT-compatible form. The proposed approach provides a powerful and interpretable solution for ASD diagnosis, with strong potential for broader applications in neuroimaging-based disorder classification.

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16. Likhitweerawong N, Montanaro FAM, Santos ER, Wang JY, Dejputtawat W, Narasimhan U, Klusek J, Maltman N, Schneider A, Tassone F, Hagerman RJ. Swallowing and choking difficulties as potential markers of FXTAS progression in FMR1 premutation carriers. Sci Rep. 2025; 15(1): 42164.

Fragile X-associated tremor/ataxia syndrome (FXTAS) affects motor and coordination pathways and is linked to swallowing and choking difficulties, which can lead to aspiration pneumonia, a leading cause of death in late-stage FXTAS. Despite their severity, these issues are under-investigated. This study examined their association with FXTAS stages and potential as markers of disease progression in FMR1 premutation (PM) carriers. A secondary analysis of Genotype-Phenotype cohort data (2017-2025, MIND Institute, UC Davis) examined swallowing/choking problems, FXTAS stage, neuroimaging, and psychological distress (Symptom Checklist-90-Revised; SCL-90-R). Associations between independent and dependent variables were tested using Generalized Estimating Equation (GEE) regression due to their correlated data. The study included 169 PM carriers (mean age 65 ± 10.9 years; 54% male), with approximately 35% reporting swallowing/choking difficulties. After adjusting for age and sex, individuals in the severe stage of FXTAS (stage 4-5) had a significantly higher risk of swallowing/choking problems compared to those without FXTAS (adjusted odds ratio [aOR] = 4.17; 95%CI = 1.28-13.58). PM carriers with swallowing/choking problems showed a significantly increased association with magnetic resonance imaging (MRI) findings of moderate to severe abnormalities in several brain regions, including cerebral atrophy (aOR = 2.69, p = 0.027), cerebellar atrophy (aOR = 3.34, p = 0.013), cerebellar white matter hyperintensity (aOR = 3.33, p = 0.012), and pons white matter hyperintensity (aOR = 3.93, p = 0.035). Swallowing/choking problems are common in FXTAS, particularly in later stages, and may represent an important clinical marker of disease progression. These patients should be referred to speech-language pathologists for evaluation and treatment. Such interventions could reduce morbidity-mortality associated with these problems.

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17. Manning S, Van Esch N, Scheerer NE. Decreased sound tolerance in a Canadian University Context: Associations with autistic traits, social competence, and gender in an undergraduate sample. PLoS One. 2025; 20(11): e0334689.

Disorders of decreased sound tolerance such as misophonia and hyperacusis cause significant distress through strong negative emotional and physiological reactions to everyday sounds. These conditions have been associated with poor mental and physical health as they impact day to day life. Prior to the recent development of consensus definitions of misophonia and hyperacusis, attempts to determine the prevalence of these conditions have been hindered by the ambiguity and inconsistency of their descriptions. Despite this, certain populations have been suggested to more frequently experience misophonia and hyperacusis, namely younger people and autistic people. Furthermore, there has been conflicting evidence regarding whether these conditions are more prevalent among women. Post-secondary campuses are often sensory-rich. As such, students with misophonia and hyperacusis are likely to experience distress. For this reason, we sought to investigate the prevalence of misophonia and hyperacusis in a Canadian university sample, and explore the relations between these conditions and gender, autistic traits, and overall social competence. As exposure to many everyday sounds can be highly aversive for individuals with misophonia and/or hyperacusis, these individuals often attempt to avoid environments in which distressing sounds are encountered. It is therefore possible that poorer social competence may be a secondary effect of these conditions. To investigate these relations, 2080 students completed an online survey using multiple established self-report measures of decreased sound tolerance. Clinical misophonia was detected in 12-18% of participants, and hyperacusis in 6-17%. Both conditions were significantly more prevalent among women than men. Both conditions were found to be weakly to moderately positively correlated with autistic traits, and weakly to moderately negatively correlated with social competence. These results highlight decreased sound tolerance as a significant issue at Canadian post-secondary institutions, calling for steps to be taken to mitigate its effects.

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18. Mori H, Takahashi M, Monden R, Adachi M, Hirota T, Shinkawa H, Osada M, Adachi M, Nakamura K. Autism and ADHD traits, effortful control and mental health during the transition from elementary to junior high schools. Sci Rep. 2025; 15(1): 42262.

The transition from elementary to junior high school presents developmental challenges, particularly for students with neurodevelopmental traits. This study examined how autism, attention-deficit/hyperactivity disorder (ADHD) traits and effortful control (EC) were related to changes in mental health during this transition in a large Japanese community sample (N = 2,564). This longitudinal study used data from a community-based cohort of Japanese students and their parents/guardians (N = 2,692). Autism traits were measured using the Autism Spectrum Screening Questionnaire (ASSQ). ADHD traits were assessed with the Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS). Effortful control (EC) was evaluated using the « Effortful Control » subscale of the Early Adolescent Temperament Questionnaire-Revised (EATQ-R). Mental health problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) before and after the transition. Generalized estimating equations (GEE) and latent profile analysis (LPA) were conducted to examine associations among autism and ADHD traits, EC, and mental health across the transition. GEE revealed that higher autism and ADHD traits and lower EC predicted more severe mental health problems. The LPA identified three distinct subgroups characterized by high, moderate, and low SDQ scores across the transition. The high-SDQ group showed elevated autism and ADHD traits and low EC, whereas the low-SDQ group showed low auism and ADHD traits and high EC. The moderate group exhibited intermediate levels for all measures. These findings suggest that pre-existing mental health problems tend to persist during the transition period. Importantly, students with higher autism and ADHD traits and lower EC exhibited diverse adaptation patterns-some improved while others worsened-highlighting that high autism traits are not necessarily associated with post-transition mental health deterioration. This underscores the need for support tailored to neurodevelopmental and self-regulatory profiles.

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19. Nautiyal H, Jaiswar A, Roy KK, Dwivedi S. Deciphering the molecular connections between polycystic ovarian syndrome and autism spectrum disorder using bioinformatic analysis. Horm Behav. 2025; 177: 105859.

Epidemiological studies show a positive association between polycystic ovarian syndrome (PCOS) and autism spectrum disorder (ASD), potentially due to elevated prenatal testosterone levels, supporting the prenatal sex steroid theory. However, the molecular mechanisms behind this association remain unclear. This study investigates the association between PCOS and ASD by identifying shared hub genes and exploring molecular mechanisms using publicly available gene expression datasets (GSE1615, GSE5850, GSE10946, GSE80432, and GSE28521). We analysed these datasets for identifying differentially expressed genes (DEGs) and pathways using bioinformatic tools such as GEO2R, STRING, Enrichr, and Cytoscape. Sixty-three overlapping DEGs were identified, along with shared pathways related to hormone receptor signalling, synaptic function, and metabolic regulation. Network analysis highlighted hub genes (TP53, MAPK1, MAPK14, AR, ESR1, CCND1, EP300), regulatory microRNAs and transcription factors with potential roles in both disorders. Drug signature enrichment via DSigDB identified candidate small molecules through hypothesis generating prediction, including celecoxib, N-acetylcysteine and other drug molecules. Elevated maternal androgens are proposed as a shared environmental factor that may interact with molecularly regulated pathways, contributing to the observed molecular convergence. While the study integrates multiple well-curated datasets, sample sizes were modest, and analysis were performed exclusively in silico without experimental validation. These findings provide insight into the potential mechanistic overlap between PCOS and ASD, highlighting the molecular targets for future functional and translational studies, while underscoring the need for careful interpretation in maternal-fetal health contexts.

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20. Pulatov O, Nguyen W, Vega DA, Barros R. A novel de novo missense variant in ASH1L associated with mild autism spectrum disorder and an uneven cognitive profile: a case report. J Med Case Rep. 2025; 19(1): 616.

BACKGROUND: ASH1L-related intellectual developmental disorder represents an emerging neurodevelopmental syndrome with significant phenotypic heterogeneity (Cordova et al. in Genes (Basel). 15(4):423, 2024). Comprehensive genomic analysis demonstrates superior diagnostic yield compared with targeted approaches in complex neurodevelopmental presentations (Srivastava et al. in Genet Med. 21(11):2413-2421, 2019). CASE PRESENTATION: This report describes a 6-year-old Central Asian (Uzbek) male patient with a history of global developmental delay who was diagnosed with mild autism spectrum disorder, attention-deficit/hyperactivity disorder, and a developmental expressive language disorder. Neuropsychological assessment revealed an uneven cognitive profile with average verbal abilities but below-average nonverbal reasoning. After uninformative targeted genetic panels, trio whole-genome sequencing identified a novel de novo heterozygous missense variant in ASH1L c.4043A > G (p.Lys1348Arg). This variant, absent in population databases, was classified as a variant of uncertain significance. However, in silico analysis predicted this variant to be probably damaging, and therefore, it emerged as the strongest candidate to explain the patient’s phenotype. CONCLUSION: This case expands the known phenotypic spectrum of ASH1L-related disorders, demonstrating that a de novo missense variant can be associated with a milder neurodevelopmental phenotype, including borderline-to-average intellectual ability. These findings challenge suggestions that missense variants uniformly lead to more severe outcomes and underscores the importance of comprehensive genomic and deep clinical characterization to refine our understanding of gene-disease relationships.

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21. Qiao SN, Jiang YH. Heightened empathic responses led by imbalanced cortico-amygdala circuit in Shank3 autism mouse model. bioRxiv. 2025.

Affective empathy is defined as individual percept and respond to another emotion appropriately, an essential building block for human society. Historically, aberrant empathy was considered as major characteristics of autistic individuals but recently it has been challenged. It required mechanistic understanding of the empathy process, especially how autistic individual percept other emotion. By evaluating the social fear transfer response, we reported a critical role of Shank3 gene, one of the most replicated causative autism genes, in cortico-amygdala circuit in balancing and integrating affective empathy process using preclinical mouse models. We found that Shank3 complete deletion mouse model exhibited unexpected exaggerated affective responses, which was encoded by defective neural dynamics of Shank3 -deficient cingulate projecting amygdala circuit. This work for the first time showcased an interplay between gene and affective empathy responses in mouse and laid the groundwork for modeling empathy in autism and other neuropsychiatric disease.

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22. Rock K. Autistic people are still let down by public services-new government strategy must deliver change. Bmj. 2025; 391: r2481.

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23. Roper S, Charlton R, Happé F, Stewart GR. Self-harm and suicidality experiences of autistic and non-autistic adults in midlife and old age. Mol Autism. 2025; 16(1): 58.

BACKGROUND: Suicide has been reported as a leading cause of premature death in autistic populations. Additionally, risk of suicidality is often found to increase with age in the general population. Despite this, suicidality has seldom been explored in autistic populations in midlife and old age. This study investigates the self-reported prevalence of self-harm and suicidality in autistic people in midlife and old age compared to an age- and gender-ratio comparable non-autistic group. METHODS: In total, 388 participants (autistic n = 222, 44% men) aged 40-93 years (mean = 60.9 years) from the AgeWellAutism study completed questionnaires related to experiences of suicidal ideation, self-harming thoughts, deliberate self-harm, and suicidal self-harm. Group, gender and age differences were examined in chi-square and linear regression analyses. RESULTS: The autistic group reported significantly higher rates of suicidal ideation, self-harming thoughts, deliberate self-harm, and suicidal self-harm than the non-autistic comparison group. When considering gender differences in the autistic group (but not the non-autistic group due to limited sample size), autistic women reported significantly higher rates of suicidal ideation and suicidal self-harm compared to autistic men; no other gender differences were found. When considering age differences, autistic people in old age were more likely to have had thoughts of self-harm, to have deliberately self-harmed, and to have experienced suicidal self-harm than autistic people in midlife. LIMITATIONS: The AgeWellAutism study is a cross-sectional convenience sample that relies on self-report. Survivor bias may also influence findings, as the study design would exclude those who have died by suicide, potentially leading to an underestimation of suicidality. CONCLUSIONS: Autistic adults may be particularly susceptible to experiences of self-harm and suicidality in midlife and old age, particularly autistic women. Additionally, autistic people in old age were also more likely to experience suicidality (including recent experiences) than autistic people in midlife. These findings highlight the urgent need for targeted suicide prevention strategies and mental health interventions for autistic adults in midlife and old age, particularly autistic women and older people.

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24. Sonn JY, Kim W, Iwanaszko M, Aoi Y, Li Y, Qi G, Parkitny L, Brissette JL, Weiner L, Botas J, Al-Ramahi I, Shilatifard A, Zoghbi HY. MeCP2 interacts with the super elongation complex to regulate transcription. Sci Adv. 2025; 11(48): eadt5937.

Loss-of-function mutations in methyl-CpG binding protein 2 (MECP2) cause Rett syndrome. While we know that MeCP2 binds to methylated cytosines on DNA, the full breadth of the molecular mechanisms by which MeCP2 regulates gene expression remains incompletely understood. Here, using a genetic modifier screen, we identify the super elongation complex, a P-TEFb-containing elongation factor that releases promoter-proximally paused RNA polymerase II, as a genetic interactor of MECP2. MeCP2 physically interacts with SEC subunits and directly binds AFF4, the scaffold of the SEC, via the transcriptional repression domain. Furthermore, MeCP2 facilitates the binding of AFF4 on a subset of genes in the mouse brain regulating synaptic plasticity and concordantly promotes the binding of RNA polymerase II on these genes. Last, while haploinsufficiency of Aff4 does not exhibit any behavioral deficits in mice, it exacerbates the impaired contextual learning behavior of Mecp2 hypomorphic mice. We propose a previously unknown mechanism by which MePC2 regulates gene expression underlying synaptic plasticity.

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25. Tecar C, Chiperi LE, Iftimie BE, Popa LL, Sas V, Stefanescu E, Vacaras V, Muresanu DF. Sleep Disturbances and Behavioral Problems in Children and Adolescents with Autism Spectrum Disorder-A Systematic Review. Clin Pract. 2025; 15(11).

Background/Objectives: Sleep disturbances are among the most prevalent and persistent comorbidities in children and adolescents with autism spectrum disorder (ASD), affecting up to 83% of this population. These disturbances not only impact the quality of life but are increasingly recognized as significant contributors to behavioral dysregulation. Methods: This systematic review synthesizes evidence from 26 studies published between 2010 and 2024, examining the association between sleep problems and behavioral outcomes in individuals with ASD aged 2 to 18 years. Results: The findings reveal consistent associations between sleep-onset insomnia, night walking, bedtime resistance, and various behavioral difficulties, including aggression, hyperactivity, and emotional dysregulation. Internalizing symptoms and exacerbation of core ASD features were also linked to chronic sleep problems. Studies employing objective sleep measures, such as actigraphy and polysomnography, further supported these associations by identifying disruptions in sleep architecture correlated with behavioral severity. While most included studies were of moderate to high methodological quality, the limited number of randomized controlled trials and heterogeneity of sleep and behavior assessment tools highlight the need for standardization. Conclusions: Overall, the review emphasizes the importance of routine sleep evaluation in ASD clinical care and supports targeted sleep interventions as a potential strategy to reduce behavioral problems and improve developmental outcomes.

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26. Toprak TB, Özçelik HN, Işık HR. A brief religiously-adapted cognitive behavioral therapy intervention for Acute Stress Disorder (ASD) after Kahramanmaraş earthquake in Türkiye: a case series. BMC Psychiatry. 2025; 25(1): 1123.

BACKGROUND: After earthquakes, disaster survivors frequently experience acute psychological distress and require time- and resource-efficient, accessible, and culturally sensitive interventions. Integrating religious values into psychological interventions may enhance acceptability and effectiveness in such contexts. METHODS: This case series aimed to develop a brief religiously-adapted cognitive behavioral therapy (CBT) intervention program sensitive to religious values for individuals experiencing acute stress symptoms. Seven earthquake survivors with acute stress symptoms participated. The DSM-5 Acute Stress Symptoms Severity Scale was used for initial screening, and the Stress Symptoms Subscale of the Posttraumatic Diagnostic Scale (PDS) was used to assess symptom severity at pre-intervention, post-intervention, and at 1-week, 1-month, and 1-year follow-up. Participants received a 5-session, 2.5-week intervention designed in consultation with religious authorities and trauma experts. The study was conducted in March 2023. RESULTS: The intervention appeared to contribute to a notable reduction in posttraumatic stress symptoms. On average, participants exhibited a 46% decrease in scores on the PDS Stress Symptoms Subscale following the intervention. These improvements were sustained across all follow-up periods. CONCLUSIONS: The brief religiously-adapted cognitive behavioral therapy intervention for ASD appears to be a feasible and practical short-term approach for reducing acute stress symptoms and potentially preventing the development of PTSD in post-earthquake populations seeking religious-sensitive psychological care.

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27. Vanneau T, Foxe JJ, Beker S, Molholm S. Disrupted Top-Down Modulation as a Mechanism of Impaired Multisensory Processing in Children with an Autism Spectrum Diagnosis. bioRxiv. 2025.

Atypical sensory processing is a core feature of autism, particularly when integration across sensory modalities is required. The neural mechanisms underlying these multisensory differences remain unclear. We recorded high-density EEG while autistic children aged 8-13 (AU; n=40), unaffected siblings of autistic children (SIB; n=26), and non-autistic controls (NA; n=36) performed a simple reaction-time task to auditory (A), visual (V), and audiovisual (AV) stimuli. Analyses targeted event-related potentials (ERPs; P1/N1/P2), alpha-band event-related desynchronization (α-ERD), and long-range theta-band functional connectivity (weighted phase-lag index, wPLI). Across all unisensory measures (ERPs, α-ERD, and connectivity), groups did not differ, indicating broadly comparable unisensory processing. By contrast, multisensory integration (MSI; operationalized for ERPs and α-ERD as AV – (A+V)) differed across groups: NA children showed significant ERP MSI over parieto-central sites that was absent in AU and SIB; and α-ERD MSI was present in all groups but significantly reduced in AU, with SIB showing an intermediate profile. Connectivity analyses revealed that AV theta-band fronto-parieto-occipital coupling was reduced in autistic relative to non-autistic children, consistent with weaker large-scale coordination during multisensory processing. Together, these results point to a multisensory-specific deficit in autism spanning early sensory encoding, posterior α-ERD, and fronto-posterior coupling. The convergence of results supports a mechanistic account of disrupted multisensory influences on sensory processing due to reduced multisensory attentional orientation. Intermediate SIB profiles suggest inherited liability for these neural phenotypes. These results help explain well-documented behavioral MSI differences in autism by linking impaired early enhancement with attenuated top-down control of sensory cortex.

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28. Yuan Y, Li Y, Yang F, Jiang Y, Ding Y, Xiao Y, Zhu X, Shu X, Huang X, Wang Y, Zhang S, Sun J, Xu Z. Sh3rf3 Deficiency drives autism-like behaviors via presynaptic dysfunction in mice. Mol Psychiatry. 2025.

Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder with a strong genetic basis. Although SH3RF3 has been identified as an ASD candidate gene, its biological function and pathophysiological mechanisms remain elusive. Here, we reveal that SH3RF3 functions as an essential scaffold protein that facilitates presynaptic vesicle docking. Mechanistically, it orchestrates the formation of a molecular complex between the kinase BRSK1/SAD-B and the ASD-associated active zone protein RIM1. Genetic ablation of Sh3rf3 disrupts this protein-protein interaction, leading to reduced RIM1 phosphorylation. This perturbation triggers synaptic dysfunctions, marked by a substantial reduction in both total synaptic vesicle (SV) density and readily releasable pool size, coupled with delayed SV replenishment kinetics. These deficits ultimately impair excitatory synaptic transmission in the prefrontal cortex, disturb the excitatory-inhibitory (E/I) balance, and elicit autistic-like behaviors in mice. Notably, prefrontal cortex-specific restoration of Sh3rf3 reverses behavioral and functional deficits in knockout mice. Furthermore, our characterization of the SH3RF3 interactome reveals a shared molecular network encompassing ASD-risk genes, indicating that synapse-targeted therapies may have broad applicability.

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29. Zhu Y, Li D, Hu C, Tian Y, Lu P, Hagerman RJ, Xu X, Xu Q. Effects of Metformin on children with Fragile X Syndrome: a randomized, double-blind, placebo-controlled trial. Mol Autism. 2025; 16(1): 57.

BACKGROUND: Fragile X Syndrome (FXS) is the most prevalent inherited intellectual disability disorder linked to the X chromosome, and currently lacks an approved specific treatment. Preclinical and some clinical studies have suggested metformin may have therapeutic potential for FXS based on its mechanisms related to the disorder’s pathophysiology. METHODS: We conducted a 6-month, randomized, double-blind, placebo-controlled trial at the Children’s Hospital of Fudan University. Thirty-four participants aged 2-16 years with genetically confirmed FXS were randomized 1:1 to receive weight-adjusted metformin (250-1000 mg/day) or placebo. Primary outcomes were changes in Aberrant Behavior Checklist (ABC); secondary outcomes included Griffiths Development Scale-Chinese (GDS-C), Autism Diagnostic Observation Program Second Edition (ADOS-2), Children’s Sleep Habits Questionnaire (CSHQ), Repetitive Behavior Scale-Revised Chinese version (RBS-R), and Clinical Global Impression (CGI). RESULTS: Among 34 randomized participants, 30 completed the trial (15 per group). Metformin demonstrated significant improvements in hyperactivity (ABC-Hyperactivity: -7.86 ± 6.97 vs. -0.80 ± 8.09, p = 0.016) and sleep disturbances (CSHQ-Total: -0.73 ± 5.14 vs. + 5.13 ± 6.85, p = 0.013), particularly bedtime resistance (p = 0.004). Total ABC score reductions favored metformin (-16.60 ± 15.31 vs. -4.00 ± 23.67) but did not reach significance (p = 0.095). No significant between-group differences were observed in cognitive, social, or repetitive behavior measures (GDS-C, ADOS-2, RBS-R). Adverse event rates were comparable, with IGF-1 reduced (6.7%, p = 1), transient appetite loss (13.3%, p = 0.483) and lactic acidosis (26.7%, p = 0.330) resolving spontaneously in metformin group. LIMITATION: This study was constrained by its modest sample size (n = 30), and absence of objective neurophysiological measures. The 6-month duration precluded assessment of long-term therapeutic effects. CONCLUSIONS: In this controlled trial, metformin did not significantly improve the primary outcome of ABC total score. However, significant improvements were observed in the hyperactivity subscale and key secondary outcomes, including sleep parameters, while maintaining a favorable safety profile. Although the primary endpoint was not met, these secondary findings support further investigation of metformin for targeted behavioral domains in individuals with FXS. TRIAL REGISTRATION: This trial was prospectively registered on ClinicalTrials.gov (Registration No. NCT05120505, first posted November 03, 2021). The full protocol can be accessed at https://register. CLINICALTRIALS: gov/ .

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30. Zhu Y, Su X. Do Children with Autism Spectrum Disorders (ASD) Have Deep Learning Ability? An Exploratory Research in Inclusive Play. J Intell. 2025; 13(11).

Deep learning ability is critical for children’s development, yet little research has been conducted on preschool children with autism spectrum disorders (ASD). This study investigated the deep learning ability of children with ASD in inclusive play, which involved 8 children with ASD and 13 children with typical development (TD) (5-7 years of age) from four public kindergartens in China. An assessment scale for children’s deep learning ability was developed, and children were observed during inclusive play (IP) and solitary play (SP) in natural settings. A total of 40 play cases (10 were IP and 30 were SP) were collected. Key findings indicated that (1) children with ASD had a moderate level of deep learning ability during play, the emotional experience scored the highest while the interpersonal interaction scored the lowest. (2) The score of deep learning ability in children with ASD in SP was higher than that in IP. (3) Monthly per capita household income, father’s occupation, siblings, and primary playmates significantly influenced the deep learning ability of children with ASD. This study provided new insights into deep learning during play for children with ASD and offered an empirical basis for future inclusive education.

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31. Zubizarreta SC, Isaksson J, Faresjö Å, Faresjö T, Carracedo A, Prieto MF, Bölte S, Lundin Remnélius K. The impact of camouflaging autistic traits on psychological and physiological stress: a co-twin control study. Mol Autism. 2025; 16(1): 59.

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