1. Capps MES, Moyer AJ, Conklin CL, Martina V, Torija-Olson EG, Klein MC, Gannaway WC, Calhoun CCS, Vivian MD, Thyme SB. Disrupted diencephalon development and neuropeptidergic pathways in zebrafish with autism-risk mutations. Proc Natl Acad Sci U S A;2025 (Jun 10);122(23):e2402557122.

Hundreds of human mutations are linked to autism and related disorders, yet the functions of many of these mutated genes during vertebrate neurodevelopment are unclear. We generated 27 zebrafish mutants with presumptive protein-truncating mutations or specific missense variants corresponding to autism-risk alleles in 17 human genes. We observed baseline and stimulus-driven behavioral changes at larval stages, as well as social behavior differences in lines tested as juveniles. Imaging whole-brain activity revealed a near identical activity map for mutations in the unrelated genes kmt5b and hdlbpa, defined by increased activity mainly in the thalamus and mesencephalon. Mutating 7 of the 17 risk genes resulted in substantial brain size differences, localized to the diencephalon in three cases and more widespread in others. Using RNA sequencing, we further defined molecular drivers of the observed phenotypes for three mutants, identifying targetable disruptions in neuropeptide signaling, neuronal maturation, and cell proliferation. This multimodal screen nominated brain regions, cell types, and molecular pathways that may contribute to autism susceptibility.

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2. Carter E, Joseph F. A qualitative study into the experiences of families affected by developmental disorders seeing the UK NHS Genetics Service; if I had known then what I know now. J Genet Couns;2025 (Jun);34(3):e70063.

Parents of a child with a developmental disorder (DD) experience significant challenges, such as prognostic uncertainty, lack of care coordination, stigmatization, and changes to social and financial positions. Limited research exists into whether parents’ support needs are being met by the United Kingdom National Health Service (UK NHS) Genetics Service. Therefore, this study aimed to establish whether these parents feel adequately supported by the UK NHS Genetics Service and, if not, what further support could be provided. This study recruited participants through the Unique and SWAN UK support groups. Fourteen parents of children with a DD took part in semi-structured interviews. Four overarching themes were identified: Expectations, the impact of the delivery of the diagnosis, uncertainty about who has medical responsibility, and isolation. While some positive experiences were described, parents also revealed expectations of support from the Genetics Service that were not met. These expectations included support with care coordination, a medical professional to take a holistic approach, and being signposted effectively to support networks. The analysis suggests that patient expectations of the Genetics Service need to be managed prior to the first appointment and that parents would benefit from access to a dedicated care coordinator. Furthermore, signposting to support groups is inconsistent. Future research should focus on identifying families most in need of support so that these families can be prioritized for the limited resources and investigate how best to prepare patients for receiving a diagnosis.

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3. Chen X, Zhang J, Wu J, Robinson MJ, Kothandaraman H, Yoo YE, Dopeso-Reyes IMG, Buffenoir TD, Halurkar MS, Zhang Z, Wang M, Creager EN, Zhao Y, Olivero-Acosta MI, Wettschurack KW, Que Z, Yuan C, Schaser AJ, Lanman NA, Rochet JC, Skarnes WC, Kremer EJ, Yang Y. Autism-associated SCN2A deficiency disrupts cortico-striatal circuitry in human brain assembloids. bioRxiv;2025 (Jun 3)

Profound autism spectrum disorder (ASD) is frequently attributable to single-gene mutations, with SCN2A (voltage-gated sodium channel Na (V) 1.2) protein-truncating variants (PTVs) being one of the most penetrant. Although cortico-striatal circuitry is implicated as a key node in ASD, the impact of SCN2A deficiency on human neural circuits is unknown. Using the human cortico-striatal assembloid model, we show that the autism-causing PTV SCN2A-C959X impairs long-range cortical axonal projections, reduces striatal spine density, and attenuates excitatory cortical-striatal synaptic transmission. Surprisingly, these assembloids carrying the heterozygous SCN2A nonsense mutation exhibited pronounced network hyperexcitability, a human cell-specific phenotype not observed in Scn2a (+/-) mice, highlighting a human-specific circuit vulnerability. Collectively, our study unveils human circuit-specific dysfunctions of SCN2A deficiency and SCN2A -mediated ASD. HIGHLIGHTS: Axonal projections facilitate synapse formation and functional connectivity in human brain assembloids. Na (V) 1.2 is expressed along neuronal axons, extending to soma and dendrites in human brain assembloids. SCN2A-C959X disrupts axonal projection patterns, impairs excitatory synaptic transmission, reduces spine density, and results in elevated neuronal excitability. GRAPHICAL ABSTRACT: In brief: SCN2A haploinsufficiency impairs cortico-striatal circuitry.: SCN2A haploinsufficiency disrupts axon initial segment (AIS) integrity, leading to hyperexcitability (red arrow), reduced axon projections, and impaired synaptic transmission (decreased sEPSCs and altered network firing). These deficits result in dysfunction within the cortico-striatal circuitry.

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4. Daffner-Deming M, Savant D, Blakey-Armstrong A, Thom RP, Howe YJ, Fogler J, Diekroger EA. Co-occurring Anxiety in a Child With Autism and ADHD. J Dev Behav Pediatr;2025 (Jun 3)

KM is an 11-year-old autistic boy followed by a developmental-behavioral pediatrician (DBP) practicing within a multidisciplinary autism center. He had been prescribed various attention-deficit hyperactivity disorder (ADHD) medications over the years, most recently dextroamphetamine-amphetamine extended-release capsule 10 mg daily.KM initially presented to the DBP for diagnostic confirmation of autism and ADHD at the age of 7 years. His school had conducted a detailed evaluation the year prior, indicating skills in the borderline range for cognitive, adaptive, and language functioning. Based on his developmental history, physical examination, review of school-based testing, and parent- and school-completed standardized questionnaires, he met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for autism spectrum disorder and ADHD with combined presentation.When KM was between the ages of 8 and 10 years, he trialed several medications, including methylphenidate (which led to emotional lability), dextroamphetamine sulfate oral solution (which caused irritability), and clonidine (which led to destructive behavior). Notably, KM’s parents were divorced and had differing opinions and experiences surrounding the efficacy and tolerability of his medications, which made medication trials more complex. He eventually was stabilized on extended-release dextroamphetamine-amphetamine at the age of 9 years, which both parents agreed was helpful for improving attention, despite the medication triggering a new self-injurious behavior of punching himself.At the age of 10 years, after 1 year of stability on dextroamphetamine-amphetamine extended-release capsule 10 mg daily, his parents chose not to refill the medication, to see whether it was still helpful for him. They observed that he seemed much « happier » with improved mood and decreased anxiety when dextroamphetamine-amphetamine was withheld; however, they did note worsened hyperactivity. A few weeks later, he began demonstrating increased symptoms of anxiety such as somatization and externalizing behaviors. This included frustration, aggression, and oppositionality, especially in anticipation of and/or when confronting anxious stimuli.His neuropsychologist and DBP collaborated to create a behavior monitoring plan to help his parents clarify and track his symptoms across households, with the goal of monitoring symptom severity and differentiating ADHD from anxiety-related symptoms. Because of this, his parents identified hyperactivity and impulsivity as KM’s most problematic symptoms; therefore, dextroamphetamine-amphetamine extended-release 10 mg daily was restarted. Although this was effective for his hyperactivity, ongoing monitoring suggested that his anxiety symptoms continued to be clinically significant. The DBP consulted a psychiatrist who advised a trial of escitalopram in conjunction with dextroamphetamine-amphetamine. Several weeks after starting escitalopram 5 mg per day, KM exhibited reduced anxious thoughts and decreased aggression, but ongoing symptoms of inattention.Considering KM’s complex presentation, how do we approach neuropsychological assessment, behavioral and therapeutic support, and psychopharmacology?

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5. Daniel E, Gulati A, Saxena S, Urgun DA, Bista B. GM-VGG-Net: A Gray Matter-Based Deep Learning Network for Autism Classification. Diagnostics (Basel);2025 (Jun 3);15(11)

Background: Around 1 in 59 individuals is diagnosed with Autism Spectrum Disorder (ASD), according to CDS statistics. Conventionally, ASD has been diagnosed using functional brain regions, regions of interest, or multi-tissue-based training in artificial intelligence models. The objective of the exhibit study is to develop an efficient deep learning network for identifying ASD using structural magnetic resonance imaging (MRI)-based brain scans. Methods: In this work, we developed a VGG-based deep learning network capable of diagnosing autism using whole brain gray matter (GM) tissues. We trained our deep network with 132 MRI T1 images from normal controls and 140 MRI T1 images from ASD patients sourced from the Autism Brain Imaging Data Exchange (ABIDE) dataset. Results: The number of participants in both ASD and normal control (CN) subject groups was not statistically different (p = 0.23). The mean age of the CN subject group was 14.62 years (standard deviation: 4.34), and the ASD group had mean age of 14.89 years (standard deviation: 4.29). Our deep learning model accomplished a training accuracy of 97% and a validation accuracy of 96% over 50 epochs without overfitting. Conclusions: To the best of our knowledge, this is the first study to use GM tissue alone for diagnosing ASD using VGG-Net.

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6. Day RH, Cooper S, Sanoudaki E. Bilingualism in the preserved speech variant of Rett syndrome: A longitudinal case study. Clin Linguist Phon;2025 (Jun 3):1-20.

Rett syndrome (RTT) is a neurodevelopmental condition affecting physical and linguistic development. To the authors’ knowledge, there have been no studies published documenting bilingual linguistic abilities in an individual with RTT. Recent studies have found no evidence of a detrimental effect of bilingual exposure on language development in numerous other neurodevelopmental conditions. The aims of this study were to document bilingualism in RTT and to assess the development of language skills over time. A longitudinal, single-case study approach was taken for this research. The participant was a female adolescent with the preserved speech variant of Rett syndrome (PSV RTT), who had been exposed to both English and Welsh from birth. Data collection comprised administering parental questionnaires, documenting expressive vocabulary, and repeated administration of standardised English- and Welsh-medium tests at 18-month intervals. Repeated measures showed an improvement in linguistic and non-linguistic abilities between data points 1 and 2. There was a growth in English and Welsh expressive vocabulary in line with the participant’s level of exposure to each language. Further increases in English and Welsh vocabulary comprehension were seen at the third data point after changes in the amount and mode of language exposure received. This study is the first to document bilingualism in RTT, including the development of receptive and expressive abilities in both languages over time. This study found no evidence of a detrimental effect of bilingualism in this individual and highlights the need for further research into bilingualism in RTT.

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7. Dougnon G, Matsui H. Three decades of neuroscience research using animal models of ADHD and ASD: a bibliometric analysis. Front Psychiatry;2025;16:1528205.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are two increasingly prevalent neurodevelopmental disorders (NDDs), often accompanied by significant daily-life challenges. Animal models play a crucial role in studying these conditions, and recent advances have highlighted the potential of animal models such as mice, rat, zebrafish, Drosophila or Caenorhabditis elegans for investigating NDDs. However, despite growing interest, a complete understanding of these disorders has yet to be achieved. We believe that to properly address these NDDs, it is important to analyze the heterogeneity of ADHD and ASD research. METHODS: This study comprehensively analyzes ADHD and ASD-related scientific publications from January 1990 to December 2023 using data from the Web of Science (WoS), exploring trends in global research output, impact factors, citation metrics, the predominant use of animal models, the contribution of major countries and funding information. RESULTS: Out of the 10,844 papers from WoS, we curated 5,883 papers and identify mice and rat as the primarily used animal models, and a progressive use of zebrafish, Drosophila and C. elegans since the early 2000s. The countries conducting research on ADHD and ASD were principally the United States (3,059 articles), followed by China (487 articles), the United Kingdom (459 articles), Japan (440 articles), Germany (413 articles). We further show that impact factors and journal citations were relatively similar among the major publishing countries. Interestingly, key research funders were the National Institute of Health (NIH), the National Institute of Mental Health (NIMH), and the Japanese Ministry of Education Culture Sports Science and Technology (MEXT), making important contributions to their respective countries’ publications. Of note, Africa and Oceania have a lower volume of publication; however, our network analysis indicates a recent peak in research interest and ADHD/ASD awareness in some countries like Ghana or Portugal. CONCLUSION: The findings highlight significant advancements and collaborative efforts in ADHD and ASD research over the last three decades, underscoring the importance of international cooperation in addressing these complex neurodevelopmental disorders.

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8. Ebrahimiazar S, Kikkawa T, Minakuchi Y, Miyashita S, Manabe S, Hoshino M, Toyoda A, Osumi N. A Transcriptomic Dataset of Embryonic Murine Telencephalon of Fmr1-Deficient Mice. Sci Data;2025 (Jun 2);12(1):927.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. FXS patients exhibit autistic behaviors and abnormal brain structures, with notable sex differences. However, the mechanisms by which Fmr1 deficiency leads to these sex differences during brain development remain unclear. In this study, we performed bulk RNA sequencing on telencephalon samples of Fmr1-knockout mice of both sexes at embryonic day (E) 14.5, i.e., at the peak of neurogenesis. Clustering analysis revealed gene expression differences influenced by Fmr1 gene dosage and sex. We found that majority of the transcripts were shared between male and female sample groups, while a smaller number were unique to each sex. Our dataset underscores the importance of studying brain development during the embryonic period to detect sex-dependent genetic factors which contribute to neurodevelopmental disorders.

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9. Haebig E, West S, Jiménez E, Hills TT, Cox CR. Network Analysis of Autistic Language Learners Along the Small World Spectrum. Autism Res;2025 (Jun 2)

Recent network analyses of vocabulary growth revealed important relationships between the structure of the semantic environment and early vocabulary acquisition in non-autistic children. However, autistic children may be less likely to encode associated features of novel objects, suggesting divergent processes for acquiring semantic information about words. We examined the expressive vocabularies of 815 non-autistic and 163 autistic children (words produced: M(Autistic) = 183.06, M(Non-autistic) = 182.91). We estimated their trajectories of semantic development using network analyses. Network structure was based on child-oriented word associations. We analyzed networks according to indegree, average shortest path length, clustering coefficient, and small-world propensity (features holistically contributing to « small-world » network structure). Analyses revealed that autistic and non-autistic children are sensitive to the structure of their semantic environment. However, group differences were observed, with an early peak in the autistic group’s clustering coefficient (how closely connected groups of words are), followed by a sharp decline. Moreover, across each network metric, we found that autistic children had reduced small-world structure relative to non-autistic toddlers. Thus, group differences indicate that, although autistic children are learning from their semantic environment, they may be processing their semantic environment differently, the language input to which they are exposed differs relative to non-autistic children, or a combination of the two.

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10. Hagen A, Klein AM, Bögels SM, van Steensel B. Family Functioning in Families of Children with an Anxiety Disorder, with and without Autism Spectrum Disorder. J Autism Dev Disord;2025 (Jun 3)

This study compared family functioning among families of children with anxiety disorders, with and without autism spectrum disorder (ASD), and typically developing children. We evaluated (1) group differences in family functioning, (2) changes in family functioning following child-focused cognitive behavioral therapy for anxiety, and (3) whether pre-treatment family functioning predicted anxiety reduction. Participants were 264 children (aged 7-18 years) and their parents (251 mothers and 172 fathers). Groups consisted of children with anxiety disorders without ASD (n = 95), children with both conditions (n = 79), and typically developing children (n = 90). Children and parents completed the Family Functioning Scale, which assesses relational functioning and system maintenance. As expected, families of children with both anxiety disorders and ASD reported lower relational functioning and higher system maintenance than controls. System maintenance was also higher in these families than in the anxiety-only group (per both parents). Unexpectedly, the anxiety-only group did not differ from the control group. Additionally, cognitive behavioral therapy did not improve family functioning in either clinical group, nor did pre-treatment family functioning predict anxiety reductions. Families of children with both anxiety and ASD showed poorer family functioning than both other groups. Future research should examine whether these challenges stem from their co-occurrence or are specific to ASD.

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11. Hali S, Yao X, Hao G, Jin ZL, Fu K, Li Y, Wang L, Yoo H, La H, Park C, Hong K, Shin CY, Woo DH, Han C, Jin X, Zhu S, Zou W, Kim NH, Kim KP, Zhang LW, Han DW. Differentiation Defect Into GABAergic Neurons in Cerebral Organoids From Autism Patients. CNS Neurosci Ther;2025 (Jun);31(6):e70449.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social communication and behaviors. While previous studies using animal models have substantially expanded our knowledge about ASD, the lack of an appropriate human model system that accurately recapitulates the human-specific pathophysiology of ASD hinders the precise understanding of its etiology and the development of effective therapies. This study aims to replicate pathological phenotypes in cerebral organoids derived from idiopathic ASD patients and to conduct proof-of-concept research for the development of ASD therapeutics. METHODS: We conducted an in vitro disease modeling study using cerebral organoids derived from three idiopathic ASD patients. Additionally, we performed organoid-based phenotypic drug screening to identify potential therapeutic compounds that could ameliorate the phenotypes observed in cerebral organoids derived from idiopathic ASD patients. RESULTS: Here we show that cerebral organoids derived from idiopathic ASD patients display malformation of the ventricular zones and impaired early neuronal differentiation. Through organoid-based phenotypic drug screening, we successfully generated cerebral organoids with normal tissue architecture in which the delayed neuronal differentiation could also be accelerated. Notably, cerebral organoids from ASD patients exhibited a reduced number of GABAergic neurons compared to healthy controls, resulting in an imbalance in the excitatory and inhibitory neuron ratio. The differentiation defects into GABAergic neurons in patient-derived cerebral organoids could be rescued by treating with either IGF1 or Gabapentin, a GABA agonist. CONCLUSIONS: Our findings provide a framework for utilizing patient-derived cerebral organoids in the development of personalized pharmaceutical treatment for ASD.

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12. He S, Jing F, Ren H, Xiao Y, Chen XS, Tang R, Qiu Y, Zeng J, Gao T, Huang J. Exploring emotions and perspectives of families with autism spectrum disorder individuals on sports participation: a case study on Weibo using machine learning method. BMC Sports Sci Med Rehabil;2025 (Jun 3);17(1):141.

BACKGROUND: Physical activity is known to have numerous benefits for individuals with autism spectrum disorder (ASD). Understanding family sentiments towards ASD sports participation is crucial for developing interventions that promote physical activity. This study aimed to explore the sentiments of families regarding sports participation for individuals with ASD using longitudinal data from Weibo, a popular Chinese social media platform. OBJECTIVE: This study investigates family sentiments and attitudes toward sports participation by ASD individuals, leveraging longitudinal data from Sina Weibo and machine learning-based sentiment analysis. METHODS: We collected Weibo posts containing the keyword « autism » from January 2020 to April 2023, filtered for sports‑related content, and divided the dataset into ten four‑month intervals. Using SnowNLP’s Naive Bayes-based sentiment classifier, we labeled each post as positive or negative and analyzed temporal trends. RESULTS: Positive sentiments toward sports participation far outnumbered negative sentiments, and the proportion of supportive posts increased steadily over the study period, reflecting growing recognition of sports’ role in enhancing well‑being and development among ASD individuals. CONCLUSION: Families of ASD individuals increasingly acknowledge the multifaceted benefits of physical activity. These insights can guide the design of targeted interventions and inclusive sports programs, ultimately fostering greater participation and improving quality of life within the ASD community.

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13. Henriksen MG, Nielsen KM, Mottron L, Nordgaard J. Autism in schizophrenia and its original link to self-disorder: returning a borrowed concept. Lancet Psychiatry;2025 (Jun 3)

Autism was introduced by Eugen Bleuler in 1910 as a defining feature of schizophrenia, and it remained so for 80 years. However, the concept was borrowed by Leo Kanner and Hans Asperger to describe another condition (infantile autism) and eventually awareness of autistic features in schizophrenia declined. Today, autistic features are by default considered indicative of autism spectrum disorder, and patients with schizophrenia, who exhibit autistic features, risk being misdiagnosed with autism spectrum disorder and receiving inadequate treatment. To aid differential diagnosis and treatment, it is important to rediscover what autism in schizophrenia is, and how it differs from autism spectrum disorder. We present a reading of the seminal works that shaped the understanding of autism in schizophrenia and extract four key insights: autistic features are common in schizophrenia; autistic features are found both in behaviours and experiences; autism in schizophrenia can be defined as a frail immersion in the lifeworld, manifesting as a pervasive inability to take for granted what others consider matter of fact; and autism is hypothesised to be caused by self-disorder. Contemporary psychopathological research corroborates the idea that autism is caused by self-disorder, a concept that could substantially aid differential diagnostic resources.

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14. Hessl D, Wang JY, Espinal G, Santos E, Tassone F, Hagerman RJ, Rivera SM. Longitudinal Analysis of Neuroradiological Biomarkers for Fragile X-Associated Tremor/Ataxia Syndrome and Implications for Clinical Trials. Ann Neurol;2025 (Jun 3)

OBJECTIVE: The objective of this study was to show the capacity of structural brain magnetic resonance imaging (MRI) measures to serve as monitoring biomarkers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). METHODS: From 2 longitudinal studies of male FMR1 premutation carriers, 2 brain MRI scans were selected from each participant, collected within a period of 2 years (12 healthy controls, 17 carriers without FXTAS, and 51 carriers with FXTAS; all men, ages 40 to 80 years), along with clinical measurements and FMR1 cytosine-guanine-guanine (CGG) repeat numbers. Candidate MRI biomarkers included whole brain white matter hyperintensity (WMH) and cerebellar, brainstem, and whole brain volumes. RESULTS: In the FXTAS group, mixed-effects models demonstrated significant volume loss across an average interval of 1.32 years for the whole brain, cerebellum and brain stem volumes, and significant increases in WMH, with large magnitude effects for whole brain and WMH volumes. All MRI measures showed deterioration with advancing FXTAS stage, with the strongest pattern shown in WMH volume. CGG repeat number showed significant nonlinear associations with all 4 brain MRI metrics, with mid-range CGG repeat carriers evidencing the worst brain atrophy and WMHs. INTERPRETATION: Structural brain MRI measurements, especially those capturing white matter deterioration, are correlated with FMR1 premutation size of CGG repeat length and sensitive to FXTAS disease progression across a relatively short interval of less than 2 years, making them potentially suitable as surrogate end points for clinical trials. ANN NEUROL 2025.

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15. Hollocks MJ, McQuaid GA, Lee NR, Wallace GL. Cognitive Flexibility Mediates the Associations Between Perceived Stress, Social Camouflaging and Mental Health Challenges in Autistic Adults. Autism Res;2025 (Jun 3)

Autistic people are at an elevated risk of experiencing co-occurring anxiety and depression. The contributors to this are likely multifaceted and complex and remain poorly understood. Cognitive flexibility, social camouflaging, and perceived stress provide useful indices of the interacting neurocognitive, behavioral, and environmental factors that have been associated with anxiety and depression in autistic individuals. Here, we test if cognitive flexibility, as the factor most closely related to individual differences in thinking styles, mediates the relationships between social camouflaging, perceived stress, and anxiety/depression. This study included 806 autistic individuals aged between 18 and 83 years (Mean age = 40.2), recruited through the Research Match service of the Simons Powering Autism Research (SPARK) participant registry. Participants completed an online battery of questionnaires measuring cognitive and social flexibility, social camouflaging, perceived stress, anxiety, and depression. Parallel mediation analyses were used to test the mediating effect of cognitive and social flexibility. Across separate parallel mediation analyses, cognitive flexibility was found to significantly mediate the relationships between both social camouflaging and perceived stress with anxiety and depression. This was contrasted with social flexibility, which showed a lower magnitude mediating effect for perceived stress and no mediating effect of social camouflaging. Cognitive flexibility plays an important mediating role between the impact of both perceived stress and social camouflaging on greater symptoms of both anxiety and depression in autistic adults.

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16. Iannuzzo F, Fernandez CS, Mangiapane R, Profilio L, Turiaco F, Lombardo C, Silvestri MC, Mento C, Carpita B, Dell’Osso L, Anna Muscatello MR, Bruno A. Autistic traits and experience and attitude toward the body: an investigation in a sample of Italian female patients with eating disorders. J Psychiatr Res;2025 (Aug);188:271-275.

OBJECTIVES: the present study aims to explore possible associations between autistic traits and the experience and attitude toward the body in female patients affected by eating disorders. METHODS: Participants with diagnosis of EDs as defined by the DSM-5TR were recruited between January and June 2023. Adult Autism Subthreshold (ADAS) Spectrum and Body Attitudes Test (BAT) were used to explore the presence of autistic traits and the alteration in body attitude. RESULTS: 44 female patients have been included in the study. The most represented ADAS Spectrum domains were « Empathy » and « Hyper-and hyporeactivity to sensory input ». Forward stepwise regression analysis indicated that BAT « Negative appreciation of body size » factor was predicted (R(2) = .311; R-squared adjusted = .277; F = 9.241; p < .0001) by ADAS Spectrum "Inflexibility" (p = .006) and "Verbal communication" (p = .038) domains, BAT "Lack of familiarity with one's own body" factor was predicted (R(2) = .587; R-squared adjusted = .566; F = 29.092; p < .0001) by ADAS Spectrum "Non-Verbal communication" (p < .0001) and "Hyper- and hyporeactivity to sensory input" (p = .001) domains, and BAT "General body dissatisfaction" factor was predicted (R(2) = .290; R-squared adjusted = .273; F = 17.181; p < .0001) by ADAS Spectrum "Non-Verbal communication" (p < .0001) domain. CONCLUSIONS: the current work highlights that several core autistic traits, as assessed by the ADAS Spectrum, may be predictive of alterations in body image, knowledge, and satisfaction. The observed association between subthreshold autism and eating disorders supports the hypothesis that EDs could be one of the possible psychopathological trajectories of a neurodevelopmental disorder rooted in autism spectrum.

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17. İletmiş G, Yaman GB. Prevalence of misophonia in patients with bipolar disorder: its relationship with autism spectrum symptoms and emotion regulation skills in comparison to a control group. Nord J Psychiatry;2025 (Jun 3):1-10.

INTRODUCTION: The aim of this study is to determine the prevalence of misophonia in patients diagnosed with bipolar disorder (BD), examine its relationship with autism spectrum symptoms and emotion regulation skills, and compare it with a healthy control group. METHODS: The study included 105 patients diagnosed with BD in remission for at least three months and 105 age-, gender-, and education-matched healthy controls. All participants completed the sociodemographic data form, Hamilton Depression Rating Scale, Young Mania Rating Scale, Revised Amsterdam Misophonia Scale, Emotion Regulation Skills Questionnaire, and Autism Spectrum Quotient. RESULTS: Misophonia symptoms were statistically significantly more prevalent in the healthy control group (63.8%) than in the BD group (48.6%) (p = 0.026). Among BD patients with misophonia symptoms, a history of suicide attempts and higher autistic traits were statistically significantly more common (p = 0.026, p = 0.003, respectively). No statistically significant relationship was found between the severity of misophonia and autism traits (r = 0.200; p = 0.159) or emotion regulation skills (r = -0.178; p = 0.210). Multivariate regression analyses identified suicide attempt history and autistic traits as significant predictors of misophonia severity. CONCLUSION: Misophonia symptoms were more prevalent in control group, contrary to our hypothesis. BD patients exhibited pronounced emotion regulation deficits, which worsened with increased autistic traits. Misophonia symptoms were statistically significantly associated with adverse psychiatric outcomes in BD patients. These findings highlight the importance of assessing misophonia, emotion regulation, and autistic traits collectively in clinical settings, and suggest that addressing misophonia symptoms in treatment planning may enhance patient functioning.

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18. Jain A, Dhir N, Prabha PK, Raja A, Sharma AR, Kaundal T, Charan S, Bhatia A, Banerjee D, Saikia B, Zohmangaihi D, Goyal MK, Medhi B, Prakash A. Adenylyl Cyclase Activator: Forskolin Mediates CREB ser133 Phosphorylation in the Hippocampus, Alleviates Autism-Like Deficits in a Valproic Acid Model of Wistar Rats. J Neurosci Res;2025 (Jun);103(6):e70049.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits, restricted interest, and repetitive behaviors. The prevalence is higher in males (4:1). FDA-approved drugs, Aripiprazole, and risperidone, only target comorbid conditions and have significant side effects. Dysregulation in cAMP-responsive element-binding protein (CREB) signaling is reported in autistic individuals. Forskolin is traditionally used in Ayurvedic medicine with lesser side effects. It is a potent adenylyl cyclase (AC) activator, increases intracellular cyclic adenosine monophosphate (cAMP) levels, thereby activating the protein kinase A (PKA)/CREB pathway with clinically proven benefits as an anticancer, anti-asthmatic, and in metabolic disorder, and crosses the blood-brain-barrier (BBB) junction. The present study aimed to investigate the impact of Forskolin and sought to explore the role of estrogen beta (ERβ/ESR2) receptors in a valproic acid (VPA) model of ASD. Pregnant Wistar rats received VPA or an equal volume of saline on gestational day (GD) 12.5. From postnatal day (PND) 23, male and female rats were divided separately into control, VPA, risperidone, and Forskolin (10-30 mg/kg) groups. Systemic administration of Forskolin ameliorated anxiety, social deficit, repetitive behavior, spatial recognition memory, motor coordination, gastrointestinal (GIT) motility, brain edema, and BBB permeability in a dose-dependent manner. Moreover, chronic Forskolin treatment significantly alleviated VPA-induced neuronal damage in the prefrontal cortex (PFC), hippocampus (HC), and cerebellum, and increased the intracellular CREB ser133 protein phosphorylation. Forskolin upregulated the mRNA expression of CREB signaling, which was altered by prenatal VPA administration. Our findings indicate that Forskolin provides neuroprotection through CREB signaling, suggesting its therapeutic potential for ASD.

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19. Jeong J, Yoo HJ, An JY, Jeong S. Dysregulated RNA Binding Proteins and Alternative Splicing: Emerging Roles in Autism Spectrum Disorder. Mol Cells;2025 (Jun 3):100237.

Dysregulation of gene expression can lead to abnormal brain function, with alternative splicing playing a crucial role in proper brain development. Emerging evidence suggests that dysregulated RNA-binding proteins (RBPs) contribute to aberrant splicing patterns, disrupting neuronal processes and increasing susceptibility to neurodevelopmental disorders such as autism spectrum disorder (ASD). Understanding how misregulated RBPs alter splicing mechanisms is crucial for elucidating their role in ASD pathogenesis. Additionally, this knowledge is essential for developing targeted therapeutic strategies aimed at correcting splicing-related abnormalities. This review highlights recent advancements in our understanding of the interplay between RBPs and alternative splicing in ASD and explores promising RNAtargeting therapeutic approaches.

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20. K VRP, Bindu CH, Devi KR. An interpretable deep learning approach for autism spectrum disorder detection in children using NASNet-mobile. Biomed Phys Eng Express;2025 (Jun 3);11(4)

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder featuring impaired social interactions and communication abilities engaging the individuals in a restrictive or repetitive behaviour. Though incurable early detection and intervention can reduce the severity of symptoms. Structural magnetic resonance imaging (sMRI) can improve diagnostic accuracy, facilitating early diagnosis to offer more tailored care. With the emergence of deep learning (DL), neuroimaging-based approaches for ASD diagnosis have been focused. However, many existing models lack interpretability of their decisions for diagnosis. The prime objective of this work is to perform ASD classification precisely and to interpret the classification process in a better way so as to discern the major features that are appropriate for the prediction of disorder. The proposed model employs neural architecture search network – mobile(NASNet-Mobile) model for ASD detection, which is integrated with an explainable artificial intelligence (XAI) technique called local interpretable model-agnostic explanations (LIME) for increased transparency of ASD classification. The model is trained on sMRI images of two age groups taken from autism brain imaging data exchange-I (ABIDE-I) dataset. The proposed model yielded accuracy of 0.9607, F1-score of 0.9614, specificity of 0.9774, sensitivity of 0.9451, negative predicted value (NPV) of 0.9429, positive predicted value (PPV) of 0.9783 and the diagnostic odds ratio of 745.59 for 2 to 11 years age group compared to 12 to 18 years group. These results are superior compared to other state of the art models Inception v3 and SqueezeNet.

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21. Kamp-Becker I, Poustka L. Media Consumption by Preschool Children: The Risk of Autism and Developmental Disorders. Dtsch Arztebl Int;2025 (Aug 8)(Forthcoming)

BACKGROUND: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by impaired social communication and the presence of restricted, repetitive patterns of behavior, typically manifesting in early childhood. The rising prevalence of ASD has been discussed in relation to increased media consumption. METHODS: A selective literature search was conducted in the Medline database on the topics of media consumption and mental disorders, particularly autism, in preschool children. Seven systematic reviews and meta-analyses and 36 original studies were included in the analysis. RESULTS: The findings across studies consistently demonstrated that media consumption in preschool children was associated with deficits in language and cognitive development (adjusted odds ratio [aOR] 1.67-2.28) and was a risk factor for the development of emotional, behavioral, and developmental disorders (aOR: 1.34-3.06). Symptoms consistent with ASD were also found to be associated with increased media consumption (OR 1.97, 95% confidence interval [1.30; 3.00]). However, these observed effects were consistently identified in the context of multiple other risk factors for mental health problems-such as low socioeconomic status, a family history of mental disorders, or parental stress-which mediated these effects, either directly or indirectly. Intervention studies showed that reducing media consumption, combined with an increase in constructive parent-child interactions, led to a reduction in symptom severity. CONCLUSION: In the context of additional risk factors, increased media consumption in young children is associated with atypical or delayed development. The extent of developmental disorders can be reduced through targeted support for parents. When risk factors are present, it is therefore essential to educate parents and implement preventive measures to promote the long-term healthy development of children.

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22. Keen DL. Enhancing the Well-Being of Older Adults and Young Adults with Developmental Disabilities Through an Intergenerational Community Garden: Participatory Action Research. Glob Qual Nurs Res;2025 (Jan-Dec);12:23333936251342017.

Loneliness and lack of purpose have a negative impact on well-being for young adults with developmental disabilities (DD) and older adults. Young adults with DD often lack meaningful relationships. While some aspects of well-being remain stable as a person ages, a sense of purpose may decline as life roles diminish. The purpose of this research was to discover ways enhance well-being in adults with DD and older adults through intergenerational interaction. A participatory action research approach was used with qualitative methods that included semi-structured interviews with four young adults with DD and five older adults. Participant observation and field notes were employed to enhance the rigor of the study. A community garden was the environment for intergenerational activities. Through thematic analysis of the data, five themes of well-being were constructed: engagement, positive relationships, accomplishment, meaning and purpose, and positive emotion with elements specific to adults with DD and older adults. The study revealed ways to enlist the wisdom and knowledge of older adults to enhance the well-being of young adults with DD and consequently enhance the well-being of the older adult as well. Implications of this study include employing social capital to improve well-being through synergistic relationships.

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23. Lee JH, Park YM, Han K, Park YB, Kim BS, Jung JH, Nam GE. Intellectual developmental disability and all-cause and cause-specific mortality among individuals with type 2 diabetes mellitus. Diabetes Res Clin Pract;2025 (Jun 3);226:112305.

AIMS: Individuals with intellectual developmental disabilities (IDD) face unique challenges in managing type 2 diabetes mellitus (T2DM), but evidence on their impact on mortality is limited. This study assessed the association between IDD and mortality in T2DM using nationwide Korean data. METHODS: A retrospective cohort of 2,522,244 individuals with T2DM who underwent health screenings through the Korea National Health Insurance Service 2015-2016 was analyzed. IDD presence and severity were evaluated, and mortality risks were estimated using multivariable Cox proportional hazards models. RESULTS: Among a total population, 0.22 % (n = 5,627) had IDD. Over a six-year median follow-up, 201,153 deaths (7.98 %) occurred. Individuals with IDD had significantly higher risk of all-cause mortality (hazard ratio [HR] 3.40, 95 % CI: 3.14-3.68), with greater severity correlating with higher risk (P < 0.001). Cause-specific mortality risks were significantly elevated for cardiovascular (HR 3.77, 95 % CI: 3.12-4.55), cancer (HR 1.52, 95 % CI: 1.24-1.86), and respiratory diseases (HR 7.71, 95 % CI: 6.27-9.48). Younger individuals showed stronger associations. CONCLUSIONS: Individuals with T2DM and IDD, particularly those with severe IDD, have a significantly higher mortality risk. Tailored healthcare strategies and enhanced social support are urgently required to reduce disparities in this vulnerable population.

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24. Li P, Men S, Patel PJ, Saleem K, Zhong P, Tam KW, Feng J, Yan Z. Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene Smarcc2 and its Rescue by Histone Deacetylase Inhibition. bioRxiv;2025 (Jun 3)

SMARCC2 , which encodes BAF170, a core subunit of chromatin remodeling BAF complex, is one of the top-ranking risk genes for autism spectrum disorder (ASD). However, the mechanisms linking SMARCC2 haploinsufficiency to ASD remain poorly understood. Genome-wide RNA-seq analysis revealed that SMARCC2 was significantly diminished in iPSC-derived neurons from idiopathic ASD patients. ChIP-seq of SMARCC2 demonstrated its binding to many other ASD risk genes involved in transcriptional regulation. Smarcc2 deficiency in prefrontal cortex (PFC) of adolescent mice led to impaired working memory, with largely intact social and anxiety-like behaviors. Significant downregulation of genes enriched in synaptic transmission were found in PFC of S marcc2 -deficient mice by RNA-seq and qPCR profiling. In parallel, electrophysiological recordings uncovered the significant impairment of GABAergic and glutamatergic synaptic currents in S marcc2 -deficient PFC pyramidal neurons. Smarcc2 bound to HDAC2, and Smarcc2 deficiency led to the reduced global histone acetylation and H3K9ac enrichment at synaptic gene Slc1a3 (EAAT1), Slc6a1 (GAT1), and Slc32a1 (VGAT) promoters. Treatment of S marcc2 -deficient mice with romidepsin, a class I HDAC inhibitor, restored histone acetylation, working memory and some synaptic gene expression. These findings highlight the critical role of Smarcc2 in regulating cognitive and synaptic function, suggesting that targeting HDAC could alleviate deficits in Smarcc2-associated neurodevelopmental disorders.

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25. Nocera VG, Wozencroft AJ, Coe DP. Methodologies, perspectives and strategies to promote holistic assessment of health and activity behaviours in youth with developmental disabilities: a narrative review. BMJ Open Sport Exerc Med;2025;11(2):e002194.

Physical activity is known to have multiple health benefits for youth with developmental disabilities (DDs). Individuals with DDs are at risk for adverse health-related outcomes. Limited research has shown that the prevalence of youth meeting recommendations for physical activity is low. However, there are challenges in assessing physical activity and achieving adequate compliance in this population, which may lead to inaccurate data. Factors that play a role in the ability of an individual to participate in adequate physical activity to meet recommendations include the ability to perform motor skills and the functional capacity to pursue and engage in a variety of activities. The purpose of this narrative review is to describe the current practices, barriers and strategies associated with physical activity, motor proficiency and metabolic assessments in youth with DDs. This paper elucidates barriers to physical activity, motor proficiency and metabolic assessments in youth with DDs while providing strategies to aid in the successful administration of protocols. Evidence-based and anecdotal evidence provided in this paper supports the use of the following strategies to aid in assessment: peer modelling, parent support, individualised behaviour techniques, positive reinforcement and the use of social narratives. Future work in this area should continue to (a) critically evaluate, implement and develop assessment tools and protocols in youth with DDs and (b) establish reference data specific to the target population.

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26. Noel JP, Balzani E, Acerbi L, Benson J, Savin C, Angelaki DE. A common computational and neural anomaly across mouse models of autism. Nat Neurosci;2025 (Jun 3)

Computational psychiatry studies suggest that individuals with autism spectrum disorder (ASD) inflexibly update their expectations. Here we leveraged high-yield rodent psychophysics, extensive behavioral modeling and brain-wide single-cell extracellular recordings to assess whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, what neurophysiological features are shared across genotypes. Mice harboring mutations in Fmr1, Cntnap2 or Shank3B show a blunted update of priors during decision-making. Compared with mice that flexibly updated their priors, inflexible updating of priors was associated with a shift in the weighting of prior encoding from sensory to frontal cortices. Furthermore, frontal areas in mouse models of ASD showed more units encoding deviations from the animals’ long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings suggest that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.

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27. Pan R, Bi Y, Zhou S, Tian Z, Xu A. Association between anesthetics and autism spectrum disorder: from bench to bedside. J Anesth;2025 (Jun 2)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms of impaired social communication and stereotyped behaviors. While early-life exposure to anesthetics may increase the risk of ASD, anesthetics can also have therapeutic effects on ASD, potentially through mechanisms involving the N-methyl-D-aspartate (NMDA) receptor, gamma-aminobutyric acid (GABA)ergic, and µ-opioid receptor signaling pathways. Given that individuals with ASD often exhibit high levels of non-cooperation and poor communication abilities, they typically require deeper sedation during medical examinations, making the choice of anesthetics particularly critical. This article provides an overview about the effects and underlying mechanisms of various anesthetics with ASD, aiming to assist anesthesiologists in implementing anesthesia management for ASD patients more scientifically.

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28. Shaked-Ashkenazi S, Bar I, Oliver-Aronson L, Horesh D, Eden S, Golan O. Short communication: Psychological distress in autistic and non-autistic Israeli children exposed to war and terrorism. J Psychiatr Res;2025 (Aug);188:266-270.

Exposure to war and terrorism is linked to psychological distress, impacting both those directly involved and their relatives. Children, who are especially vulnerable due to their developing cognitive and emotional capacities, are significantly affected. However, there is a lack of research on the psychological effects of war and terrorism on autistic children. This study aims to fill this gap by examining the psychological distress experienced by Israeli autistic children compared to non-autistic children following the October 7th, 2023, terrorism attack and subsequent war. The study involved 228 parents of children aged 4-11 (134 autistic, 94 non-autistic) who completed online questionnaires regarding their child’s exposure to war events and anxiety levels. Results showed that nearly all children were exposed to traumatic events. While non-autistic children had higher exposure rates, autistic children exhibited greater anxiety aggravation, particularly concerning physical injury, panic attacks, and agoraphobia. These findings highlight the unique vulnerability of autistic children during severe traumatic events and emphasize the urgent need for early detection, diagnosis, and specialized treatment of trauma in autistic children in conflict-affected regions.

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29. Singh J, Santosh P. Molecular Insights into Neurological Regression with a Focus on Rett Syndrome-A Narrative Review. Int J Mol Sci;2025 (Jun 3);26(11)

Rett syndrome (RTT) is a multisystem neurological disorder. Pathogenic changes in the MECP2 gene that codes for methyl-CpG-binding protein 2 (MeCP2) in RTT lead to a loss of previously established motor and cognitive skills. Unravelling the mechanisms of neurological regression in RTT is complex, due to multiple components of the neural epigenome being affected. Most evidence has primarily focused on deciphering the complexity of transcriptional machinery at the molecular level. Little attention has been paid to how epigenetic changes across the neural epigenome in RTT lead to neurological regression. In this narrative review, we examine how pathogenic changes in MECP2 can disrupt the balance of the RTT neural epigenome and lead to neurological regression. Environmental and genetic factors can disturb the balance of the neural epigenome in RTT, modifying the onset of neurological regression. Methylation changes across the RTT neural epigenome and the consequent genotoxic stress cause neurons to regress into a senescent state. These changes influence the brain as it matures and lead to the emergence of specific symptoms at different developmental periods. Future work could focus on epidrugs or epi-editing approaches that may theoretically help to restore the epigenetic imbalance and thereby minimise the impact of genotoxic stress on the RTT neural epigenome.

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30. Smith JV, Nevill R, DeGuzman PB, Menezes M, Mazurek MO. Sociodemographic Factors Associated with Autistic Youth’s Psychotherapy Service Use. Adm Policy Ment Health;2025 (Jun 3)

Autistic youth have a high co-occurrence of mental health challenges and a resultant high need for mental health treatment. However, they experience mental health service disparities compared to non-autistic youth. Social determinants of health (SDH) may contribute to mental health service disparities among autistic youth, yet this has not been previously examined. Therefore, the present study utilized a validated composite of children’s SDH to examine whether autistic youth with better SDH were more likely to use psychotherapy services compared to those with poor SDH using state-level records of insurance billing claims data (2019 All-Payer Claims Database). 700 autistic youth with a co-occurring mental health condition were included in analyses. One or more claim records for psychotherapy CPT codes were used as indicators of psychotherapy service use. SDH was assessed using the Childhood Opportunity Index, a continuous composite measure of neighborhood SDH. The predictive effect of SDH on psychotherapy use were examined, while examining covariates of insurance type and age. Approximately 70% of the sample did not use any psychotherapy services. Inconsistent with findings from non-autistic samples, autistic youth’s SDH did not predict their likelihood of using psychotherapy services; rather, those with low and high opportunity alike did not access psychotherapy. Age increased the likelihood, and using Medicaid decreased the likelihood of psychotherapy service use. These results may highlight the compounded barriers to psychotherapy that autistic youth may experience, including the paucity of mental health providers who accept Medicaid and accept autistic youth clients.

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31. Wang R, Ren Z, Li Y. The effect of sulforaphane on autism spectrum disorder: systematic review and meta-analysis. Excli j;2025;24:542-557.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder lacking effective treatments. This systematic review and meta-analysis assesses the efficacy and safety of sulforaphane (SFN) for ASD. Eight databases were searched from inception to September 2024, identifying six randomized controlled trials for inclusion. Efficacy outcomes included ASD symptoms measured by the mean difference (MD) or standardized mean difference (SMD), while safety outcomes included adverse events measured by relative risk. Risk of bias was assessed using the Cochrane tool, and evidence certainty was evaluated via the Grade of Recommendations Assessment Development and Evaluation (GRADE). Results showed that SFN significantly improved total symptoms (SMD = -0.27, 95 % confidence interval (CI), -0.42, -0.12), aberrant behavior (SMD = -0.43, 95 % CI, -0.66, -0.19), hyperactivity (SMD = -0.58, 95 % CI, -1.03, -0.13), social interaction (SMD = -0.43, 95 % CI, -0.59, -0.27), social communication (SMD = -0.24, 95 % CI, -0.35, – 0.12), and restricted and repetitive behaviors (RRB) (SMD = -0.16, 95 % CI, -0.31, -0.00). Effects on irritability, anxiety, sensory sensitivity, total social skills, social awareness, social cognition, and social motivation were not statistically significant. Adverse events were similar between intervention and control groups. In conclusion, SFN shows potential in improving ASD symptoms without significant adverse effects. However, results should be interpreted cautiously due to potential influences from assessment tools, outcome assessors, and treatment duration. Further research is needed to confirm the long-term efficacy and safety of SFN for ASD.

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